GMMID: genetically modified mice information database.

Genetically engineered mouse models (GEMMs) are vital for elucidating gene function and disease mechanisms. An overwhelming number of GEMM lines have been generated, but endeavors to collect and organize the information of these GEMMs are seriously lagging behind. Only a few databases are developed for the information of current GEMMs, and these databases lack biological descriptions of allele compositions, which poses a challenge for nonexperts in mouse genetics to interpret the genetic information of these mice. Moreover, these databases usually do not provide information on human diseases related to the GEMM, which hinders the dissemination of the insights the GEMM provides as a human disease model. To address these issues, we developed an algorithm to annotate all the allele compositions that have been reported with Python programming and have developed the genetically modified mice information database (GMMID; http://www.gmmid.cn), a user-friendly database that integrates information on GEMMs and related diseases from various databases, including National Center for Biotechnology Information, Mouse Genome Informatics, Online Mendelian Inheritance in Man, International Mouse Phenotyping Consortium, and Jax lab. GMMID provides comprehensive genetic information on >70 055 alleles, 65 520 allele compositions, and ∼4000 diseases, along with biologically meaningful descriptions of alleles and allele combinations. Furthermore, it provides spatiotemporal visualization of anatomical tissues mentioned in these descriptions, shown alongside the allele compositions. Compared to existing mouse databases, GMMID considers the needs of researchers across different disciplines and presents obscure genetic information in an intuitive and easy-to-understand format. It facilitates users in obtaining complete genetic information more efficiently, making it an essential resource for cross-disciplinary researchers. Database URL: http://www.gmmid.cn.

Mechanical Properties and Microanalytical Study of Concrete Reinforced with Blended Corn Straw and Scrap Steel Fibers.

Fiber concrete exhibits superior performance in various aspects compared to plain concrete and has been widely researched and applied worldwide. However, many industrially made fibers are expensive, and their cost has to be considered before use; thus, it would be economically valuable to find inexpensive fibers with excellent properties to make fiber concrete. Rural areas have many rich straw resources to be disposed of; at the same time, the rapid development of the automobile industry has introduced a large number of used tires containing steel wire with a very low reuse rate. These two low-cost materials can be processed to make fibers, making the study of mechanical properties regarding their incorporation into concrete practically significant for reducing the cost of fiber concrete. Based on this, a three-factor, three-level orthogonal test was conducted to investigate the effects of different dosages of corn straw fibers and scrap steel fibers, as well as the water-cement ratio, on the mechanical properties of concrete. The optimum level of each factor for blended straw-waste-steel-fiber concrete with different mechanical properties was obtained using the polar and ANOVA methods. It was found that the compressive strength, splitting tensile strength, flexural strength, and impact resistance of the specimens after fiber dosing were better than those of plain concrete specimens with the same water-cement ratio. The maximum improvement was 14.96% in cubic compressive strength, 42.90% in tensile strength, and 16.30% in flexural strength, while the maximum improvement in impact energy consumption at the final crack was 228.03%. Combined with SEM microanalysis, the two fibers formed a stronger whole with the C-S-H gel. When the specimen was subjected to load, the two fibers were able to withstand part of the load, thus enhancing the load-bearing capacity. Finally, the optimal mix ratio of blended straw-scrap-steel-fiber concrete was determined to be 0.8% corn straw fibers by volume, 0.6% scrap steel fibers by volume, and a 0.45 water-cement ratio by combining the weights of the levels of each factor under its four different mechanical properties through hierarchical analysis. This analysis of mechanical properties provides a reference for practical applications in future projects.

Predicting anti-tumor efficacy of multi-functional nanomedicine on decellularized hepatocellular carcinoma-on-a-chip.

Traditional hepatocellular carcinoma-chip models lack the cell structure and microenvironments necessary for high pathophysiological correlation, leading to low accuracy in predicting drug efficacy and high production costs. This study proposed a decellularized hepatocellular carcinoma-on-a-chip model to screen anti-tumor nanomedicine. In this model, human hepatocellular carcinoma (HepG2) and human normal liver cells (L02) were co-cultured on a three-dimensional (3D) decellularized extracellular matrix (dECM) in vitro to mimic the tumor microenvironments of human hepatocellular carcinoma in vivo. Additionally, a smart nanomedicine was developed by encapsulating doxorubicin (DOX) into the ferric oxide (Fe3O4)-incorporated liposome nanovesicle (NLV/Fe+DOX). NLV/Fe+DOX selectively killed 78.59% ± 6.78% of HepG2 cells through targeted delivery and synergistic chemo-chemodynamic-photothermal therapies, while the viability of surrounding L02 cells on the chip model retained high, at over 90.0%. The drug efficacy tested using this unique chip model correlated well with the results of cellular and animal experiments. In summary, our proposed hepatocellular carcinoma-chip model is a low-cost yet accurate drug-testing platform with significant potential for drug screening.

Structural basis for the transport and substrate selection of human urate transporter 1.

High serum urate levels are the major risk factor for gout. URAT1, the primary transporter for urate absorption in the kidneys, is well known as an anti-hyperuricemia drug target. However, the clinical application of URAT1-targeted drugs is limited because of their low specificity and severe side effects. The lack of structural information impedes elucidation of the transport mechanism and the development of new drugs. Here, we present the cryoelectron microscopy (cryo-EM) structures of human URAT1(R477S), its complex with urate, and its closely related homolog OAT4. URAT1(R477S) and OAT4 exhibit major facilitator superfamily (MFS) folds with outward- and inward-open conformations, respectively. Structural comparison reveals a 30° rotation between the N-terminal and C-terminal domains, supporting an alternating access mechanism. A conserved arginine (OAT4-Arg473/URAT1-Arg477) is found to be essential for chloride-mediated inhibition. The URAT1(R477S)-urate complex reveals the specificity of urate recognition. Taken together, our study promotes our understanding of the transport mechanism and substrate selection of URAT1.

Lead Bromide Complex in Tri-n-Octylphosphine Oxide Matrix with Bright Photoluminance and Exceptional Thermoplasticity.

Metal halide materials have recently drawn increasing research interest for their excellent opto-electronic properties and structural diversity, but their resulting rigid structures render them brittle and poor formability during manufacturing. Here we demonstrate a thermoplastic luminant hybrid lead halide solid by integrating lead bromide complex into tri-n-octylphosphine oxide (TOPO) matrix. The construction of the hybrid materials can be achieved by a simple dissolution process, in which TOPO molecules act as the solvents and ligands to yield the monodispersed clusters. The combination of these functional units enables the near-room-temperature melt-processing of the materials into targeted geometry by simple molding or printing techniques, which offer possibilities for fluorescent writing inks with outstanding self-healing capacity to physical damage. The intermarriage between metal halide clusters with functional molecules expands the range of practical applications for hybrid metal halide materials.

Effects of high-quality protein supplementation on cardiovascular risk factors in individuals with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Uncertainties still existed about the effect of high-quality protein supplementation on cardiovascular disease (CVD) risk factors, although high-quality proteins such as soy and milk proteins have proposed to be beneficial for cardiometabolic health. METHODS: A systematic search in PubMed, Web of Science, Cochrane Library, Scopus, and Embase was conducted to quantify the impact of high-quality protein on CVD risk factors. RESULTS: 63 RCTs on 4 types of high-quality protein including soy protein, milk protein, whey, and casein were evaluated. Soy protein supplementation decreased systolic blood pressure (SBP, -1.42 [-2.68, -0.17] mmHg), total cholesterol (TC, -0.18 [-0.30, -0.07] mmol/L), and low-density lipoprotein cholesterol (LDL-C, -0.16 [-0.27, -0.05] mmol/L). Milk protein supplementation decreased SBP (-2.30 [-3.45, -1.15] mmHg) and total cholesterol (-0.27 [-0.51, -0.03] mmol/L). Whey supplementation decreased SBP (-2.20 [-3.89, -0.51] mmHg), diastolic blood pressure (DBP, -1.07 [-1.98, -0.16] mmHg), triglycerides (-0.10 [-0.17, -0.03] mmol/L), TC (-0.18 [-0.35, -0.01] mmol/L), LDL-C (-0.09 [-0.16, -0.01] mmol/L) and fasting blood insulin (FBI, -2.02 [-3.75, -0.29] pmol/L). Casein supplementation decreased SBP (-4.10 [-8.05, -0.14] mmHg). In the pooled analysis of four high-quality proteins, differential effects were seen in individuals with different health status. In hypertensive individuals, high-quality proteins decreased both SBP (-2.69 [-3.50, -1.87] mmHg) and DBP (-1.34 [-2.09, -0.60] mmHg). In overweight/obese individuals, high-quality proteins improved SBP (-1.40 [-2.22, -0.59] mmHg), DBP (-2.59 [-3.20, -1.98] mmHg), triglycerides (-0.09 [-0.15, -0.02] mmol/L), TC (-0.14 [-0.22, -0.05] mmol/L), LDL-C (-0.12 [-0.16, -0.07] mmol/L), and HDL-C levels (0.02 [0.01, 0.04] mmol/L). According to the benefits on CVD risks factors, whey ranked top for improving cardiometabolic health in hypertensive or overweight/obese individuals. CONCLUSION: Our study supports a beneficial role of high-quality protein supplementation to reduce CVD risk factors. Further studies are still warranted to investigate the effects of different high-quality proteins on CVD risks in individuals with cardiometabolic disorders.

Regulatory Mechanism of Proanthocyanidins in Grape Peels Using vvi-miR828a and Its Target Gene VvMYBPA1.

Anthocyanins and proanthocyanidins are considered to be essential secondary metabolites in grapes and are used to regulate metabolic processes, while miRNAs are involved in their synthesis of anthocyanins and proanthocyanidins to regulate metabolic processes. The present research work was carried out to investigate the underlying regulatory mechanism of target genes in the grape cultivars 'Italia' and 'Benitaka'. miRNA and transnscriptomic sequencing technology were employed to characterize both the profiles of miRNAs and the transcripts of grape peels at 10 and 11 weeks post flowering (10 wpf and 11 wpf). The results revealed that the expression level of vvi-miR828a in 'Italia' at 10 and 11 wpf was significantly higher than that in 'Benitaka'. miRNA-seq analysis predicted MYBPA1 to be the target gene of vvi-miR828a. In transcriptome analysis, the expression level of the VvMYBPA1 gene in 'Benitaka' was significantly higher than that in 'Italia'; in addition, the TPM values (expression levels) of VvMYBPA1 and miR828a also showed an evident negative correlation. The determination of the proanthocyanidin (PA) content in 'Italia' and 'Benitaka' peels at 11 wpf demonstrated that the PA content of 'Benitaka' was significantly higher than that of 'Italia'. The outcomes of RT-qRCR analysis exhibited that the expression levels of the VdPAL, VdCHS, VdCHI, VdDFR, VdMYB5b, VdANR, and VdMYBPA1 genes related anthocyanin and proanthocyanidin pathways were reduced, while the expression levels of all of the above genes were increased after the transient expression of the VvMYBPA1 vector into grape leaves. The results of the transient overexpression experiment of vvi-miR828a before the veraison period of strawberry fruits showed that vvi-miR828a can significantly slow down the coloration of strawberries. The vvi-miR828a negatively regulates the accumulation of proanthocyanidins in grape fruits by inhibiting the expression of VvMYBPA1.

DEKR-SPrior: An Efficient Bottom-Up Keypoint Detection Model for Accurate Pod Phenotyping in Soybean.

The pod and seed counts are important yield-related traits in soybean. High-precision soybean breeders face the major challenge of accurately phenotyping the number of pods and seeds in a high-throughput manner. Recent advances in artificial intelligence, especially deep learning (DL) models, have provided new avenues for high-throughput phenotyping of crop traits with increased precision. However, the available DL models are less effective for phenotyping pods that are densely packed and overlap in in situ soybean plants; thus, accurate phenotyping of the number of pods and seeds in soybean plant is an important challenge. To address this challenge, the present study proposed a bottom-up model, DEKR-SPrior (disentangled keypoint regression with structural prior), for in situ soybean pod phenotyping, which considers soybean pods and seeds analogous to human people and joints, respectively. In particular, we designed a novel structural prior (SPrior) module that utilizes cosine similarity to improve feature discrimination, which is important for differentiating closely located seeds from highly similar seeds. To further enhance the accuracy of pod location, we cropped full-sized images into smaller and high-resolution subimages for analysis. The results on our image datasets revealed that DEKR-SPrior outperformed multiple bottom-up models, viz., Lightweight-OpenPose, OpenPose, HigherHRNet, and DEKR, reducing the mean absolute error from 25.81 (in the original DEKR) to 21.11 (in the DEKR-SPrior) in pod phenotyping. This paper demonstrated the great potential of DEKR-SPrior for plant phenotyping, and we hope that DEKR-SPrior will help future plant phenotyping.

The Effect of Bifidobacterium animalis subsp. lactis MN-Gup on Glucose Metabolism, Gut Microbiota, and Their Metabolites in Type 2 Diabetic Mice.

Probiotics have garnered increasing attention as a potential therapeutic approach for type 2 diabetes mellitus (T2DM). Previous studies have confirmed that Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) could stimulate the secretion of glucagon-like peptide-1 (GLP-1) in NCI-H716 cells, but whether MN-Gup has a hypoglycemic effect on T2DM in vivo remains unclear. In this study, a T2DM mouse model was constructed, with a high-fat diet and streptozotocin in mice, to investigate the effect of MN-Gup on diabetes. Then, different doses of MN-Gup (2 × 109 CFU/kg, 1 × 1010 CFU/kg) were gavaged for 6 weeks to investigate the effect of MN-Gup on glucose metabolism and its potential mechanisms. The results showed that a high-dose of MN-Gup significantly reduced the fasting blood glucose (FBG) levels and homeostasis model assessment-insulin resistance (HOMA-IR) of T2DM mice compared to the other groups. In addition, there were significant increases in the short-chain fatty acids (SCFAs), especially acetate, and GLP-1 levels in the MN-Gup group. MN-Gup increased the relative abundance of Bifidobacterium and decreased the number of Escherichia-Shigella and Staphylococcus. Moreover, the correlation analysis revealed that Bifidobacterium demonstrated a significant positive correlation with GLP-1 and a negative correlation with the incremental AUC. In summary, this study demonstrates that Bifidobacterium animalis subsp. lactis MN-Gup has significant hypoglycemic effects in T2DM mice and can modulate the gut microbiota, promoting the secretion of SCFAs and GLP-1.

Facile Recycling of Waste Biomass for Preparation of Hierarchical Porous Carbon with High-Performance Electromagnetic Wave Absorption.

Hierarchical-porous-structured materials have been widely used in the field of electromagnetic wave (EMW) absorption, playing a critical role in minimizing EMW interference and pollution. High-quality EMW absorbers, characterized by a lower thickness, lighter weight, wider absorption band, and stronger absorption capacity, have been instrumental in reducing damage and preventing malfunctions in the automotive and aviation industries. The utilization of discarded nut shells through recycling can not only alleviate environmental problems but relieve resource constraints. Herein, a facile method for the preparation of hierarchical porous biomass carbon derived from abandoned Xanthoceras Sorbifolium Bunge Shell (XSS) biomass was developed for high-performance EMW absorption. The porous structures of XSS biochar were studied by using different levels of the K2CO3 activator and simple carbonization. The effect of K2CO3 on the EMW parameters, including the complex permittivity, complex permeability, polarization relaxation, and impedance matching, was analyzed. The best EMW absorption performance of the XSS biochar was observed at a mass ratio of activator-to-biomass of 2:1. A minimum reflection loss (RLmin) of -38.9 dB was achieved at 9.12 GHz, and a maximum effective absorption bandwidth (EABmax) of up to 3.28 GHz (14.72~18.0 GHz) could be obtained at a 1.8 mm thickness. These results demonstrated that hierarchical porous XSS carbon was prepared successfully. Simultaneously, the prepared XSS biochar was confirmed as a potential and powerfully attractive EMW-absorbing material. The proposal also provided a simple strategy for the development of a green, low-cost, and sustainable biochar as a lightweight high-performance absorbing material.

Foxo1 is an iron-responsive transcriptional factor regulating systemic iron homeostasis.

The liver plays a crucial role in maintaining systemic iron homeostasis by secreting hepcidin, which is essential for coordinating iron levels in the body. Imbalances in iron homeostasis are associated with various clinical disorders related to iron deficiency or iron overload. Despite the clinical significance, the mechanisms underlying how hepatocytes sense extracellular iron levels to regulate hepcidin synthesis and iron storage are not fully understood. In this study, we identified Foxo1, a well-known regulator of macronutrient metabolism, that translocates to the nucleus of hepatocytes in response to high-iron feeding, holo-transferrin, and BMP6 treatment. Furthermore, Foxo1 plays a crucial role in mediating hepcidin induction in response to both iron and BMP signals by directly interacting with evolutionally conserved Foxo binding sites within the hepcidin promoter region. These binding sites were found to colocalize with Smad-binding sites. To investigate the physiological relevance of Foxo1 in iron metabolism, we generated mice with hepatocyte-specific deletion of Foxo1. These mice exhibited reduced hepatic hepcidin expression and serum hepcidin levels, accompanied by elevated serum iron and liver non-heme iron concentrations. Moreover, high-iron diet further exacerbated these abnormalities in iron metabolism in mice lacking hepatic Foxo1. Conversely, hepatocyte-specific Foxo1 overexpression increased hepatic hepcidin expression and serum hepcidin levels, thereby ameliorating iron overload in a murine model of hereditary hemochromatosis (Hfe-/- mice). In summary, our study identifies Foxo1 is a critical regulator of hepcidin and systemic iron homeostasis. Targeting Foxo1 may offer therapeutic opportunities for managing conditions associated with aberrant iron metabolism.

Development and evaluation of a risk prediction tool for risk-adapted screening of colorectal cancer in China.

Risk prediction tools for colorectal cancer (CRC) have potential to improve the efficiency of population-based screening by facilitating risk-adapted strategies. However, such an applicable tool has yet to be established in the Chinese population. In this study, a risk score was created using data from the China Kadoorie Biobank (CKB), a nationwide cohort study of 409,854 eligible participants. Diagnostic performance of the risk score was evaluated in an independent CRC screening programme, which included 91,575 participants who accepted colonoscopy at designed hospitals in Zhejiang Province, China. Over a median follow-up of 11.1 years, 3136 CRC cases were documented in the CKB. A risk score was created based on nine questionnaire-derived variables, showing moderate discrimination for 10-year CRC risk (C-statistic = 0.68, 95 % CI: 0.67-0.69). In the CRC screening programme, the detection rates of CRC were 0.25 %, 0.82 %, and 1.93 % in low-risk (score <6), intermediate-risk (score: 6-19), and high-risk (score >19) groups, respectively. The newly developed score exhibited a C-statistic of 0.65 (95 % CI: 0.63-0.66), surpassing the widely adopted tools such as the Asia-Pacific Colorectal Screening (APCS), modified APCS, and Korean Colorectal Screening scores (all C-statistics = 0.60). In conclusion, we developed a novel risk prediction tool that is useful to identify individuals at high risk of CRC. A user-friendly online calculator was also constructed to encourage broader adoption of the tool.

Distributional Characteristics Analysis of Allergens in Patients with Allergic Rhinitis in Southern Fujian Province, China.

Background: Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa. However, few studies focus on the distributional characteristics of allergens in AR patients in Southern Fujian Province, China. Methods: A skin prick test (SPT) was performed and eight common allergens including Dermatophagoides farinae (Df), Dermatophagoides pteronyssinus (Dpt), weeds, animal dander, molds, cockroaches, and mangoes were chosen. Results: The positive reactions rate to the allergens was 65.79% in 6689 patients in Southern Fujian Province. Positive reactions to Df and Dpt had a negative association with age, whereas positive reactions to cockroach and weed had a positive association with age. A linear trend analysis demonstrated a significant positive relationship between positive reactions to various allergens from 2016 to 2019. Positive reactions to Df and Dpt were both correlated with the season. Positive reactions to Df, Dpt, cockroach and weed were related to disease duration and positive reactions to cockroach were correlated with city residence. Multivariate analysis revealed that male positive reactions gradually decreased with age (≤ 60), in contrast to female (≤ 60) positive reactions. Statistical difference was observed between the genders with regard to AR incidence from 2016 to 2019. The positive rate of skin tests was highest in summer in men, whereas in women it was lowest in summer. The gender composition ratios of positive cases in Xiamen, Zhangzhou, and Quanzhou cities differed significantly. The proportion of patients with positive reactions to the allergens in the three cities decreased with age. The highest proportions of patients with positive reactions all occurred during summer in the three cities. Furthermore, there were statistically significant differences in the age composition ratios across the seasons. Conclusion: This study analyzed the distributional characteristics of AR allergens in Southern Fujian Province, China. These findings will inform specific immunotherapy for AR patients.

Residual networks without pooling layers improve the accuracy of genomic predictions.

KEY MESSAGE: Residual neural network genomic selection is the first GS algorithm to reach 35 layers, and its prediction accuracy surpasses previous algorithms. With the decrease in DNA sequencing costs and the development of deep learning, phenotype prediction accuracy by genomic selection (GS) continues to improve. Residual networks, a widely validated deep learning technique, are introduced to deep learning for GS. Since each locus has a different weighted impact on the phenotype, strided convolutions are more suitable for GS problems than pooling layers. Through the above technological innovations, we propose a GS deep learning algorithm, residual neural network for genomic selection (ResGS). ResGS is the first neural network to reach 35 layers in GS. In 15 cases from four public data, the prediction accuracy of ResGS is higher than that of ridge-regression best linear unbiased prediction, support vector regression, random forest, gradient boosting regressor, and deep neural network genomic prediction in most cases. ResGS performs well in dealing with gene-environment interaction. Phenotypes from other environments are imported into ResGS along with genetic data. The prediction results are much better than just providing genetic data as input, which demonstrates the effectiveness of GS multi-modal learning. Standard deviation is recommended as an auxiliary GS evaluation metric, which could improve the distribution of predicted results. Deep learning for GS, such as ResGS, is becoming more accurate in phenotype prediction.

Average grain size evaluation using scattering-induced attenuation of coda waves.

Grain size is one of the key microstructural factors affecting the mechanical properties of polycrystalline metal materials. In this study, a novel method for grain size evaluation using ultrasonic coda waves is proposed. Different from conventional bulk wave methods that require a point-by-point scanning of the structure, the proposed method allows for a rapid evaluation of the average grain size of the whole part from a single inspection location using one-pass testing data. A piecewise energy attenuation function dealing with different attenuation mechanisms is proposed to obtain the effective attenuation coefficient of coda waves. A power-law model is constructed to correlate the effective attenuation coefficient with the average grain size. Ultrasonic testing on nickel-based superalloy plate specimens with different average grain sizes is performed for model calibration and method verification. The applicability and robustness of the proposed method are further validated using a realistic turbine disk specimen with an irregular shape and non-uniform grain sizes. Results show that the proposed method yields a reliable and accurate estimation of the average grain size with a maximum relative error less than 20 %.

Study on the Bonding Performance of BFRP Bars with Seawater Sand Concrete.

A total of 66 sets of pullout specimens were prepared to investigate the bonding properties of basalt fiber-reinforced polymer reinforcement (hereinafter referred to as BFRP) with seawater sand concrete (hereinafter referred to as SSC). The volume dosages of mono-doped glass fibers and mono-doped polypropylene fibers were 0.1%, 0.2%, and 0.3%; the total volume dosage was set to be constant at 0.3%; and the doping ratios of the hybrid fibers were 1:2, 1:1, and 2:1. The effect on the bonding performance of BFRP reinforcement with SSC was studied on the condition of the diameter D of the BFRP reinforcement being 12 mm; the bond length of SSC being 3D, 5D, and 7D; and the surface characteristics of the reinforcement being sandblasted and threaded. The research showed that due to internal cracks in the matrix, salt crystals in the pores, chloride salts with high brittleness and expansion, as well as sulfate corrosion products such as "Frederick salts" in SSC, the concrete became brittle, resulting in more brittle splitting failures during the pullout test. Doped fibers can increase the ductility effect of concrete, but the bonding effect between the threaded fiber reinforcement and the SSC was not as good as that of the sandblasting group. When the bond length was 5D, the bonding effect between the BFRP reinforcement and SSC was the best, and the bonding performance of the experimental group with doped fibers was better than that of the threaded group. Finally, by combining the ascending segment of the Malvar model with the descending segment of the improved BPE model, a constitutive relationship model suitable for the bond-slip curve between BFRP reinforcement and SSC was fitted, which laid a theoretical foundation for future research on SSC.

Enhancement and modulation of valley polarization in Janus CrSSe with internal and external electric fields.

The valley polarization, induced by the magnetic proximity effect, in monolayer transition metal dichalcogenides (TMDCs), has attracted significant attention due to the intriguing fundamental physics. However, the enhancement and modulation of valley polarization for real device applications is still a challenge. Here, using first-principles calculations we investigate the valley polarization properties of monolayer TMDCs CrS2 and CrSe2 and how to enhance the valley polarization by constructing Janus CrSSe (with an internal electric field) and modulate the polarization in CrSSe by applying external electric fields. Janus CrSSe exhibits inversion symmetry breaking, internal electric field, spin-orbit coupling, and compelling spin-valley coupling. A magnetic substrate of the MnO2 monolayer can induce a modest magnetic moment in CrSe2, CrSe2, and CrSSe. Notably, the Janus structure with an internal electric field has a much larger valley p compared with its non-Janus counterparts. Moreover, the strength of valley polarization can be further modulated by applying external electric fields. These findings suggest that Janus materials hold promise for designing and developing advanced valleytronic devices.

Study on the Damage of Fiber-Reinforced Seawater Sea Sand Concrete by Freezing and Thawing of Seawater.

The use of seawater and sea sand as replacements for fresh water and river sand in the preparation of seawater and sea sand concrete can effectively address issues such as high transportation costs, extended construction periods, and resource wastage. Nevertheless, in northern coastal areas, the problem of concrete durability in the complex and changing marine environment is more prominent. Research on the durability of seawater sea sand concrete is beneficial to the widening of its application range. To investigate the impact of glass fiber (GF) and polyvinyl alcohol fiber (PVA) with different blending methods on the seawater freeze-thaw resistance of seawater sea sand concrete (SSC), corresponding specimens were prepared, and seawater freeze-thaw cycling tests were conducted. By adopting the slow-freezing method and combining macro-structure and micro-morphology, the damage mechanism and the deterioration law of fiber-reinforced SSC under seawater freezing and thawing were investigated. The results indicate that, macroscopically, the incorporation of GF and PVA can effectively mitigate the damage to the matrix and reduce the effects of external erosive substances on the rate of strength loss, the rate of mass loss, and the relative dynamic elastic modulus. After 75 cycles, the SSC with a total volume doping of 0.3% and a blending ratio of 1:1 showed a 41.23% and 27.55% reduction in mass loss and strength loss, respectively, and a 29.9% improvement in relative dynamic elastic modulus compared with the basic group. Microscopic analysis reveals that the combined effect of freezing and expansion forces, the expansive substances generated by seawater intrusion into the interior of the matrix, and salt crystallization all weaken the bond between aggregate and mortar, leading to accelerated deterioration of the concrete. The incorporation of fibers enables the matrix to become denser and improves its crack-resistant properties, resulting in a better durability than that of the basic group. The damage prediction model established by the NSGM(1,N) model of gray system theory exhibits high accuracy and is suitable for long-term prediction, accurately predicting the damage of seawater sea sand concrete under seawater freeze-thaw coupling.

Human umbilical cord-derived mesenchymal stromal cells improve myocardial fibrosis and restore miRNA-133a expression in diabetic cardiomyopathy.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a serious health-threatening complication of diabetes mellitus characterized by myocardial fibrosis and abnormal cardiac function. Human umbilical cord mesenchymal stromal cells (hUC-MSCs) are a potential therapeutic tool for DCM and myocardial fibrosis via mechanisms such as the regulation of microRNA (miRNA) expression and inflammation. It remains unclear, however, whether hUC-MSC therapy has beneficial effects on cardiac function following different durations of diabetes and which mechanistic aspects of DCM are modulated by hUC-MSC administration at different stages of its development. This study aimed to investigate the therapeutic effects of intravenous administration of hUC-MSCs on DCM following different durations of hyperglycemia in an experimental male model of diabetes and to determine the effects on expression of candidate miRNAs, target mRNA and inflammatory mediators. METHODS: A male mouse model of diabetes was induced by multiple low-dose streptozotocin injections. The effects on severity of DCM of intravenous injections of hUC-MSCs and saline two weeks previously were compared at 10 and 18 weeks after diabetes induction. At both time-points, biochemical assays, echocardiography, histopathology, polymerase chain reaction (PCR), immunohistochemistry and enzyme-linked immunosorbent assays (ELISA) were used to analyze blood glucose, body weight, cardiac structure and function, degree of myocardial fibrosis and expression of fibrosis-related mRNA, miRNA and inflammatory mediators. RESULTS: Saline-treated diabetic male mice had impaired cardiac function and increased cardiac fibrosis after 10 and 18 weeks of diabetes. At both time-points, cardiac dysfunction and fibrosis were improved in hUC-MSC-treated mice. Pro-fibrotic indicators (α-SMA, collagen I, collagen III, Smad3, Smad4) were reduced and anti-fibrotic mediators (FGF-1, miRNA-133a) were increased in hearts of diabetic animals receiving hUC-MSCs compared to saline. Increased blood levels of pro-inflammatory cytokines (IL-6, TNF, IL-1ß) and increased cardiac expression of IL-6 were also observed in saline-treated mice and were reduced by hUC-MSCs at both time-points, but to a lesser degree at 18 weeks. CONCLUSION: Intravenous injection of hUC-MSCs ameliorated key functional and structural features of DCM in male mice with diabetes of shorter and longer duration. Mechanistically, these effects were associated with restoration of intra-myocardial expression of miRNA-133a and its target mRNA COL1AI as well as suppression of systemic and localized inflammatory mediators.

Deciphering microglial activation and neuronal apoptosis post­traumatic brain injury: The role of TYROBP in inflammation regulation networks.

Traumatic Brain Injury (TBI) represents a significant public health challenge. Recovery from brain injury necessitates the collaborative efforts of various resident neural cells, predominantly microglia. The present study analyzed rat and mouse RNA expression micro­arrays, high­throughput RNA sequencing and single­cell sequencing data sourced from public databases. To construct an inflammation regulation network around TYRO protein tyrosine kinase­binding protein (TYROBP), to evaluate the role of TYROBP in cell death after TBI. These findings indicate that following TBI, neurons predominantly communicate with one another through the CXC chemokine ligand (CXCL) and CC chemokine ligand (CCL) signaling pathways, employing a paracrine mechanism to activate microglia. These activated microglia intensify the pathological progression of brain injury by releasing factors such as tumor necrosis factor α (TNF­α), vascular endothelial growth factor and transforming growth factor ß via the NF­κB pathway. Cells co­culture experiments demonstrated that neurons, impaired by mechanical injury, interact with microglia through non­contact mechanisms. Activated microglia secrete cytokines, including TNF­α, CXCL­8 and CCL2, which trigger an inflammatory response and facilitate neuronal apoptosis. TYROBP gene knockout in microglia was demonstrated to reduce this interaction and reduce neuronal cell apoptosis rates.