Nucleocytoplasmic trafficking and turnover mechanisms of BRASSINAZOLE RESISTANT1 in Arabidopsis thaliana.

Regulation of the nucleocytoplasmic trafficking of signaling components, especially transcription factors, is a key step of signal transduction in response to extracellular stimuli. In the brassinosteroid (BR) signal transduction pathway, transcription factors from the BRASSINAZOLE RESISTANT1 (BZR1) family are essential in mediating BR-regulated gene expression. The subcellular localization and transcriptional activity of BZR1 are tightly regulated by reversible protein phosphorylation; however, the underlying mechanism is not well understood. Here, we provide evidence that both BZR1 phosphorylation and dephosphorylation occur in the nucleus and that BR-regulated nuclear localization of BZR1 is independent from its interaction with, or dephosphorylation by, protein phosphatase 2A. Using a photoconvertible fluorescent protein, Kaede, as a living tag to distinguish newly synthesized BZR1 from existing BZR1, we demonstrated that BR treatment recruits cytosolic BZR1 to the nucleus, which could explain the fast responses of plants to BR. Additionally, we obtained evidence for two types of protein turnover mechanisms that regulate BZR1 abundance in plant cells: a BR- and 26S proteosome-independent constitutive degradation mechanism and a BR-activated 26S proteosome-dependent proteolytic mechanism. Finally, treating plant cells with inhibitors of 26S proteosome induces the nuclear localization and dephosphorylation of BZR1, even in the absence of BR signaling. Based on these results, we propose a model to explain how BR signaling regulates the nucleocytoplasmic trafficking and reversible phosphorylation of BZR1.

Melatonin enhances the sensitivity of colorectal cancer cells to 5-fluorouracil through the regulation of the miR-532-3p/ß-catenin pathway.

This research aimed to investigate whether melatonin affected sensitivity to 5-fluorouracil (5-FU) in colorectal cancer (CRC) as well as to show the underlying molecular mechanism. Melatonin and 5-FU were added to CRC cells at varying doses. The effect of melatonin on sensitivity to 5-FU was investigated by measuring cell activity and apoptosis, and the potential underlying mechanism was further explored by detecting miR-532-3p expression and the associated pathway proteins. Melatonin could suppress cell malignancy in SW480 and HCT116 cells. Melatonin also significantly promoted sensitivity to 5-FU in CRC cells. miR-532-3p expression was downregulated in CRC and was also markedly enhanced when treated with 1 mmol/L melatonin. The inhibitory ability of the co-cultured melatonin, 5-FU, and miR-532-3p inhibitor on SW480 and HCT116 cells was markedly diminished, and the IC50 value was significantly enhanced. Relative to the melatonin group, melatonin+miR-532-3p inhibitor markedly declined apoptosis rate. Bioinformatics analysis predicted the target of miR-532-3p. ß-catenin level presented obvious downregulation in the melatonin group, while it was notably upregulated in the co-culture group in relative to with that in the melatonin group. Overall, melatonin promotes sensitivity to 5-FU in CRC cells by regulating the miR-532-3p/ß-catenin pathway.

The fertilization process in Lithocarpus dealbatus (Fagaceae) and its implication on the sexual reproduction evolution of Fagales.

MAIN CONCLUSION: The pistillate flowers of Lithocarpus dealbatus show two pollen tube (PT) arresting sites (the style-joining and micropyle) within the pistil during the postpollination-prezygotic stage. The PT, arrested at the pre-ovule stage, enhanced PT competition allowing the most compatible PTs to enter the ovary to ensure the highest fertilization success. During the shift from animal pollination to wind pollination, plants require a series of changes in reproductive traits. The mode of pollination is striking labile in Fagaceae. Lithocarpus is insect pollinated and is closely related to wind-pollinated Quercus. Little is known about the sexual reproduction of Lithocarpus. This study aimed to reveal the sexual reproduction of Lithocarpus dealbatus and to explore the evolutionary pattern of the key sexual reproduction traits to better understand their possible role in labile pollination. We found that after pollination, L. dealbatus PTs grew slowly in the style reaching style-joining in mid-January of the second year; then PT growth was arrested at style-joining for four months. Only two to three PTs resumed growth in mid-May to reach the micropyle, where PT growth ceased for one month before one PT resumed growth and passed through the micropyle to the embryo sac. Fagaceae showed a generalized mating system. Vast pollen production, small-sized pollen grains, long stigmatic receptive time, and reduced perianth were compatible with beetle pollination syndrome, representing the plesiomorphic status in Fagaceae. A large stigmatic surface and dry pollen grains linked to wind pollination might be independently derived several times in fagaceous lineages. Beetle pollination syndrome can cope with the uncertainty of pollinators to ensure conspecific pollen capture, which represents pre-adaptation status and has a selective advantage when conditions change, favouring wind pollination. The arrest of the PT at style-joining is a unique mechanism in later derived fagaceous lineages to enhance PT competition and promote outcrossing.

Production of Sorbitol via Hydrogenation of Glucose over Ruthenium Coordinated with Amino Styrene-co-maleic Anhydride Polymer Encapsulated on Activated Carbon (Ru/ASMA@AC) Catalyst.

Sorbitol, a product primarily derived from glucose hydrogenation, has extensive applications in the pharmaceutical, chemical and other industries. Amino styrene-co-maleic anhydride polymer encapsulated on activated carbon (Ru/ASMA@AC) catalysts were developed for efficient glucose hydrogenation and were prepared and confined Ru by coordination with styrene-co-maleic anhydride polymer (ASMA). Through single-factor experiments, optimal conditions were determined to be 2.5 wt.% ruthenium loading and a catalyst usage of 1.5 g, 20% glucose solution at 130 °C, reaction pressure of 4.0 MPa, and a stirring speed of 600 rpm for 3 h. These conditions achieved a high glucose conversion rate of 99.68% and a sorbitol selectivity of 93.04%. Reaction kinetics testing proved that the hydrogenation of glucose catalyzed by Ru/ASMA@AC was a first-order reaction, with a reaction activation energy of 73.04 kJ/mol. Furthermore, the catalytic performance of the Ru/ASMA@AC and Ru/AC catalysts for glucose hydrogenation were compared and characterized by various detection methods. The Ru/ASMA@AC catalyst exhibited excellent stability after five cycles, whereas the traditional Ru/AC catalyst suffered from a 10% decrease in sorbitol yield after three cycles. These results suggest that the Ru/ASMA@AC catalyst is a more promising candidate for high-concentration glucose hydrogenation due to its high catalytic performance and superior stability.

FTO Alleviates CdCl2-Induced Apoptosis and Oxidative Stress via the AKT/Nrf2 Pathway in Bovine Granulosa Cells.

Cadmium (Cd) is a common environmental heavy metal contaminant of reproduction toxicity. Cd accumulation in animals leads to the damage of granulosa cells. However, its mechanism needs to be elucidated. This research found that treating granulosa cells with Cd resulted in reduced cell viability. The flow cytometry results showed that Cd increased the degree of apoptosis and level of superoxide anion (O2-) in granulosa cells. Further analysis showed that Cd treatment resulted in reduced expression levels of nuclear factor erythroid 2-related factor-2 (Nrf2), superoxide dismutase (SOD), catalase (CAT) and NAD(P)H: quinone oxidoreductase 1 (NQO1), and an increased expression level of malondialdehyde (MDA); the expression levels of Bcl-2 associated X (Bax) and caspase-3 increased, whereas that of B-cell lymphoma 2 (Bcl-2) decreased. Changes in m6A methylation-related enzymes were noted with Cd-induced damage to granulosa cells. The results of transcriptome and MeRIP sequencing revealed that the AKT pathway participated in Cd-induced damage in granulosa cells, and the MAX network transcriptional repressor (MNT) may be a potential target gene of fat mass and obesity-associated protein (FTO). FTO and YTH domain family member 2 (YTHDF2) regulated MNT expression through m6A modification. FTO overexpression alleviated Cd-induced apoptosis and oxidative stress through the activation of the AKT/Nrf2 pathway; this process could be reversed using siMNT. Overall, these findings associated m6A with Cd-induced damage to granulosa cells and provided insights into Cd-induced granulosa cell cytotoxicity from a new perspective centered on m6A modification.

Barriers and facilitators to implementing measurement-based care for depression in Shanghai, China: a situational analysis.

BACKGROUND: Measurement-based care (MBC) is an evidence-based practice for depression, but its use by clinicians remains low. Enhanced MBC (eMBC), which uses digital technologies, can help to facilitate the use of MBC by clinicians and patients. Understanding factors that act as barriers and drivers to the implementation of MBC and eMBC is important to support the design of implementation strategies, promoting uptake by clinicians and patients. OBJECTIVE: This situational analysis identifies barriers and facilitators to the implementation of standard and eMBC at mental health centers in Shanghai, China. METHODS: We used mixed methods to develop a comprehensive understanding of the factors influencing MBC and eMBC implementation in Shanghai. This study took place across three mental health centers in Shanghai. We used situational analysis tools to collect contextual information about the three centers, conducted surveys with n = 116 clinicians and n = 301 patients, conducted semi-structured interviews with n = 30 clinicians and six focus groups with a total of n = 19 patients. Surveys were analysed using descriptive statistics, and semi-structured interviews and focus groups were analysed using framework analysis. RESULTS: Several potential barriers and facilitators to MBC and eMBC implementation were identified. Infrastructure, cost, attitudes and beliefs, and perceptions about feasibility and efficacy emerged as both challenges and drivers to MBC and eMBC implementation in Shanghai. CONCLUSIONS: The results of this study will directly inform the design of an implementation strategy for MBC and eMBC in Shanghai, that will be tested via a randomized controlled trial. This study contributes to the emerging body of literature on MBC implementation and, to the best of our knowledge, is the first such study to take place in Asia. This study identifies several factors that are relevant to the equitable delivery of MBC, recognizing the need to explicitly address equity concerns in global mental health implementation research.

Brassinosteroids regulate outer ovule integument growth in part via the control of INNER NO OUTER by BRASSINOZOLE-RESISTANT family transcription factors.

Brassinosteroids (BRs) play important roles in regulating plant reproductive processes. BR signaling or BR biosynthesis null mutants do not produce seeds under natural conditions, but the molecular mechanism underlying this infertility is poorly understood. In this study, we report that outer integument growth and embryo sac development were impaired in the ovules of the Arabidopsis thaliana BR receptor null mutant bri1-116. Gene expression and RNA-seq analyses showed that the expression of INNER NO OUTER (INO), an essential regulator of outer integument growth, was significantly reduced in the bri1-116 mutant. Increased INO expression due to overexpression or increased transcriptional activity of BRASSINAZOLE-RESISTANT 1 (BZR1) in the mutant alleviated the outer integument growth defect in bri1-116 ovules, suggesting that BRs regulate outer integument growth partially via BZR1-mediated transcriptional regulation of INO. Meanwhile, INO expression in bzr-h, a null mutant for all BZR1 family genes, was barely detectable; and the outer integument of bzr-h ovules had much more severe growth defects than those of the bri1-116 mutant. Together, our findings establish a new role for BRs in regulating ovule development and suggest that BZR1 family transcription factors might regulate outer integument growth through both BRI1-dependent and BRI1-independent pathways.

The antagonistic regulation of abscisic acid-inhibited root growth by brassinosteroids is partially mediated via direct suppression of ABSCISIC ACID INSENSITIVE 5 expression by BRASSINAZOLE RESISTANT 1.

Brassinosteroids (BRs) and abscisic acid (ABA) are plant hormones that antagonistically regulate many aspects of plant growth and development; however, the mechanisms that regulate the crosstalk of these two hormones are still not well understood. BRs regulate plant growth and development by activating BRASSINAZOLE RESISTANT 1 (BZR1) family transcription factors. Here we show that the crosstalk between BRs and ABA signalling is partially mediated by BZR1 regulated gene expression. bzr1-1D is a dominant mutant with enhanced BR signalling; our results showed that bzr1-1D mutant is less sensitive to ABA-inhibited primary root growth. By RNA sequencing, a subset of BZR1 regulated ABA-responsive root genes were identified. Of these genes, the expression of a major ABA signalling component ABA INSENSITIVE 5 (ABI5) was found to be suppressed by BR and by BZR1. Additional evidences showed that BZR1 could bind strongly with several G-box cis-elements in the promoter of ABI5, suppress the expression of ABI5 and make plants less sensitive to ABA. Our study demonstrated that ABI5 is a direct target gene of BZR1, and modulating the expression of ABI5 by BZR1 plays important roles in regulating the crosstalk between the BR and ABA signalling pathways.

Restriction modification system analysis and development of in vivo methylation for the transformation of Clostridium cellulovorans.

Clostridium cellulovorans, a cellulolytic bacterium producing butyric and acetic acids as main fermentation products, is a promising host for biofuel production from cellulose. However, the transformation method of C. cellulovorans was not available, hindering its genetic engineering. To overcome this problem, its restriction modification (RM) systems were analyzed and a novel in vivo methylation was established for its successful transformation in the present study. Specifically, two RM systems, Cce743I and Cce743II, were determined. R. Cce743I has the same specificity as LlaJI, recognizing 5'-GACGC-3' and 5'-GCGTC-3', while M. Cce743I methylates the external cytosine in the strand (5'-GACG(m)C-3'). R. Cce743II, has the same specificity as LlaI, recognizing 5'-CCAGG-3' and 5'-CCTGG-3', while M. Cce743II methylates the external cytosine of both strands. An in vivo methylation system, expressing M. Cce743I and M. Cce743II from C. cellulovorans in Escherichia coli, was then established to protect plasmids used in electrotransformation. Transformants expressing an aldehyde/alcohol dehydrogenase (adhE2), which converted butyryl-CoA to n-butanol and acetyl-CoA to ethanol, were obtained. For the first time, an effective transformation method was developed for metabolic engineering of C. cellulovorans for biofuel production directly from cellulose.

Regulated inactivation of the spindle assembly checkpoint without functional mitotic spindles.

The spindle assembly checkpoint (SAC) arrests mitosis until bipolar attachment of spindle microtubules to all chromosomes is accomplished. However, when spindle formation is prevented and the SAC cannot be satisfied, mammalian cells can eventually overcome the mitotic arrest while the checkpoint is still activated. We find that Aspergillus nidulans cells, which are unable to satisfy the SAC, inactivate the checkpoint after a defined period of mitotic arrest. Such SAC inactivation allows normal nuclear reassembly and mitotic exit without DNA segregation. We demonstrate that the mechanisms, which govern such SAC inactivation, require protein synthesis and can occur independently of inactivation of the major mitotic regulator Cdk1/Cyclin B or mitotic exit. Moreover, in the continued absence of spindle function cells transit multiple cell cycles in which the SAC is reactivated each mitosis before again being inactivated. Such cyclic activation and inactivation of the SAC suggests that it is subject to cell-cycle regulation that is independent of bipolar spindle function.

Metabolic and process engineering of Clostridium cellulovorans for biofuel production from cellulose.

Production of cellulosic biofuels has drawn increasing attention. However, currently no microorganism can produce biofuels, particularly butanol, directly from cellulosic biomass efficiently. Here we engineered a cellulolytic bacterium, Clostridium cellulovorans, for n-butanol and ethanol production directly from cellulose by introducing an aldehyde/alcohol dehydrogenase (adhE2), which converts butyryl-CoA to n-butanol and acetyl-CoA to ethanol. The engineered strain was able to produce 1.42 g/L n-butanol and 1.60 g/L ethanol directly from cellulose. Moreover, the addition of methyl viologen as an artificial electron carrier shifted the metabolic flux from acid production to alcohol production, resulting in a high biofuel yield of 0.39 g/g from cellulose, comparable to ethanol yield from corn dextrose by yeast fermentation. This study is the first metabolic engineering of C. cellulovorans for n-butanol and ethanol production directly from cellulose with significant titers and yields, providing a promising consolidated bioprocessing (CBP) platform for biofuel production from cellulosic biomass.

Intramolecular cascade reaction sensing platform for rapid, specific and ultrasensitive detection of nitrite.

Nitrite is a carcinogenic substance in food. Excessive consumption of nitrite severely endangers human health. However, rapid and accurate quantification of nitrite by a simple tool is still very challenging. In this work, we designed a practical sensing platform based on 8-(o-phenylenediamine)-boron dipyrromethene (BDP-OPD) to determine nitrite in food. BDP-OPD can take a specific diazotization-cyclization cascade reaction with nitrite to form boron dipyrromethene (BODIPY), giving rise to a remarkable chromogenic reaction along with high contrast fluorescence turn-on response towards nitrite. BDP-OPD has high sensitivity, rapid response, and good selectivity. Furthermore, a portable smartphone-based fluorescence device integrated with a self-programmed Python program was fabricated, which has been successfully used to determine nitrite in food with the advantages of rapid response, low cost, ease of operation, portability, and satisfactory recoveries (92-112%). The good sensing performance rendered BDP-OPD a promising fluorescence platform for on-site visual detection of nitrite.

Comparative Anatomical Analysis of Bark Structure in 10 Quercus Species.

Detailed anatomical features of bark are used and interpreted in plant taxonomy, phylogenetics, and other areas of plant science. However, the delicate nature of bark cells, combined with the difficulty of obtaining high-quality sections and reliable data, limits the potential for utilizing and processing bark. In this study, the anatomical structure of the bark of 10 Quercus species growing in Yunnan Province, China, was characterized in detail. The results indicate that the anatomical features of the barks of 10 Quercus spp. show a certain degree of consistency. Specifically, sieve tubes are distributed in solitary elements or in small groups, mostly as compound sieve plates containing 2-8 sieve areas, suggesting that Quercus spp. may occupy a conservative evolutionary position. Additionally, for the first time, this study reports the presence of simple sieve plates in the sieve tube elements of Quercus phloem. Each sieve tube element has a companion cell on one side. The companion cell strands contain 2-7 cells. Axial parenchyma is diffuse, with parenchyma strands typically consisting of 4-7 cells; druses are present within chambered crystalliferous cells. Phloem rays are of two distinct sizes and often exhibit dilatation and sclerification, and the ray composition consists of procumbent cells. Sclerenchyma is composed of fibers and sclereids, both of which contain prismatic crystals. Most of the fibers are gelatinous fibers, which are distributed in discontinuous tangential bands of about five cells in width. Sclereids appear in clusters. The presence of sclerenchyma provides mechanical support to the bark, reducing the collapse of the phloem. Periderm usually consists of around 10-30 layers of phellem, and Quercus acutissima and Q. variabilis can reach dozens or hundreds layers. The phelloderm typically consists of from two to five layers, with Q. variabilis having up to ten or more layers. The filling tissue of lenticels in all Quercus species is nonstratified (homogeneous) and largely nonsuberized. Overall, this study enriches our comprehension of Quercus bark anatomy, elucidating evolutionary patterns, functional adaptations, and ecological ramifications within this significant botanical genus.

A tuned triboelectric nanogenerator using a magnetic liquid for low-frequency vibration energy harvesting.

Wireless sensor networks have developed quickly in recent years, and the use of self-powered technology to replace traditional external power sources to power sensor nodes has become an urgent problem that needs to be solved. As an entirely novel type of self-powered technology, the triboelectric nanogenerator (TENG) has attracted widespread attention, but the inability to achieve adaptive adjustment based on the vibration environment has restricted the development of TENGs. Here, a magnetic liquid triboelectric nanogenerator (ML-TENG) is designed to harvest vibration energy to power sensing nodes, and ML-TENG tuning is achieved using a magnetic liquid to adapt to different vibration environments. The electrical performance of the ML-TENG was investigated by theoretical, experimental, and numerical research. According to the results, the developed ML-TENG responds well to low-frequency vibration, and the instantaneous power is up to 5.40 nW. The tuning function is achieved by adjusting the magnetic field, and the natural frequency can be adjusted between 6.6 Hz and 7.6 Hz. The strong linear connection between the output voltage of the ML-TENG and the external environment's vibration amplitude promotes the monitoring of the vibration environment and lays the groundwork for the creation of wireless sensor networks.

Quantitative phosphoproteomics explain cryopreservation-induced reductions in ram sperm motility.

Sperm cryopreservation decreases motility, probably due to changes in protein phosphorylation. Our objective was to use quantitative phosphoproteomics for systematic comparative analyses of fresh versus frozen-thawed sperm to identify factors causing cryo-injury. Ejaculates were collected (artificial vagina) from six Dorper rams, pooled, extended, and frozen over liquid nitrogen. Overall, 915, 3382, and 6875 phosphorylated proteins, phosphorylated peptides, and phosphorylation sites, respectively, were identified. At least two modified sites were present in 57.94% of the 6875 phosphosites identified, of which AKAP4 protein contained up to 331 modified sites. There were 732 phosphorylated peptides significantly up-regulated and 909 significantly down-regulated in frozen-thawed versus fresh sperm. Moreover, the conserved motif [RxxS] was significantly down-regulated in frozen-thawed sperm. Phosphorylation of sperm-specific proteins, e.g., AKAP3/4, CABYR, FSIP2, GSK3A/B, GPI, and ODF1/2 make them potential biomarkers to assess the quality of frozen-thawed ram sperm. Furthermore, these differentially phosphorylated proteins and modification sites were implicated in cryopreservation-induced changes in sperm energy production, fiber sheath composition, and various biological processes. We concluded that abnormal protein phosphorylation modifications are key regulators of reduced sperm motility. These novel findings implicated specific protein phosphorylation modifications in sperm cryo-injury. SIGNIFICANCE: This study used phosphorylated TMT quantitative proteomics to explore regulation of epigenetic modifications in frozen-thawed ram sperm. This experiment demonstrated that ram sperm freezing affects phosphorylation site modifications of proteins, especially those related to functions such as sperm motility and energy production. Furthermore, it is important to link functions of phosphorylated proteins with changes in sperm quality after freezing and thawing, and to clarify intrinsic reasons for sperm quality changes, which is of great importance for elucidating mechanisms of sperm freezing damage. Based on these protein markers and combined with cryoprotectant design theory, it provides a theoretical basis and data reference to study sperm cryoprotectants.

A portable europium complex-loaded fluorescent test paper combined with smartphone analysis for the on-site and visual detection of mancozeb in food samples.

The on-site detection of mancozeb in food samples holds immense value for food safety. A red-fluorescent europium complex (Eu-PYDC-Phen) has been prepared and employed as a fluorescence probe for mancozeb detection. The optimized probe suspension exhibits excellent detection performances, including a wide linear range (0-0.24 mM), low detection limit (65 nM), rapid response (2 mins) and high selectivity. Moreover, a portable detection platform was carefully designed, integrating the Eu-PYDC-Phen-based fluorescent test strips with smartphone color recognition software. This innovative platform enables visual and on-site detection of mancozeb in tomato, apple, and lettuce, achieving satisfactory recovery rates (90.34 to 106.50%). Furthermore, the integration of machine learning techniques based on hierarchical clustering algorithm has the potential to further improve the prediction and decision-making efficiency in mancozeb detection. This work provides an economical, convenient, and reliable strategy for on-site detection of pesticide in agricultural products, thereby making a meaningful contribution to food safety.

A smartphone-integrated test paper sensing platform for visual and intelligent detection of nitrofurantoin in honey samples.

The development of a rapid and convenient detection method for nitrofurantoin (NFT) residual is of great significance for food safety. Herein, a new fluorescent probe (Eu-TDCA-Phen) was developed for the visual and sensitive assay of NFT through the fluorescence quenching effect of inner filter effect (IFE) and photo-induced electron transfer (PET). The probe suspension demonstrates a wide linear range (0-0.16 mM), low detection limit (90 nM), high sensitivity, and rapid response time (2 min) in the "turn-off" process. To quantify the visual detection process, a smartphone-assisted test paper sensing platform was established and was applied for NFT determination in real honey samples, achieving satisfactory recovery rate ranges from 98.04 % to 105.04 %. Furthermore, a logic gate device was integrated with the sensing platform to streamline the visual detection process. The sensing platform offers several merits, including simpleness, quantification, portability and cost-effectiveness, making it highly suitable for real-time and on-site detection of antibiotics in food samples.

Recent selection and introgression facilitated high-altitude adaptation in cattle.

During the past 3000 years, cattle on the Qinghai-Xizang Plateau have developed adaptive phenotypes under the selective pressure of hypoxia, ultraviolet (UV) radiation, and extreme cold. The genetic mechanism underlying this rapid adaptation is not yet well understood. Here, we present whole-genome resequencing data for 258 cattle from 32 cattle breeds/populations, including 89 Tibetan cattle representing eight populations distributed at altitudes ranging from 3400 m to 4300 m. Our genomic analysis revealed that Tibetan cattle exhibited a continuous phylogeographic cline from the East Asian taurine to the South Asian indicine ancestries. We found that recently selected genes in Tibetan cattle were related to body size (HMGA2 and NCAPG) and energy expenditure (DUOXA2). We identified signals of sympatric introgression from yak into Tibetan cattle at different altitudes, covering 0.64%-3.26% of their genomes, which included introgressed genes responsible for hypoxia response (EGLN1), cold adaptation (LRP11), DNA damage repair (LATS1), and UV radiation resistance (GNPAT). We observed that introgressed yak alleles were associated with noncoding variants, including those in present EGLN1. In Tibetan cattle, three yak introgressed SNPs in the EGLN1 promoter region reduced the expression of EGLN1, suggesting that these genomic variants enhance hypoxia tolerance. Taken together, our results indicated complex adaptation processes in Tibetan cattle, where recently selected genes and introgressed yak alleles jointly facilitated rapid adaptation to high-altitude environments.

Macrophage Polarization and the Regulation of Bone Immunity in Bone Homeostasis.

Bone homeostasis is a dynamic equilibrium state of bone formation and absorption, ensuring skeletal development and repair. Bone immunity encompasses all aspects of the intersection between the skeletal and immune systems, including various signaling pathways, cytokines, and the crosstalk between immune cells and bone cells under both homeostatic and pathological conditions. Therefore, as key cell types in bone immunity, macrophages can polarize into classical pro-inflammatory M1 macrophages and alternative anti-inflammatory M2 macrophages under the influence of the body environment, participating in the regulation of bone metabolism and playing various roles in bone homeostasis. M1 macrophages can not only act as precursors of osteoclasts (OCs), differentiate into mature OCs, but also secrete pro-inflammatory cytokines to promote bone resorption; while M2 macrophages secrete osteogenic factors, stimulating the differentiation and mineralization of osteoblast precursors and mesenchymal stem cells (MSCs), and subsequently increase bone formation. Once the polarization of macrophages is imbalanced, the resulting immune dysregulation will cause inflammatory stimulation, and release a large amount of inflammatory factors affecting bone metabolism, leading to pathological conditions such as osteoporosis (OP), rheumatoid arthritis (RA), and steroid-induced femoral head necrosis (SANFH). In this review, we introduce the signaling pathways and related factors of macrophage polarization, as well as their relationships with immune factors, OB, OC, and MSC. We also discuss the roles of macrophage polarization and bone immunity in various diseases of bone homeostasis imbalance, as well as the factors regulating them, which may help to develop new methods for treating bone metabolic disorders.

Hybrid multi-strategy chaos somersault foraging chimp optimization algorithm research.

To address the problems of slow convergence speed and low accuracy of the chimp optimization algorithm (ChOA), and to prevent falling into the local optimum, a chaos somersault foraging ChOA (CSFChOA) is proposed. First, the cat chaotic sequence is introduced to generate the initial solutions, and then opposition-based learning is used to select better solutions to form the initial population, which can ensure the diversity of the algorithm at the beginning and improve the convergence speed and optimum searching accuracy. Considering that the algorithm is likely to fall into local optimum in the final stage, by taking the optimal solution as the pivot, chimps with better adaptation at the mirror image position replace chimps from the original population using the somersault foraging strategy, which can increase the population diversity and expand the search scope. The optimization search tests were performed on 23 standard test functions and CEC2019 test functions, and the Wilcoxon rank sum test was used for statistical analysis. The CSFChOA was compared with the ChOA and other improved intelligent optimization algorithms. The experimental results show that the CSFChOA outperforms most of the other algorithms in terms of mean and standard deviation, which indicates that the CSFChOA performs well in terms of the convergence accuracy, convergence speed and robustness of global optimization in both low-dimensional and high-dimensional experiments. Finally, through the test and analysis comparison of two complex engineering design problems, the CSFChOA was shown to outperform other algorithms in terms of optimal cost. For the design of the speed reducer, the performance of the CSFChOA is 100% better than other algorithms in terms of optimal cost; and, for the design of a three-bar truss, the performance of the CSFChOA is 6.77% better than other algorithms in terms of optimal cost, which verifies the feasibility, applicability and superiority of the CSFChOA in practical engineering problems.