Co-expression network analysis and identification of core genes in the interaction between wheat and Puccinia striiformis f. sp. tritici.

The epidemic of stripe rust, caused by the pathogen Puccinia striiformis f. sp. tritici (Pst), would reduce wheat (Triticum aestivum) yields seriously. Traditional experimental methods are difficult to discover the interaction between wheat and Pst. Multi-omics data analysis provides a new idea for efficiently mining the interactions between host and pathogen. We used 140 wheat-Pst RNA-Seq data to screen for differentially expressed genes (DEGs) between low susceptibility and high susceptibility samples, and carried out Gene Ontology (GO) enrichment analysis. Based on this, we constructed a gene co-expression network, identified the core genes and interacted gene pairs from the conservative modules. Finally, we checked the distribution of Nucleotide-binding and leucine-rich repeat (NLR) genes in the co-expression network and drew the wheat NLR gene co-expression network. In order to provide accessible information for related researchers, we built a web-based visualization platform to display the data. Based on the analysis, we found that resistance-related genes such as TaPR1, TaWRKY18 and HSP70 were highly expressed in the network. They were likely to be involved in the biological processes of Pst infecting wheat. This study can assist scholars in conducting studies on the pathogenesis and help to advance the investigation of wheat-Pst interaction patterns.

High-Temperature-Induced Differential Expression of miRNA Mediates Liver Inflammatory Response in Tsinling Lenok Trout (Brachymystax lenok tsinlingensis).

High-temperature stress poses a significant environmental challenge for aquatic organisms, including tsinling lenok trout (Brachymystax lenok tsinlingensis). This study aimed to investigate the role of microRNAs (miRNAs) in inducing liver inflammation in tsinling lenok trout under high-temperature stress. Tsinling lenok trout were exposed to high-temperature conditions (24 °C) for 8 h, and liver samples were collected for analysis. Through small RNA sequencing, we identified differentially expressed miRNAs in the liver of high-temperature-stressed tsinling lenok trout compared to the control group (maintained at 16 °C). Several miRNAs, including novel-m0105-5p and miR-8159-x, showed significant changes in expression levels. Additionally, we conducted bioinformatics analysis to explore the potential target genes of these differentially expressed miRNAs. Our findings revealed that these miRNA target genes are involved in inflammatory response pathways, such as NFKB1 and MAP3K5. The downregulation of novel-m0105-5p and miR-8159-x in the liver of high-temperature-stressed tsinling lenok trout suggests their role in regulating liver inflammatory responses. To validate this, we performed a dual-luciferase reporter assay to confirm the regulatory relationship between miRNAs and target genes. Our results demonstrated that novel-m0105-5p and miR-8159-x enhance the inflammatory response of hepatocytes by promoting the expression of NFKB1 and MAP3K5, respectively. In conclusion, our study provides evidence that high-temperature stress induces liver inflammation in tsinling lenok trout through dysregulation of miRNAs. Understanding the molecular mechanisms underlying the inflammatory response in tsinling lenok trout under high-temperature stress is crucial for developing strategies to mitigate the negative impacts of environmental stressors on fish health and aquaculture production.

Polymer Engineering Enables High Linear Capacity Fiber Electrodes by Microenvironment Regulation.

Unlike bulky and rigid traditional power systems, 1D fiber batteries possess appealing features such as flexibility and adaptability, which are promising for use in wearable electronic devices. However, the performance and energy density fiber batteries are limited by the contradiction between ionic transfer and robust structure of fiber electrodes. Herein, these problems are addressed via polymer engineering to regulate the microenvironment in electrodes, realizing high-linear-capacity thick fiber electrodes with excellent cycling performance. The porosity of the electrodes is regulated using polymer crosslink networks designed with various components, and lithium-ion transfer is optimized through ether-abundant polymer chains. Furthermore, reinforced covalent bonding with carbon nanotube networks is established based on the modified functional groups of polymer networks. The multiscale optimizations of the porous structure, ionic transportation, and covalent bonding network enhance the lithium-ion dynamics property and structural stability. Therefore, ultrahigh linear-capacity fiber electrodes (17.8 mAh m-1) can be fabricated on a large scale and exhibit excellent stability (92.8% after 800 cycles), demonstrating obvious superiority among the reported fiber electrodes. Moreover, this study highlights the high effectiveness of polymer regulation in fiber electrodes and offers new avenues for designing next-generation wearable energy-storage systems.

DeepSeeded: Volumetric Segmentation of Dense Cell Populations with a Cascade of Deep Neural Networks in Bacterial Biofilm Applications.

Accurate and automatic segmentation of individual cell instances in microscopy images is a vital step for quantifying the cellular attributes, which can subsequently lead to new discoveries in biomedical research. In recent years, data-driven deep learning techniques have shown promising results in this task. Despite the success of these techniques, many fail to accurately segment cells in microscopy images with high cell density and low signal-to-noise ratio. In this paper, we propose a novel 3D cell segmentation approach DeepSeeded, a cascaded deep learning architecture that estimates seeds for a classical seeded watershed segmentation. The cascaded architecture enhances the cell interior and border information using Euclidean distance transforms and detects the cell seeds by performing voxel-wise classification. The data-driven seed estimation process proposed here allows segmenting touching cell instances from a dense, intensity-inhomogeneous microscopy image volume. We demonstrate the performance of the proposed method in segmenting 3D microscopy images of a particularly dense cell population called bacterial biofilms. Experimental results on synthetic and two real biofilm datasets suggest that the proposed method leads to superior segmentation results when compared to state-of-the-art deep learning methods and a classical method.

Efficacy and safety of mesenchymal stem cell therapy for ovarian ageing in a mouse model.

BACKGROUND: Ovarian ageing is one of the major issues that impacts female fertility. Mesenchymal stem cell (MSC)-based therapy has made impressive progress in recent years. However, the efficacy and safety of MSCs, as nonautologous components, remain to be further verified. METHODS: Two common sources of MSCs, umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (AD-MSCs), were orthotopically transplanted into a mouse model of ovarian ageing to evaluate their therapeutic effects. The safety of the treatment was further evaluated, and RNA sequencing was performed to explore the underlying mechanisms involved. RESULTS: After orthotopic transplantation of MSCs into the ovary, the oestrous cycle, ovarian weight, number and proportion of primary follicles, granulosa cell proliferation, and angiogenesis were improved. The effects of AD-MSCs were superior to those of UC-MSCs in several indices, such as post-transplant granulosa cell proliferation, ovarian weight and angiogenesis. Moreover, the tumorigenesis, acute toxicity, immunogenicity and biodistribution of MSCs were evaluated, and both AD-MSCs and UC-MSCs were found to possess high safety profiles. Through RNA sequencing analysis, enhancement of the MAPK cascade was observed, and long-term effects were mainly linked to the activation of immune function. CONCLUSIONS: Orthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice.

High-enhancement photoluminescence of monolayer MoS2 in hybrid plasmonic systems.

Monolayer molybdenum disulfide (M o S 2) has a weak light-matter interaction due to ultrathin thickness, which limits its potential application in lasing action. In this study, we propose a hybrid structure consisting of a nanocavity and Au nanoparticles to enhance the photon emission efficiency of monolayer M o S 2. Numerical simulations show that photoluminescence (PL) emission is significantly enhanced by introducing localized surface plasmon resonance (LSPR) to the proposed structure. Furthermore, an exciton energy band system is proposed to elucidate the physical mechanism of the PL process. By optimizing the spacer thickness, a high Purcell enhancement factor of 95 can be achieved. The results provided by this work pave the way to improve the PL efficiency of two-dimensional (2D) material, which constitutes a significant step towards the development of nanodevices such as nanolasers and sensors.

High-Mobility Compensated Semimetals, Orbital Magnetization, and Umklapp Scattering in Bilayer Graphene Moiré Superlattices.

Twist-controlled moiré superlattices (MSs) have emerged as a versatile platform for realizing artificial systems with complex electronic spectra. The combination of Bernal-stacked bilayer graphene (BLG) and hexagonal boron nitride (hBN) can give rise to an interesting MS, which has recently featured a set of unexpected behaviors, such as unconventional ferroelectricity and the electronic ratchet effect. Yet, the understanding of the electronic properties of BLG/hBN MS has, at present, remained fairly limited. Here, we combine magneto-transport and low-energy sub-THz excitation to gain insights into the properties of this MS. We demonstrate that the alignment between BLG and hBN crystal lattices results in the emergence of compensated semimetals at some integer fillings of the moiré bands, separated by van Hove singularities where the Lifshitz transition occurs. A particularly pronounced semimetal develops when eight holes reside in the moiré unit cell, where coexisting high-mobility electron and hole systems feature strong magnetoresistance reaching 2350% already at B = 0.25 T. Next, by measuring the THz-driven Nernst effect in remote bands, we observe valley splitting, indicating an orbital magnetization characterized by a strongly enhanced effective gv-factor of 340. Finally, using THz photoresistance measurements, we show that the high-temperature conductivity of the BLG/hBN MS is limited by electron-electron umklapp processes. Our multifaceted analysis introduces THz-driven magnetotransport as a convenient tool to probe the band structure and interaction effects in van der Waals materials and provides a comprehensive understanding of the BLG/hBN MS.

"Flexible-strong" polylactic acid porous membrane via tailored polymerization degree of lactic acid side-chains grafting for passive daytime radiative cooler.

Aerogel possesses the advantages of high specific surface area, low density, and high porosity, which have shown great application in thermal regulation due to its efficient light scattering capability. However, traditional polymer-based aerogels have poor mechanical properties and lack ductility in outdoor applications, the cooling efficiency of the material is easily affected by damage during transportation, installation, and environmental factors. In this work, combining the porous nature of aerogels and the high ductility of membranes, a polylactic acid-based porous membrane cooler was developed by combining a regular honeycomb surface porous structure design and physical/chemical modification to enhance flexibility, using a simple non-solvent induced phase separation method. This porous membrane exhibits both super-flexibility (116 % elongation at break) and porous characteristics. It achieves a sub-ambient temperature decrease of 4-6 °C under direct sunlight. The optimized porous membrane demonstrates high solar reflectance (94 % of peak reflectivity, 90 % of average reflectivity) and strong infrared emissivity (96 % of peak emissivity, 91 % of average emissivity), it also maintains a solar peak reflectivity of 91 % under 100 % tensile strain and 1000 bending cycles, the cooler still maintains a cooling effect of 2-5 °C below ambient temperature. This work paves the way for developing mechanical flexible and strong radiative coolers for thermal regulation.

TransVFS: A spatio-temporal local-global transformer for vision-based force sensing during ultrasound-guided prostate biopsy.

Robot-assisted prostate biopsy is a new technology to diagnose prostate cancer, but its safety is influenced by the inability of robots to sense the tool-tissue interaction force accurately during biopsy. Recently, vision based force sensing (VFS) provides a potential solution to this issue by utilizing image sequences to infer the interaction force. However, the existing mainstream VFS methods cannot realize the accurate force sensing due to the adoption of convolutional or recurrent neural network to learn deformation from the optical images and some of these methods are not efficient especially when the recurrent convolutional operations are involved. This paper has presented a Transformer based VFS (TransVFS) method by leveraging ultrasound volume sequences acquired during prostate biopsy. The TransVFS method uses a spatio-temporal local-global Transformer to capture the local image details and the global dependency simultaneously to learn prostate deformations for force estimation. Distinctively, our method explores both the spatial and temporal attention mechanisms for image feature learning, thereby addressing the influence of the low ultrasound image resolution and the unclear prostate boundary on the accurate force estimation. Meanwhile, the two efficient local-global attention modules are introduced to reduce 4D spatio-temporal computation burden by utilizing the factorized spatio-temporal processing strategy, thereby facilitating the fast force estimation. Experiments on prostate phantom and beagle dogs show that our method significantly outperforms existing VFS methods and other spatio-temporal Transformer models. The TransVFS method surpasses the most competitive compared method ResNet3dGRU by providing the mean absolute errors of force estimation, i.e., 70.4 ± 60.0 millinewton (mN) vs 123.7 ± 95.6 mN, on the transabdominal ultrasound dataset of dogs.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

Comparison of treatment performance and microbial community evolution of typical dye wastewater by different combined processes.

The degradation of typical dye wastewater is a focus of research in the printing and dyeing industry. In this study, a combined micro-electrolysis and microbial treatment method was established to treat refractory dye wastewater, and the pivotal factors in the microbial treatment were optimized. In the series and coupled modes, the removal rates of chroma reached 98.75% and 92.50%, and the removal rates of chemical oxygen demand (COD) reached 96.17% and 82.29%, respectively. The high-throughput sequencing results showed that the microbial communities in the microbial system varied at different treatment stages. From the culture stage to the domestication stage, the dominant phylum was Proteobacteria; however, the community abundance of microorganisms decreased. A combination of micro-electrolysis and biological methods can alter the characteristics of the microbial community, increase the number of dominant phyla, and increase the abundance of microorganisms. The degradation effect of the series mode and the overall strengthening effect of micro-electrolysis on the microorganisms were better than those of the coupled mode. In actual wastewater, the maximum removal rates of chroma, COD, total nitrogen (TN), ammonia nitrogen (NH3-N), and total phosphorus (TP) are 97.50%, 98.90%, 94.35%, 93.95%, and 91.17%, respectively. Three-dimensional fluorescence spectrum analysis showed that microbial processes could significantly degrade fluorescent components in wastewater, and methanogenic active enzymes in anaerobic processes could continue to react. The combined process can realize the efficient treatment of toxic dye wastewater by reducing the toxicity of wastewater and efficiently degrading organic matter, which has important guiding significance for the treatment of refractory dye wastewater.

Single-cell RNA-seq reveals keratinocyte and fibroblast heterogeneity and their crosstalk via epithelial-mesenchymal transition in psoriasis.

The pathogenesis of psoriasis, a chronic inflammatory autoimmune skin disease with a high global prevalence, remains unclear. We performed a high-resolution single-cell RNA sequencing analysis of 94,759 cells from 13 samples, including those from psoriasis model mice and wild-type mice. We presented a single-cell atlas of the skin of imiquimod-induced mice with psoriasis and WT mice, especially the heterogeneity of keratinocytes and fibroblasts. More interestingly, we discovered that special keratinocyte subtypes and fibroblast subtypes could interact with each other through epithelial-mesenchymal transition and validated the results with drug verification. Moreover, we conducted a tentative exploration of the potential pathways involved and revealed that the IL-17 signalling pathway may be the most relevant pathway. Collectively, we revealed the full-cycle landscape of key cells associated with psoriasis and provided a more comprehensive understanding of the pathogenesis of psoriasis.

Abnormal upregulation of NUBP2 contributes to cancer progression in colorectal cancer.

Colorectal cancer (CRC), a digestive tract malignancy with high mortality and morbidity, lacks effective biomarkers for clinical prognosis due to its complex molecular pathogenesis. Nucleotide binding protein 2 (NUBP2) plays a vital role in the assembly of cytosolic Fe/S protein and has been implicated in cancer progression. In this study, we found that NUBP2 was highly expressed in CRC by TCGA database analysis. Subsequently, we verified the expression of NUBP2 in CRC tumor tissues and para-carcinoma tissues using IHC staining, and further investigated its association with clinicopathological parameters. In vitro cell experiments were conducted to assess the role of NUBP2 in CRC by evaluating cell proliferation, migration, and apoptosis upon NUBP2 dysregulation. Furthermore, we established a subcutaneous CRC model to evaluate the impact of NUBP2 on tumor growth in vivo. Additionally, we performed mechanistic exploration using a Human Phospho-Kinase Array-Membrane. Our results showed higher expression of NUBP2 in CRC tissues, which positively correlated with the pathological stage, indicating its involvement in tumor malignancy. Functional studies demonstrated that NUBP2 knockdown reduced cell proliferation, increased apoptosis, and impaired migration ability. Moreover, NUBP2 knockdown inhibited tumor growth in mice. We also observed significant changes in the phosphorylation level of GSK3ß upon NUBP2 knockdown or overexpression. Additionally, treatment with CHIR-99021 HCl, an inhibitor of GSK3ß, reversed the malignant phenotype induced by NUBP2 overexpression. Overall, this study elucidated the functional role of NUBP2 in CRC progression both in vitro and in vivo, providing insights into the molecular mechanisms underlying CRC and potential implications for targeted therapeutic strategies.

Immune-related long noncoding RNA zinc finger protein 710-AS1-201 promotes the metastasis and invasion of gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor of the gastrointestinal system. ZNF710 is a transcription factor (TF), and zinc finger protein 710 (ZNF710)-AS1-201 is an immune-related long noncoding RNA (lncRNA) that is upregulated in GC cells. AIM: To assess the correlation between ZNF710-AS1-201 and immune microenvironment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells. METHODS: We obtained data from The Cancer Genome Atlas and Wujin Hospital. We assessed cell growth, migration, invasion, and programmed cell death using cell counting kit-8, EdU, scratch, Transwell, and flow cytometry assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to identify the potential downstream targets of ZNF710-AS1-201. RESULTS: In GC tissues with low ZNF710-AS1-201 expression, immunoassays detected significant infiltration of various antitumor immune cells, such as memory CD8 T cells and activated CD4 T cells. In the low-expression group, the half-maximal inhibitory concentrations (IC50s) of 5-fluorouracil, cisplatin, gemcitabine, and trametinib were lower, whereas the IC50s of dasatinib and vorinostat were higher. The malignant degree of GC was higher and the stage was later in the high-expression group. Additionally, patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates. In vitro, the overexpression of ZNF710-AS1-201 greatly enhanced growth, metastasis, and infiltration while suppressing cell death in HGC-27 cells. In contrast, the reduced expression of ZNF710-AS1-201 greatly hindered cell growth, enhanced apoptosis, and suppressed the metastasis and invasion of MKN-45 cells. The expression changes in ZNF710 were significant, but the corresponding changes in isocitrate dehydrogenase-2, Semaphorin 4B, ARHGAP10, RGMB, hsa-miR-93-5p, and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201, as determined by qRT-PCR. CONCLUSION: Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells. It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC. Nevertheless, it is still necessary to determine the specific targets of the ZNF710 TF.

Discovery of RORγ Allosteric Fluorescent Probes and Their Application: Fluorescence Polarization, Screening, and Bioimaging.

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor MRL-871 (1), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes. Utilizing the preferred probe 12h, we established an efficient and cost-effective fluorescence polarization-based affinity assay for screening RORγ allosteric binders. By employing virtual screening in conjunction with this assay, 10 novel RORγ allosteric inhibitors were identified. The initial SAR studies focusing on the hit compound G381-0087 are also presented. The encouraging outcomes indicate that probe 12h possesses the potential to function as a powerful tool in facilitating the exploration of RORγ allosteric inhibitors and furthering understanding of RORγ function.

Dissecting the chiral recognition of TLR4/MD2 with Neoseptin-3 enantiomers by molecular dynamics simulations.

Toll-like receptor 4 (TLR4) is a pivotal innate immune recognition receptor that regulates intricate signaling pathways within the immune system. Neoseptin-3 (Neo-3), a recently identified small-molecule agonist for mouse TLR4/MD2, exhibits chiral recognition properties. Specifically, the L-enantiomer of Neo-3 (L-Neo-3) effectively activates the TLR4 signaling pathway, while D-Neo-3 fails to induce TLR4 activation. However, the underlying mechanism by which TLR4 enantioselectively recognizes Neo-3 enantiomers remains poorly understood. In this study, in silico simulations were performed to investigate the mechanism of chiral recognition of Neo-3 enantiomers by TLR4/MD2. Two L-Neo-3 molecules stably resided within the cavity of MD2 as a dimer, and the L-Neo-3 binding stabilized the (TLR4/MD2)2 dimerization state. However, the strong electrostatic repulsion between the hydrogen atoms on the chiral carbon of D-Neo-3 molecules caused the relative positions of two D-Neo-3 molecules to continuously shift during the simulation process, thus preventing the formation of D-Neo-3 dimer as well as their stable interactions with the surrounding residues in (TLR4/MD2)2. Considering that L-Neo-3 could not sustain a stable dimeric state in the bulk aqueous environment, it is unlikely that L-Neo-3 entered the cavity of MD2 as a dimeric unit. Umbrella sampling simulations revealed that the second L-Neo-3 molecule entering the cavity of MD2 exhibited a lower binding energy (-25.75 kcal mol-1) than that of the first L-Neo-3 molecule (-14.31 kcal mol-1). These results imply that two L-Neo-3 molecules enter the cavity of MD2 sequentially, with the binding of the first L-Neo-3 molecule facilitating the entry of the second one. This study dissects the binding process of Neo-3 enantiomers, offering a comprehensive understanding of the atomic-level mechanism underlying TLR4's chiral recognition of Neo-3 molecules.

KDELR2 promotes bone marrow mesenchymal stem cell osteogenic differentiation via GSK3ß/ß-catenin signaling pathway.

Nonunion is a challenging complication of fractures for the surgeon. Recently the Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum protein retention receptor 2 (KDELR2) has been found that involved in osteogenesis imperfecta. However, the exact mechanism is still unclear. In this study, we used lentivirus infection and mouse fracture model to investigate the role of KDELR2 in osteogenesis. Our results showed that KDELR2 knockdown inhibited the osteogenic differentiation of mBMSCs, whereas KDELR2 overexpression had the opposite effect. Furthermore, the levels of active-ß-catenin and phospho-GSK3ß (Ser9) were upregulated by KDELR2 overexpression and downregulated by KDELR2 knockdown. In the fracture model, mBMSCs overexpressing KDELR2 promoted healing. In conclusion, KDELR2 promotes the osteogenesis of mBMSCs by regulating the GSK3ß/ß-catenin signaling pathway.

Melatonin alleviates high temperature exposure induced fetal growth restriction via the gut-placenta-fetus axis in pregnant mice.

INTRODUCTION: Global warming augments the risk of adverse pregnancy outcomes in vulnerable expectant mothers. Pioneering investigations into heat stress (HS) have predominantly centered on its direct impact on reproductive functions, while the potential roles of gut microbiota, despite its significant influence on distant tissues, remain largely unexplored. Our understanding of deleterious mechanisms of HS and the development of effective intervention strategies to mitigate the detrimental impacts are still limited. OBJECTIVES: In this study, we aimed to explore the mechanisms by which melatonin targets gut microbes to alleviate HS-induced reproductive impairment. METHODS: We firstly evaluated the alleviating effects of melatonin supplementation on HS-induced reproductive disorder in pregnant mice. Microbial elimination and fecal microbiota transplantation (FMT) experiments were then conducted to confirm the efficacy of melatonin through regulating gut microbiota. Finally, a lipopolysaccharide (LPS)-challenged experiment was performed to verify the mechanism by which melatonin alleviates HS-induced reproductive impairment. RESULTS: Melatonin supplementation reinstated gut microbiota in heat stressed pregnant mice, reducing LPS-producing bacteria (Aliivibrio) and increasing beneficial butyrate-producing microflora (Butyricimonas). This restoration corresponded to decreased LPS along the maternal gut-placenta-fetus axis, accompanied by enhanced intestinal and placental barrier integrity, safeguarding fetuses from oxidative stress and inflammation, and ultimately improving fetal weight. Further pseudo-sterile and fecal microbiota transplantation trials confirmed that the protective effect of melatonin on fetal intrauterine growth under HS was partially dependent on gut microbiota. In LPS-challenged pregnant mice, melatonin administration mitigated placental barrier injury and abnormal angiogenesis via the inactivation of the TLR4/MAPK/VEGF signaling pathway, ultimately leading to enhanced nutrient transportation in the placenta and thereby improving the fetal weight. CONCLUSION: Melatonin alleviates HS-induced low fetal weight during pregnancy via the gut-placenta-fetus axis, the first time highlighting the gut microbiota as a novel intervention target to mitigate the detrimental impact of global temperature rise on vulnerable populations.

Dynamical characteristics of honeycomb two-dimensional gyroscopic metamaterials.

Suppression of noise and vibration suppression is important in various fields, such as the living environment, industrial development, and national defense and security. The bandgap properties of phononic crystal metamaterials provide an approach for controlling and eliminating harmful vibrations in equipment and noise in the environment. In this study, we used two types of two-dimensional honeycomb gyroscopic metamaterials: free and constrained. The dynamic equations of the two systems were established using angular momentum and Lagrange theorems. The dispersion relations of the two systems were obtained based on the Bloch theorem, and the influence of the gyroscope angular momentum or gyroscope speed on the dispersion relations was analyzed. Numerical simulations were conducted to analyze the wave propagation characteristics and polarization under different excitation conditions in a limited space for both types of metamaterial structures. The constrained-type and free-type metamaterials were compared, and the regularities of the dispersion relations and wave propagation characteristics by the gyroscope effect were summarized. This study provided a comprehensive and in-depth understanding of the bandgap and wave propagation properties of gyroscopic metamaterials and provided ideas for the design of bandgap modulation in metamaterials.