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Abstract Prostate cancer (PCa) is one of the most common and prevalent cancers in men worldwide. The majority of PCa-related deaths result from metastasis rather than primary tumors. Several studies have focused on the relationship between male-specific genes encoded on the Y chromosome and PCa metastasis; however, the relationship between the male specific protein encoded on the Y chromosome and tumor suppression has not been fully clarified. Here, we report a male specific protein of this type, the histone H3 lysine 4 (H3K4) demethylase JARID1D, which has the ability to inhibit the gene expression program related to cell invasion, and can thus form a phenotype that inhibits the invasion of PCa cells. However, JARID1D exhibits low expression level in advanced PCa, and which is related to rapid invasion and metastasis in patients with PCa. Curcumin, as a multi-target drug, can enhance the expression and demethylation activity of JARID1D, affect the androgen receptor (AR) and epithelial-mesenchymal transition (EMT) signaling cascade, and inhibit the metastatic potential of castration resistant cancer (CRPC). These findings suggest that using curcumin to increase the expression and demethylation activity of JARID1D may be a feasible strategy to inhibit PCa metastasis by regulating EMT and AR.

The effect of initial grain size prior to cold rolling on the microstructure, texture evolution, and magnetic properties of Fe-3.5 wt% Si non-oriented electrical steel (NOES) was investigated through the introduction of normalization. There were massive intragranular shear bands in {111} and {111} deformed grains in the cold-rolled sheet with large initial grain size, providing nucleation sites for new recrystallized grains with Goss ({110}), λ-fiber, γ-fiber, and {113} components. Subsequent annealing resulted in weaker γ-fiber ({111}−{111}), stronger α*-fiber concentrated at {113}, along with Goss and λ-fiber ({100}−{100}) textures. In addition, appropriate final annealing temperature effectively reduced iron loss. The simultaneous optimization of texture and grain size by normalization and annealing treatments led to improved magnetic properties, with the superior magnetic induction (B50 = 1.719) T, and the lowest core loss (P15/50 = 2.69 W/kg, P10/400 = 16.337 W/kg).

The large area overhanging of thick and hard roof is one of the critical reasons for inducing coal burst. Because of the shortcomings of deep borehole blasting and conventional hydraulic fracturing for the overhanging roof, the axial roof cutting technology of abrasive jet was developed. This technology achieves the best pressure relief by implementing prefabricated axial fractures and directional hydraulic fracturing in the roadway roof borehole to create an artificial fracture network in the roadway direction and tendency direction that is most conducive to roof collapse. The field application shows that the electromagnetic wave absorption ability of the stratum was enhanced, and the apparent resistivity was increased after the axial cutting roof technology of abrasive jet was implemented. During the mining operation of working face, the stress condition of the support was improved, and the release of micro-seismic energy was more stable, effectively reducing the risk of coal burst. On the basis of site observation, the mechanism of coal burst prevention by axial roof cutting of abrasive jet was revealed, that is, the plate-like structure fixed on both sides near the working face end is damaged by axial roof cutting, reducing the basic static load Ej, which is converted from the bending elastic energy of roof into the compression elastic energy of roadway surrounding rock, and reducing the strong additional dynamic load Ed, which is generated by the sudden fracture of roof, so that the roadway surrounding rock does not have the loading conditions for starting coal burst.

Abstract Adipose tissue development begins in the fetal period, and continues to expand after birth. Dysregulation of adipose tissue during weaning may predispose individuals to lifelong metabolic disorders. However, the developmental remodeling of adipose tissue during weaning remains largely unexplored. Here we comprehensively compare the changes in mouse subcutaneous white adipose tissue from 7 days after birth to 7 days after weaning using single-cell RNA sequencing along with other molecular and histologic assays. We characterize the developmental trajectory of preadipocytes and indicate the commitment of preadipocytes with beige potential during weaning. Meanwhile, we find immune cells unique to weaning period, whose expression of extracellular matrix proteins implies potential regulation on preadipocyte. Finally, the strongest cell-cell interaction during weaning determined by the TGFβ ligand-receptor pairs is between preadipocytes and endotheliocytes. Our results provide a detailed and unbiased cellular landscape and offer insights into the potential regulation of adipose tissue remodeling during weaning.

With the construction of the Three Gorges Reservoir dam, frequent reservoir landslide events have been recorded. In recent years, multi-row stabilizing piles (MRSPs) have been used to stabilize massive reservoir landslides in China. In this study, two centrifuge model tests were carried out to study the unreinforced and MRSP-reinforced slopes subjected to reservoir water level (RWL) operation, using the Taping landslide as a prototype. The results indicate that the RWL rising can provide lateral support within the submerged zone and then produce the inward seepage force, eventually strengthening the slope stability. However, a rapid RWL drawdown may induce outward seepage forces and a sudden debuttressing effect, consequently reducing the effective soil normal stress and triggering partial pre-failure within the RWL fluctuation zone. Furthermore, partial deformation and subsequent soil structure damage generate excess pore water pressures, ultimately leading to the overall failure of the reservoir landslide. This study also reveals that a rapid increase in the downslope driving force due to RWL drawdown significantly intensifies the lateral earth pressures exerted on the MRSPs. Conversely, the MRSPs possess a considerable reinforcement effect on the reservoir landslide, transforming the overall failure into a partial deformation and failure situated above and in front of the MRSPs. The mechanical transfer behavior observed in the MRSPs demonstrates a progressive alteration in relation to RWL fluctuations. As the RWL rises, the mechanical states among MRSPs exhibit a growing imbalance. The shear force transfer factor (i.e. the ratio of shear forces on pile of the nth row to that of the first row) increases significantly with the RWL drawdown. This indicates that the mechanical states among MRSPs tend toward an enhanced equilibrium. The insights gained from this study contribute to a more comprehensive understanding of the failure mechanisms of reservoir landslides and the mechanical behavior of MRSPs in reservoir banks.

Objects: To evaluate the association of direct oral anticoagulants (DOACs) and warfarin with dementia incidence in atrial fibrillation (AF) patients. Methods: Relevant studies were retrieved in databases including Embase, PubMed, Cochrane, Web of Knowledge, and ClinicalTrials.gov. Meta-analysis was then conducted using Stata 12.0 software. Results: A total of 9 studies involving 447,644 AF patients were included. The results indicated that AF patients treated with DOACs had a lower incidence of dementia compared to those treated with warfarin (RR: 0.692, 95 % CI: 0.603–0.793, P = 0.000), This trend was observed in both age groups,

Elucidating the effects of long-term cultivation on pore structure and infiltration characteristics is essential for understanding soil degradation mechanism and improving cropland sustainability. In this study, we evaluated a number of indicators regarding soil properties, pore structure, and water infiltration during long-term cultivation and the relationship of basic properties and pore structure with soil infiltration in northeast Mollisol region of China. The studied cropland involved four cultivation durations (20, 40, 60, and 100 years) and one forest (FR) as the control. X-ray computed tomography (CT) and mini disk infiltrometer were applied to assess the effects of long-term cultivation on soil pore structure and infiltration characteristics at soil depths of 0–100 cm. The pore properties including soil porosity (TP), pore number (PN), pore size distribution, mean shape factor (MSF), fractal dimension (FA), anisotropy (DA), and Euler number (EN), and infiltration properties including mean (IR), initial (IIR), stable infiltration rate (SIR), and saturated hydraulic conductivity (Ks) were planned to be measured in this study. The results showed that soil organic carbon (SOC) in cropland was significantly lower than that in FR, while bulk density (BD) and mean weight diameter (MWD) exhibited an opposite trend. Long-term cultivation altered the soil pore size and shape distribution, and decreased the macroporosity (>500 μm) and elongated porosity, which suggested that long-term cultivation results in a simpler pore network. FR took a longer time to reach a stable state in infiltration curve over time, while cropland had lower IR, IIR, SIR and Ks, indicating negative effects of cultivation on water infiltration. > 500 μm porosity and elongated porosity were positively correlated with infiltration characteristics (P

With the continuous increase of coal mining depth, the occurrence and prevention of deep rockburst in China have become normalized. In order to improve the effectiveness of deep rockburst prevention and control technology, starting from the technical difficulties of deep rockburst prevention and control in on-site engineering, combined with practical data statistics of disaster prevention and control engineering, this study demonstrates that the deep rockburst in China is due to its high geological stress and large range of human mining disturbance. The stress recovery of surrounding rock is fast after rock stress unloading during the disaster prevention and control process. The low effectiveness of rockburst prevention and control can be attributed to the new requirements of “three highs and one low” prevention and control technology in deep mining compared to that in shallow mining, including high-strength large-sized drilling to relieve pressure, in order to solve the collapse prone problem of thick and hard coal seams; small spacing high-density drilling to solve the problem of disconnected pressure relief range in drilling; multiple rounds of repeated high-frequency construction to solve the problem of rapid stress recovery after unloading pressure in deep coal seams; and the mining face is advancing at a low speed to solve the problem of high mining disturbance intensity. In response to the new requirements of “three highs and one low” prevention and control mode for deep rockburst, in order to further improve the safety and reliability of rockburst prevention and control, and based on the limitations of optimizing development and mining deployment for conventional source rockburst prevention and control, this paper proposes the technology of actively regulating the structure and load of overlying rock layers in the deep rockburst prevention and control areas, and presents some further scientific problems that need to be solved. Against the background of several typical rockburst accidents in recent years with the problem of “missed targets” in the prevention and control plans, a local targeted prevention and control technology for deep rockburst mining space has been developed, and the scientific challenges that need to be solved in the future have been pointed out. Against the background of the difficulty in evaluating safety issues after the implementation of coal mine rockburst prevention and control measures, a deep rockburst prevention and control unloading standard evaluation technology is proposed, and the scientific difficulties that need to be solved in the future are pointed out. The coal industry vigorously promotes intelligent mining, but the disaster control still relies on manual labor and personnel to operate in a high-risk environment. This paper also explores the emerging research direction and scientific challenges of intelligent mining and intelligent prevention and control of deep rockburst. Finally, it is objectively pointed out that the prevention and control of rockburst is not purely a theoretical and technical issue, and the human understanding of technical issues is also one of the important reasons for rockburst accidents. Combining with the on-site engineering practice, this paper discusses the concept and mechanism of rockburst, whether rockburst can be predicted, whether rockburst can be prevented and controlled, and how to deal with rockburst mines and other industry focused technical issues. It is pointed out that the problem of rockburst engineering is a struggle between humans and nature, which requires practitioners to objectively understand, objectively accept, and conduct in-depth research. The current achievement is of significance.

Abstract Cation exchanger (CAX) genes play an important role in plant growth/development and response to biotic and abiotic stresses. Here, we tried to obtain important information on the functionalities and phenotypic effects of CAX gene family by systematic analyses of their expression patterns, genetic diversity (gene CDS haplotypes, structural variations, gene presence/absence variations) in 3010 rice genomes and nine parents of 496 Huanghuazhan introgression lines, the frequency shifts of the predominant gcHaps at these loci to artificial selection during modern breeding, and their association with tolerances to several abiotic stresses. Significant amounts of variation also exist in the cis-regulatory elements (CREs) of the OsCAX gene promoters in 50 high-quality rice genomes. The functional differentiation of OsCAX gene family were reflected primarily by their tissue and development specific expression patterns and in varied responses to different treatments, by unique sets of CREs in their promoters and their associations with specific agronomic traits/abiotic stress tolerances. Our results indicated that OsCAX1a and OsCAX2 as general signal transporters were in many processes of rice growth/development and responses to diverse environments, but they might be of less value in rice improvement. OsCAX1b, OsCAX1c, OsCAX3 and OsCAX4 was expected to be of potential value in rice improvement because of their associations with specific traits, responsiveness to specific abiotic stresses or phytohormones, and relatively high gcHap and CRE diversity. Our strategy was demonstrated to be highly efficient to obtain important genetic information on genes/alleles of specific gene family and can be used to systematically characterize the other rice gene families.

In this study, a dynamic headspace (DHS) combined with thermal desorption/gas chromatography-mass spectrometry (TD/GC-MS) method was established to analyze the volatile composition of baked green tea. Extraction parameters including tea amount, trapping temperature, incubation temperature, total purge volume, purge rate, and drying rate were optimized. Furthermore, the key odorants of baked green tea made from different tea cultivars were identified by gas chromatography-olfactometry-mass spectrometry (GC-O-MS). The results indicated that the optimal extraction conditions were as follows: tea amount of 200 mg, trapping temperature of 70 ℃, incubation temperature of 70 ℃, total purge volume of 350 mL, purge rate of 10 mL/min, and drying rate of 10 mL/min. A total of 74 volatile components were identified in green tea made from three representative varieties. Multivariate statistical analysis showed that the aroma compounds of the three green teas varied greatly, and 18 key differential volatile aroma components were identified. The contents of isopropylidesneacetone and linalool in LongJing 43 (LJ 43) baked green tea were the highest among these three teas. Fuding Dabaicha (FDDB) baked green tea contained the highest levels of 6-methyl-5-heptene-2-one, octanal, cyclohexanone, acetophenone, copaene and epicubenol. A total of 28 odorants were identified by GC-O-MS analysis. The odorants were mainly responsible for odor attributes such as green, refreshing, floral, fruity, herbal, woody and sweet aromas. The total aroma intensity of floral and fruity attributes was the highest, followed by the green and refreshing attributes. Taken collectively, linalool, calamenene, δ-cadinene, 6-methyl-5-heptene-2-one and octanal were the key differential odorants among the three green teas. Linalool contributed significantly to LJ 43 baked green tea, and the other four odorants contributed significantly to the formation of the aroma quality of FDDB baked green tea.

Abstract Background Psoriasis is a chronic inflammatory genetic disease, mainly manifesting in the skin. Conventional therapies, such as glucocorticosteroids and corticosteroids, have adverse effects that limit drug use. Hence, it is imperative to identify a new therapeutic strategy that exhibits a favorable safety profile. Shi-Bi-Man (SBM) is a safe herbal supplement sourced from various natural plants, including ginseng, angelica sinensis, polygonum multiflorum, and aloe vera. Purpose We aimed to find a potential treatment for psoriasis and investigate the underlying mechanism through which SBM alleviates psoriatic-like skin inflammation in mice. Methods We investigated the effects of supplementing with SBM through intragastric administration or smear administration in a murine model of imiquimod-induced psoriasis. The changes in body weight and Psoriasis Area and Severity Index (PASI) score were recorded throughout the entire process. Additionally, we used hematoxylin–eosin staining to observe the skin structure and performed single-cell RNA sequencing to explore the underlying mechanism of SBM in influencing the psoriasis-like phenotype. Immunofluorescence was conducted to verify our findings. Furthermore, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to investigate the impact of Tetrahydroxy stilbene glycoside (TSG) on the expression levels of IL23 in HaCaT cells. Results SBM remarkably alleviated the psoriasis-like phenotype by inhibiting IL-23/Th17 cell axis. Single-cell RNA sequencing analysis revealed a decrease in the expression of Il17 and Il23 in keratinocytes and T cells, concomitant with a reduction in the proportion of Th17 cells. Meanwhile, the activation of endothelial cells was inhibited, accompanied by a decrease in the expression of Cxcl16. In vitro, the addition of TSG to HaCaT cells resulted in significant suppression of IL23 expression stimulated by tumor necrosis factor-alpha (TNF-α).

Objective: The prognosis of malignant tumors with peritoneal metastases and cancerous ascites has generally been poor, with limited treatment options. The PRaG regimen, which comprised of hypofractionated radiotherapy, programmed cell death-1 (PD-1) inhibitor, and granulocyte-macrophage colony-stimulating factor (GM-CSF), showed a survival advantage in patients with advanced solid tumors who failed at least the first line of standard systemic treatment. Intraperitoneal infusion of PD-1 inhibitors may be a novel therapeutic strategy for managing malignant ascites. Integrating the PRaG regimen with intraperitoneal perfusion of a PD-1 inhibitor might control malignant ascites and provide further survival benefits in these patients. This proposed study aims to investigate the safety and efficacy of intraperitoneal infusion of serplulimab in combination with the PRaG regimen in patients with simultaneous advanced solid tumors and cancerous ascites who fail at least the first-line treatment. Methods: This proposed study is a prospective, single-arm, open-label, multicenter clinical trial. All eligible patients will receive 2 cycles of intensive treatment, a combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor. The patients who are beneficially treated with intensive treatment will receive consolidation treatment every 2 weeks until ascites disappear, disease progression occurs, intolerable toxicity occurs, or for up to 1 year. Phase I of this study will be conducted using a modified 3 + 3 design. The dose of intraperitoneal infusion of PD-1 inhibitor for phase II will be determined according to dose-limiting toxicity evaluation in the phase I study. Conclusion: This prospective, open-label, multicenter study will potentially lead to intraperitoneal perfusion of a PD-1 inhibitor being a new strategy for malignant ascites patients and provide a meaningful efficacy and safety of the combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor for these patients.

Abstract In this study, a novel wide‐bandgap small molecule guest material, ITOA, designed and synthesized for fabricating efficient ternary organic solar cells (OSCs) ITOA complements the absorbance of the PM6:Y6 binary system, exhibiting strong crystallinity and modest miscibility. ITOA optimizes the morphology by promoting intensive molecular packing, reducing domain size, and establishing a preferred vertical phase distribution. These features contribute to improved and well‐balanced charge transport, suppressed carrier recombination, and efficient exciton dissociation. Consequently, a significantly enhanced efficiency of 18.62% for the ternary device is achieved, accompanied by increased short‐circuit current density (JSC), fill factor (FF), and open‐circuit voltage (VOC). Building on this success, replacing Y6 with BTP‐eC9 leads to an outstanding PCE of 19.33% for the ternary OSCs. Notably, the introduction of ITOA expedites the formation of the optimized morphology, resulting in an impressive PCE of 18.04% for the ternary device without any postprocessing. Moreover, the ternary device exhibits enhanced operational stability under maximum power point (MPP) tracking. This comprehensive study demonstrates that a rationally designed guest molecule can optimize morphology, reduce energy loss, and streamline the fabrication process, essential for achieving high efficiency and stability in OSCs, paving the way for practical commercial applications.

Abstract Aqueous zinc‐ion batteries (ZIBs) have attracted extensive interest for the next‐generation batteries, which, however, are facing great challenges due to the poor reversibility of zinc (Zn) anodes and side reactions of water decomposition. Herein, we demonstrated a strategy that the solvation sheath of Zn ions could be facilely regulated by supramolecular coordination chemistry by adding small amounts of cyclodextrins (CDs) and, hence, inhibited the side reactions and side products, widened the electrochemical window, facilitated the homogenous deposition of Zn ions, refined the Zn grains, and enhanced the stability of Zn anodes. Importantly, we demonstrated that compared with α‐ and β‐CD, the γ‐CD showed the best regulation effect of the solvation sheath of Zn ions either at the same molar ratio or at the same mass concentration, which could be ascribed to their difference in supramolecular coordination chemistry and the strongest interaction of γ‐CD with Zn ions. As a result, with γ‐CD, the Zn//Zn symmetric cells showed ultrahigh stability with a cycling lifespan of over 2400 h at a current density of 1 mA/cm2. These results highlight the regulation of solvation sheath by supramolecular coordination chemistry for highly stable Zn anodes and pave a new way to realize high‐performance ZIBs.

Reliable material parameters, correct boundary condition settings, and a reasonably simplified numerical model are key to obtain reliable and reasonable analysis results. A new finite element analysis model for the HgCdTe infrared focal plane array detector is presented, which includes the core column. The thermal stress and strain of the new model and current model are analyzed, and their distribution laws are obtained. The results are compared, and the reasons are analyzed, which can provide some references for the simulation of infrared detector package structure.

Potential geohazards triggered by the rock mass deterioration (RMD) of the hydro-fluctuation belt (HFB) in the Three Gorges Reservoir area (TGRA) severely threaten the lives and property of people, it is necessary and urgent to timely identify this kind of potential geohazard. Aiming at this issue, several typical evolution modes of potential RMD-induced geohazards were generalized, and an unmanned aerial vehicle (UAV) photographic method integrating the orthophotography, three-dimensional multi-angle oblique photography and high-precision digital elevation model (DEM) was proposed to early recognize the newly formed potential RMD-induced geohazards. By resolving the problem of poor precision in the orthophotographic images of high steep bank slopes, the proposed method improved the recognition reliability of potential reservoir geohazards in the HFBs. Taking the bank slopes from Zigui County to Badong County as the study area, 116 new potential RMD-induced geohazard sites were identified by the presented approach, including 64 and 52 sites on the left and right bank, respectively. Through field verifications, 17 and 19 sites on the left and right bank were found to be consistent with existing hazards, indicating the effectiveness of the proposed approach in avoiding the false and missing recognitions of potential RMD-induced reservoir geohazards at current levels of knowledge and technology. The study can provide a valuable reference for the early identification of RMD-induced geohazards in reservoir areas.

Introduction The PRaG regimen, which consists of hypofractionated radiotherapy combined with a programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitor and granulocyte-macrophage colony stimulating factor (GM-CSF), has been demonstrated to have a survival benefit in patients with advanced solid tumours who have failed at least two lines of treatment. Nonetheless, lymphopenia poses an impediment to the enduring efficacy of PD-1/PD-L1 inhibitor therapy. Adequate lymphocyte reserves are essential for the efficacy of immunotherapy. Coupling the PRaG regimen with immunomodulatory agents that augment the number and functionality of lymphocytes may yield further survival benefits in this cohort of patients.Objective The aim of this study is to investigate the effectiveness and safety of a meticulously thymalfasin-controlled PRaG regimen in patients with advanced and chemotherapy-resistant solid tumours.Methods and analysis The study has a prospective, single-arm, open-label, multicentre design and aims to recruit up to 60 patients with histologically confirmed advanced solid tumours that have relapsed or metastasised. All eligible patients will receive a minimum of two cycles of the PRaG regimen comprising thymalfasin followed by maintenance treatment with a PD-1/PD-L1 inhibitor and thymalfasin for 1 year or until disease progression. Patients will be monitored according to the predetermined protocol for a year or until disease progression after initiation of radiotherapy.Ethics and dissemination The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University, on 25 November 2022 (JD-LK-2022-151-01) and all other participating hospitals. Findings will be disseminated through national and international conferences. We also plan to publish our findings in high-impact peer-reviewed journal.Trial registration number NCT05790447.

ObjectivesRe-epithelialization is an important physiological process for repairing skin barrier function during wound healing. It is primarily mediated by coordinated migration, proliferation, and differentiation of keratinocytes. Long noncoding RNAs (lncRNAs) are essential components of the noncoding genome and participate in various biological processes; however, their expression profiles and function in re-epithelialization during wound healing have not been established.MethodsWe investigated the distribution of lncRNAs during wound re-epithelialization by comparing the genomic profiles of uninjured skin and acute wound (AW) from healthy donors. We performed functional screening of differentially expressed lncRNAs to identify the important lncRNAs for re-epithelialization.ResultsThe expression of multiple lncRNAs is changed during human wound re-epithelialization process. We identified VIM-AS1, SMAD5-AS1, and LINC02581 as critical regulators involved in keratinocyte migration, proliferation, and differentiation, respectively.ConclusionLncRNAs play crucial regulatory roles in wound re-epithelialization. We established lncRNA expression profile in human acute wounds compared with intact skin, offering valuable insights into the physiological mechanisms underlying wound healing and potential therapeutic targets.

The resurgence of passenger flows after the pandemic poses a significant challenge to the safe operation of rail transit. Therefore, adopting the waiting hall of an ultralarge railway station hub as an example, thermal radiation and evacuation simulations were conducted by the Fire Dynamics Simulator and Pathfinder, respectively. Island-style shops, known for their high crowd density and fire load, were defined as fire sources, and the effectiveness of a 6 m wide fire isolation zone was validated via the adoption of the dual-validation model. By comparing the relationships between the total evacuation population after passenger flow recovery and various evacuation parameters, it was shown that passengers were not evenly distributed among the exits in the waiting hall during an emergency, leading to uneven utilization. Furthermore, to gain a comprehensive understanding of the evacuation process under simulated fire conditions, an evacuation simulation involving 10,000 evacuees over a duration of 324.8 s was conducted. This study provides a theoretical basis for optimizing fire emergency evacuation plans for ultralarge railway station hubs.

Abstract Prunella vulgaris L. (P. vulgaris) has long been considered to have antipyretic, analgesic and anti-inflammatory effects, lowering blood lipids and pressure. Many studies show that in addition to the traditional telomere attrition, DNA damage and epigenetic changes, immunosenescence is also a new possibility to explore the mechanism of ageing. Therefore, this herb may have potential anti-ageing effects. Typically, there are a series of markers that identify senescent cells, such as superoxide dismutase (SOD)2, an inhibitor of CDK4 (p16INK4A), tumor necrosis factor (TNF)-α, immune cells number, proliferation, and nuclear abnormalities. These changes rarely present in young tissues, while greatly increasing in response to ageing. Firstly, the ageing model of the Institute of Cancer Research (ICR) mouse was established by d-galactose subcutaneous injection. Then, SOD2, p16INK4A and TNF-α were detected by quantitative Real-time PCR (qPCR), Western Blot (WB) and Enzyme-Linked Immunosorbent Assay (ELISA). Simultaneously, senescent cells in livers were stained by hematoxylin and eosin (HE). The viability of splenocytes was detected by Cell Counting Kit-8(CCK-8). The difference in specific immune cells (NK cells, B lymphocytes and T lymphocytes) was detected by flow cytometry. Both low (100 mg/kg) and high (300 mg/kg) concentrations of P. vulgaris treated ageing ICR mice show anti-ageing alterations, such as p16INK4A decreased approximately 1/2 and SOD2 tripled in livers, TNF-α decreased from 1 to 0.6 in plasma, and T cells increased from 0.09 to 0.19%. Compared with the ageing group, the spleen cells in the Prunella-treated group had stronger proliferation ability. Thus, P. vulgaris could have an anti-ageing effect. This is the first study to demonstrate the anti-ageing effect of P. vulgaris. It may also be capable of preventing a variety of age-related diseases.

Single nucleotide polymorphism (SNP) genotyping arrays provide an optimal high-throughput platform for genetic research and molecular breeding programs in both animals and plants. In this study, a high-quality and custom-designed Rice3K56 SNP array was developed with the resequencing data of 3024 rice accessions worldwide, which was then tested extensively in 192 representative rice samples. Printed on the GeneTitan chips of Affymetrix Axiom each containing 56,606 SNP markers, the Rice3K56 array has a high genotyping reliability (99.6%), high and uniform genome coverage (an average of 6.7-kb between adjacent SNPs), abundant polymorphic information and easy automation, compared with previously developed rice SNP arrays. When applied in rice varietal differentiation, population diversity analysis, gene mapping of 13 complex traits by a genome-wide association study analysis (GWAS), and genome selection experiments in a recombinant inbred line and a multi-parent advanced generation inter-cross populations, these properties of the Rice3K56 array were well demonstrated for its power and great potential to be a highly efficient tool for rice genetic research and genomic breeding.

Salinity is a major factor limiting rice productivity, and developing salt-tolerant (ST) varieties is the most efficient approach. Seventy-eight ST introgression lines (ILs), including nine promising lines with improved ST and yield potential (YP), were developed from four BC2F4 populations from inter-subspecific crosses between an elite Geng (japonica) recipient and four Xian (indica) donors at the Institute of Crop Sciences, Chinese Academy of Agricultural Sciences. Genome-wide characterization of donor introgression identified 35 ST QTLs, 25 of which harbor 38 cloned ST genes as the most likely QTL candidates. Thirty-four are Xian-Geng differentiated ones with the donor (Xian) alleles associated with ST, suggesting differentiated responses to salt stress were one of the major phenotypic differences between the two subspecies. At least eight ST QTLs and many others affecting yield traits were identified under salt/non-stress conditions. Our results indicated that the Xian gene pool contains rich ‘hidden’ genetic variation for developing superior Geng varieties with improved ST and YP, which could be efficiently exploited by selective introgression. The developed ST ILs and their genetic information on the donor alleles for ST and yield traits would provide a useful platform for developing superior ST and high-yield Geng varieties through breeding by design in the future.

Objective: To explore and construct a 3D bone remodeling research model displaying stability, repeatability, and precise simulation of the physiological and biochemical environment in vivo.Methods: In this study, 3D bioprinting was used to construct a bone reconstruction model. Sodium alginate (SA), hydroxyapatite (HA) and gelatin (Gel) were mixed into hydrogel as scaffold material. The osteoblast precursor cells MC3T3-E1 and osteoclast precursor cells RAW264.7 were used as seed cells, which may or may not be separated by polycarbonate membrane. The cytokines osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) were used to induce cell differentiation. The function of scaffolds in the process of bone remodeling was analyzed by detecting the related markers of osteoblasts (alkaline phosphatase, ALP) and osteoclasts (tartrate resistant acid phosphatase, TRAP).Results: The scaffold showed good biocompatibility and low toxicity. The surface morphology aided cell adhesion and growth. The scaffold had optimum degradability, water absorption capacity and porosity, which are in line with the conditions of biological experiments. The effect of induced differentiation of cells was the best when cultured alone. After direct contact between the two types of cells at 2D or 3D level, the induced differentiation of cells was inhibited to varying degrees, although they still showed osteogenesis and osteoclast. After the cells were induced by indirect contact culture, the effect of induced differentiation improved when compared with direct contact culture, although it was still not as good as that of single culture. On the whole, the effect of inducing differentiation at 3D level was the same as that at 2D level, and its relative gene expression and enzyme activity were higher than that in the control group. Hence the scaffold used in this study could induce osteogenesis as well as osteoclast, thereby rendering it more effective in inducing new bone formation.Conclusion: This method can be used to construct the model of 3D bone remodeling mechanism.

A significant number of ancient landslides with double or multi-sliding zones exist in reservoir areas. However, understanding large-scale reservoir landslides with double-sliding zones remains limited due to the challenges of studying deformation along the sliding zone independently from surface deformation. In this study, the seepage and deformation characteristics of the Taping landslide were obtained through field investigations and long-term in-situ monitoring. For the first time, hydrological factors influencing double-sliding zones were revealed using an attribute reduction algorithm based on long-term field data. The results indicate that the Taping landslide undergoes significant step-like consistent creep deformation, exhibiting failure along double-sliding zones. For the toe part, reservoir water level (RWL) and precipitation are two critical hydrological factors triggering deformation. Shallow sliding is more susceptible to rainfall, while the deep sliding zone is more affected by RWL variations. In the rear part, precipitation has a greater impact than RWL. Daily precipitation is the primary hydrological factor affecting slope movement along the shallow sliding zone. However, accumulated precipitation over the previous seven days is the most crucial factor influencing slope movement along the deep sliding zone. During the RWL drawdown period, shallow sliding initially occurs at the toe, induced by the de-buttressing effect, while deep sliding occurs after the RWL reaches 145 m, induced by the downslope seepage force. Local damage and failure at the toe provide space for the instability of the rear part, reducing the anti-sliding force. Consequently, failure extends to the rear part. The findings of this study hold significant implications for gaining a deeper understanding of the deformation mechanisms of large-scale reservoir landslides with double-sliding zones and improving landslide management and mitigation strategies in reservoir area.

Background: Previous study confirmed that both TaohongSiwu decoction (THSWD) and Dubosiella newyorkensis improved hypertension-induced endothelial dysfunction. However, the mechanism of THSWD combined with Dubosiella newyorkensis remains unclear. Purpos: e: We aimed to investigate the microecological mechanism underlying the THSWD combined with Dubosiella newyorkensis for the prevention of hypertensive vascular endothelial dysfunction. Methods: Eight percent high-salt diet was applied to induce hypertension in a mouse model for 4 weeks. THSWD, Dubosiella newyorkensis and THSWD combined with Dubosiella newyorkensis were used to intervene in the model mice to observe the changes of systolic blood pressure (SBP), body weight, blood routine, endothelial function, gut contents microbiota and bile acid metabolites. Results: Results revealed that THSWD combined with Dubosiella newyorkensis significantly restored blood pressure and regulated body weight, and markedly downregulating serum and vascular levels of endothelin-1 (ET-1), thrombin regulatory protein (TM), vascular hemophilia factor (vWF) and vascular endothelial growth factor (VEGF), and upregulating nitric oxide (NO) levels compared with the model group. Notably, It altered the diversity and community structure of gut contents microbiota in mice. Lactobacillus and Allobaculum was enormously up-regulated at the genus level. Serum bile acid differential metabolites cholic acid and chenodeoxycholic acid were markedly altered. Futhermore, there was a close relationship between Lactobacillus, Allobaculum and endothelial function indexes in mice. Conclusion: Lactobacillus and Allobaculum play important roles in the prevention of vascular endothelial dysfunction in hypertension during the THSWD combined with Dubosiella newyorkensis.