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Abstract Resolving the detailed structures of metal organic frameworks is of great significance for understanding their structure-property relation. Real-space imaging methods could exhibit superiority in revealing not only the local structure but also the bulk symmetry of these complex porous materials, compared to reciprocal-space diffraction methods, despite the technical challenges. Here we apply a low-dose imaging technique to clearly resolve the atomic structures of building units in a metal-organic framework, MIL-125. An unexpected node structure is discovered by directly imaging the rotation of Ti-O nodes, different from the unrotated structure predicted by previous X-ray diffraction. The imaged structure and symmetry can be confirmed by the structural simulations and energy calculations. Then, the distribution of node rotation from the edge to the center of a MIL-125 particle is revealed by the image analysis of Ti-O rotation. The related defects and surface terminations in MIL-125 are also investigated in the real-space images. These results not only unraveled the node symmetry in MIL-125 with atomic resolution but also inspired further studies on discovering more unpredicted structural changes in other porous materials by real-space imaging methods.

Species belonging to the genus Goniogryllus Chopard, 1936 are primarily identified based on their morphological characteristics. However, male genitalia provide limited features for classification. In this study, we sequenced the COI gene from 49 samples, and reconstructed a phylogenetic tree. Species were classified by a combination of molecular and morphological data, and some morphological features were re-evaluated. The results indicate that the presence or absence of pubescence on the thorax and abdomen, yellow stripes on the head with or without bifurcation, and the color of the maxillary palpus are interspecific differences. The classification based on these morphological features are consistent with the classification based on COI gene. In contrast, variations in the color of the hind femur, pronotum, and the number of dorsal spurs on the hind tibia are considered to be intraspecific variations. Additionally, Qingryllus striofemorus Chen & Zheng, 1995 and Q. jiguanshanensis Liu, Zhang & Shi, 2017 are recognized as the long-wing forms of G. ovalatus Chen & Zheng, 1996. Therefore, Qingryllus Chen & Zheng, 1995 syn. is a junior synonym of Goniogryllus. Q. striofemorus syn. nov. and Q. jiguanshanensis syn. nov. are junior synonyms of G. ovalatus. Furthermore, G. cirilinearis Xie, 2005 syn. nov. is a junior synonym of G. atripalpulus Chen & Zheng, 1996. G. octospinatus Chen & Zheng, 1995 syn. nov. is a junior synonym of G. chongqingensis Chen & Zheng, 1995. Lastly, Callogryllus yunnanus Wu & Zheng, 1992 is transferred to the genus Goniogryllus, as Goniogryllus yunnanus comb. nov.

Abstract Background It’s unclear if excess visceral adipose tissue (VAT) mass in individuals with prediabetes can be countered by adherence to a Mediterranean lifestyle (MEDLIFE). We aimed to examine VAT mass, MEDLIFE adherence, and their impact on type 2 diabetes (T2D) and diabetic microvascular complications (DMC) in individuals with prediabetes. Methods 11,267 individuals with prediabetes from the UK Biobank cohort were included. VAT mass was predicted using a non-linear model, and adherence to the MEDLIFE was evaluated using the 25-item MEDLIFE index, encompassing categories such as “Mediterranean food consumption,” “Mediterranean dietary habits,” and “Physical activity, rest, social habits, and conviviality.” Both VAT and MEDLIFE were categorized into quartiles, resulting in 16 combinations. Incident cases of T2D and related DMC were identified through clinical records. Cox proportional-hazards regression models were employed to examine associations, adjusting for potential confounding factors. Results Over a median follow-up of 13.77 years, we observed 1408 incident cases of T2D and 714 cases of any DMC. High adherence to the MEDLIFE, compared to the lowest quartile, reduced a 16% risk of incident T2D (HR: 0.84, 95% CI: 0.71–0.98) and 31% for incident DMC (0.69, 0.56–0.86). Conversely, compared to the lowest quartile of VAT, the highest quartile increased the risk of T2D (5.95, 4.72–7.49) and incident any DMC (1.79, 1.36–2.35). We observed an inverse dose-response relationship between MEDLIFE and T2D/DMC, and a dose-response relationship between VAT and all outcomes (P for trend

Abstract Background Helicobacter pylori (H. pylori) is the predominant etiological agent of gastritis and disrupts the integrity of the gastric mucosal barrier through various pathogenic mechanisms. After H. pylori invades the gastric mucosa, it interacts with immune cells in the lamina propria. Macrophages are central players in the inflammatory response, and H. pylori stimulates them to secrete a variety of inflammatory factors, leading to the chronic damage of the gastric mucosa. Therefore, the study aims to explore the mechanism of gastric mucosal injury caused by inflammatory factors secreted by macrophages, which may provide a new mechanism for the development of H. pylori-related gastritis. Methods The expression and secretion of CCL3 from H. pylori infected macrophages were detected by RT-qPCR, Western blot and ELISA. The effect of H. pylori-infected macrophage culture medium and CCL3 on gastric epithelial cells tight junctions were analyzed by Western blot, immunofluorescence and transepithelial electrical resistance. EdU and apoptotic flow cytometry assays were used to detect cell proliferation and apoptosis levels. Dual-luciferase reporter assays and chromatin immunoprecipitation assays were used to study CCL3 transcription factors. Finally, gastric mucosal tissue inflammation and CCL3 expression were analyzed by hematoxylin and eosin staining and immunohistochemistry. Results After H. pylori infection, CCL3 expressed and secreted from macrophages were increased. H. pylori-infected macrophage culture medium and CCL3 disrupted gastric epithelial cells tight junctions, while CCL3 neutralizing antibody and receptor inhibitor of CCL3 improved the disruption of tight junctions between cells. In addition, H. pylori-infected macrophage culture medium and CCL3 recombinant proteins stimulated P38 phosphorylation, and P38 phosphorylation inhibitor improved the disruption of tight junctions between cells. Besides, it was identified that STAT1 was a transcription factor of CCL3 and H. pylori stimulated macrophage to secret CCL3 through the JAK1-STAT1 pathway. Finally, after mice were injected with murine CCL3 recombinant protein, the gastric mucosal injury and inflammation were aggravated, and the phosphorylation level of P38 was increased. Conclusions In summary, our findings demonstrate that H. pylori infection stimulates macrophages to secrete CCL3 via the JAK1-STAT1 pathway. Subsequently, CCL3 damages gastric epithelial tight junctions through the phosphorylation of P38. This may be a novel mechanism of gastric mucosal injury in H. pylori-associated gastritis.

Abstract The directional transformation of carbon dioxide (CO2) with renewable hydrogen into specific carbon-heavy products (C6+) of high value presents a sustainable route for net-zero chemical manufacture. However, it is still challenging to simultaneously achieve high activity and selectivity due to the unbalanced CO2 hydrogenation and C–C coupling rates on complementary active sites in a bifunctional catalyst, thus causing unexpected secondary reaction. Here we report LaFeO3 perovskite-mediated directional tandem conversion of CO2 towards heavy aromatics with high CO2 conversion (> 60%), exceptional aromatics selectivity among hydrocarbons (> 85%), and no obvious deactivation for 1000 hours. This is enabled by disentangling the CO2 hydrogenation domain from the C-C coupling domain in the tandem system for Iron-based catalyst. Unlike other active Fe oxides showing wide hydrocarbon product distribution due to carbide formation, LaFeO3 by design is endowed with superior resistance to carburization, therefore inhibiting uncontrolled C–C coupling on oxide and isolating aromatics formation in the zeolite. In-situ spectroscopic evidence and theoretical calculations reveal an oxygenate-rich surface chemistry of LaFeO3, that easily escape from the oxide surface for further precise C–C coupling inside zeolites, thus steering CO2-HCOOH/H2CO-Aromatics reaction pathway to enable a high yield of aromatics.

Abstract By 2060, an estimated one in four Americans will be elderly. Consequently, the prevalence of osteoporosis and fragility fractures will also increase. Presently, no available intervention definitively prevents or manages osteoporosis. This study explores whether Pool 7 Compound 3 (P7C3) reduces progressive bone loss and fragility following the onset of ovariectomy (OVX)‐induced osteoporosis. Results confirm OVX‐induced weakened, osteoporotic bone together with a significant gain in adipogenic body weight. Treatment with P7C3 significantly reduced osteoclastic activity, bone marrow adiposity, whole‐body weight gain, and preserved bone area, architecture, and mechanical strength. Analyses reveal significantly upregulated platelet derived growth factor‐BB and leukemia inhibitory factor, with downregulation of interleukin‐1 R6, and receptor activator of nuclear factor kappa‐B (RANK). Together, proteomic data suggest the targeting of several key regulators of inflammation, bone, and adipose turnover, via transforming growth factor‐beta/SMAD, and Wingless‐related integration site/be‐catenin signaling pathways. To the best of the knowledge, this is first evidence of an intervention that drives against bone loss via RANK. Metatranscriptomic analyses of the gut microbiota show P7C3 increased Porphyromonadaceae bacterium, Candidatus Melainabacteria, and Ruminococcaceae bacterium abundance, potentially contributing to the favorable inflammatory, and adipo‐osteogenic metabolic regulation observed. The results reveal an undiscovered, and multifunctional therapeutic strategy to prevent the pathological progression of OVX‐induced bone loss.

Abstract Background Universal stress proteins (USPs) are a class of stress-induced proteins that play a crucial role in biotic and abiotic stress responses. These proteins have previously been reported to participate directly in responses to various stress and protect plants against unfavorable environmental conditions. However, there is limited research on USPs in cotton, and systematic characterization of USPs in Gossypium species is lacking. Results In the present study, the USP genes in Gossypium hirsutum were systematically identified and classified into six distinct subfamilies. The expansion of USPs in Gossypium species is mainly caused by dispersed duplication and whole genome duplication. Notably, the USPs that have expanded through allotetraploidization events are highly conserved in the allotetraploid species. The promoter regions of GhUSPs contain a diverse range of cis-acting elements associated with stress response. The RNA-Seq analysis and RT-qPCR assays revealed a significant induction of numerous GhUSPs expressions in response to various abiotic stresses. The co-expression network of GhUSPs revealed their involvement in stress response. Conclusions This study systematically analyzed the biological characteristics of GhUSPs and their response to abiotic stress. These findings serve as a theoretical basis for facilitating the breeding of cotton varieties in future research.

Abstract Pressure can alter interatomic distances and its electrostatic interactions, exerting a profound modifying effect on electron orbitals and bonding patterns. Conventional pressure engineering relies on compressions from external sources, which raises significant challenge in precisely applying pressure on individual molecules and also consume substantial mechanical energy. Here we report ultrasmall single-layered NbSe2 flat tubes (

Abstract Background Cotton, being extensively cultivated, holds immense economic significance as one of the most prominent crops globally. The SET (Su(var), E, and Trithorax) domain-containing protein is of significant importance in plant development, growth, and response to abiotic stress by modifying the lysine methylation status of histone. However, the comprehensive identification of SET domain genes (SDG) have not been conducted in upland cotton (Gossypium hirsutum L.). Results A total of 229 SDGs were identified in four Gossypium species, including G. arboretum, G. raimondii, G. hirsutum, and G. barbadense. These genes could distinctly be divided into eight groups. The analysis of gene structure and protein motif revealed a high degree of conservation among the SDGs within the same group. Collinearity analysis suggested that the SDGs of Gossypium species and most of the other selected plants were mainly expanded by dispersed duplication events and whole genome duplication (WGD) events. The allopolyploidization event also has a significant impact on the expansion of SDGs in tetraploid Gossypium species. Furthermore, the characteristics of these genes have been relatively conserved during the evolution. Cis-element analysis revealed that GhSDGs play a role in resistance to abiotic stresses and growth development. Furthermore, the qRT-PCR results have indicated the ability of GhSDGs to respond to salt stress. Co-expression analysis revealed that GhSDG51 might co-express with genes associated with salt stress. In addition, the silencing of GhSDG51 in cotton by the virus-induced gene silencing (VIGS) method suggested a potential positive regulatory role of GhSDG51 in salt stress. Conclusions The results of this study comprehensively analyze the SDGs in cotton and provide a basis for understanding the biological role of SDGs in the stress resistance in upland cotton.

Highlights Influence of interface conductive network on ionic transport and mechanical stability under fast charging is explored for the first time. The mitigation of interface polarization is precisely revealed by the combination of 2D modeling simulation and Cryo-TEM observation, which can be attributed to a higher fraction formation of conductive inorganic species in bilayer SEI, and primarily contributes to a linear decrease in ionic diffusion energy barrier. The improved stress dissipation presented by AFM and Raman shift is critical for the linear reduction in electrode residual stress and thickness swelling. Abstract Progress in the fast charging of high-capacity silicon monoxide (SiO)-based anode is currently hindered by insufficient conductivity and notable volume expansion. The construction of an interface conductive network effectively addresses the aforementioned problems; however, the impact of its quality on lithium-ion transfer and structure durability is yet to be explored. Herein, the influence of an interface conductive network on ionic transport and mechanical stability under fast charging is explored for the first time. 2D modeling simulation and Cryo-transmission electron microscopy precisely reveal the mitigation of interface polarization owing to a higher fraction of conductive inorganic species formation in bilayer solid electrolyte interphase is mainly responsible for a linear decrease in ionic diffusion energy barrier. Furthermore, atomic force microscopy and Raman shift exhibit substantial stress dissipation generated by a complete conductive network, which is critical to the linear reduction of electrode residual stress. This study provides insights into the rational design of optimized interface SiO-based anodes with reinforced fast-charging performance.

This paper aims to explore the relationship between Karl Marx's concept of justice and Martha Nussbaum's capabilities approach. Nusbaum follows the Aristotelian idea of man as a political animal, which is intrinsically consistent with Marx's view of human nature, but she provides us with a new normative perspective to reconsider Marxism. When she initially began to design the list of core capabilities, Nussbaum stated that her capabilities approach originated from Marx's idea of 'genuinely human functions', which requires society to provide a reasonable political arrangement so that humans have the ability to obtain real freedom. Her approach relies on Marx's early understanding of 'human flourishing', and it is also influenced by Marx's ideas about 'the theory of need' and 'the theory of alienation'. From this point of view, Nussbaum's capability theory of justice reveals different aspects of Marx's understanding of justice.

Abstract Phase transition dynamics are an important concern in the wide applications of metal halide perovskites, which fundamentally determine the optoelectronic properties and stabilities of perovskite materials and devices. However, a more in-depth understanding of such a phase transition process with real atomic resolution is still limited by the immature low-dose electron microscopy and in situ imaging studies to date. Here, we apply an emergent low-dose imaging technique to identify different phase structures (α, β and γ) in CsPbI3 nanocrystals during an in-situ heating process. The rotation angles of PbI6 octahedrons can be measured in these images to quantitatively describe the thermal-induced phase distribution and phase transition. Then, the dynamics of such a phase transition are studied at a macro time scale by continuously imaging the phase distribution in a single nanocrystal. The structural evolution process of CsPbI3 nanocrystals at the particle level, including the changes in morphology and composition, is also visualized with increasing temperature. These results provide atomic insights into the transition dynamics of perovskite phases, indicating a long-time transition process with obvious intermediate states and spatial distribution that should be generally considered in the further study of structure-property relations and device performance.

Abstract Salmonella is one of the most common zoonotic foodborne pathogens and can cause serious threats to public health and global economy. A dual‐mode biosensing platform was demonstrated based on cascaded signal amplification coupled with DNA‐functionalized Ag2S NPs@PB (Ag2S NPs@PB‐DNA) for ultrasensitive and selective Salmonella detection. Specifically, once Salmonella was recognized and captured by the control probe, the primer was released to trigger rolling circle amplification and generate a multimeric single‐stranded DNA (ssDNA) with repetitive sequences. The ssDNA could form multicomponent nucleic acid enzyme with cleavage activity to destroy multiple pieces of L‐DNA, achieving cascaded signal amplification and cleaving L‐DNA as a linker between DNA‐functionalized magnetite microspheres (MMs@DNA) and Ag2S NPs@PB‐DNA, leading to reduction in the capture of Ag2S NPs@PB by MMs@DNA. Due to the excellent photothermal properties of Ag2S NPs@PB under near‐infrared irradiation, the changes of temperature and pressure could be simultaneously monitored in the detection system, and the dual‐mode biosensing platform showed outstanding sensitivity, with a limit of the detection value of 100 CFU mL−1 in temperature and 101 CFU mL−1 in pressure. Moreover, the developed biosensing platform could successfully detect 5.7 CFU of Salmonella in spiked chicken breast after 4 h of enrichment. All the results show this study provides a new avenue for specific, sensitive, and convenient bacterial detection in food analysis and environment safety.

Abstract In this study, the change law of the surface subsidence coefficient under the condition of thick coal seam layered mining was investigated. The study is based on the measured subsidence data of the 1210-working face of the Mengba mine surface mobile observation station after the first- and second-layer mining. UDEC numerical simulation software was used to simulate the variation of surface subsidence coefficient after the first, second, third, fourth, fifth-, and sixth-layer mining when the thickness of slicing mining is 5 m. The maximum relative error between the simulated result and the measured result of the subsidence coefficient q is 2.7%, which further verifies the correctness of the established model. Moreover, the simulation results show that with the increase of the cumulative mining thickness, the subsidence coefficient q of the surface presents a segmented characteristic. When the cumulative mining thickness does not reach 25 m, the subsidence coefficient of the surface gradually increases with the increase of the mining thickness. On the other hand, when the cumulative mining thickness reaches 25 m, the subsidence coefficient of the surface will tend to a constant value and no longer change with the increase of the mining thickness. Finally, the calculation formula between the surface subsidence coefficient and the cumulative mining thickness of layered mining under the condition of medium hard roof is fitted, which provides a parameter basis for coal seam mining with similar geological conditions.

The coupling between solar wind and the magnetosphere and the dynamic processes in geo-space are the basic driving factors of space weather. Understanding these processes on the system level is essential to the studies of space physics and space weather. Recent solar wind charge exchange (SWCX) X-ray emission discoveries provide a novel approach to detect the large-scale magnetosphere through soft X-ray imaging. SWCX occurs when high-charge heavy ions such as C6+, N7+, O7+, and O8+ in the solar wind interact with neutral atoms or molecules, such as neutral hydrogen atoms in near-Earth space, neutral hydrogen and helium atoms in the heliosphere, and H2O and CO2 molecules on comets and other planets. Solar wind ions become excited by receiving one or more electrons, and then return to the ground state by releasing one or more photons in the soft X-ray band. The characteristics of the SWCX emissions include the X-ray spectrum showing line emissions corresponding to different species of solar wind particles and neutrons, and fast time variations closely related to solar wind variations. The SWCX soft X-ray emission of the Earth's magnetosphere mainly occurs in the magnetosheath on the dayside and the cusp regions. Therefore, the magnetosphere can be remotely imaged using large-scale soft X-ray imaging technology, allowing the fundamental modes of the interaction between the solar wind and magnetosphere to be recognized on a systematic scale.In this context, the European Space Agency (ESA) and Chinese Academy of Sciences (CAS) jointly proposed the Solar wind Magnetosphere Ionosphere Link Explorer (SMILE). SMILE was approved in 2016 and implemented thereafter. SMILE aims to provide remote sensing measurements of the magnetopause and bow shock around the subsolar region, part of the cusp regions, and the aurora, as well as simultaneous in situ observations of the solar wind plasma and magnetic field. SMILE is planned to be launched in 2024–2025. Other missions have also been proposed to image the Earth's magnetosphere, such as the GEOspace X-ray imager (GEO-X) in Japan, Lunar Environment heliospherics X-ray Imager (LEXI) in the United States, and Lunar-based soft X-ray imager (LSXI) in China.With the advent of soft X-ray imaging missions to detect the magnetopause, evaluating the expected soft X-ray images and developing appropriate techniques to extract 3-dimentional boundary information from the 2-dimentional images is essential. Global magnetohydrodynamic (MHD) and instrument simulations are used to generate expected X-ray images under different solar wind conditions with different viewing geometries. Based on these images, several approaches have been developed to analyze the signals, composing the 'arsenal' or 'toolkit' for magnetopause reconstruction. Each approach has its own advantages and disadvantages, applicable to different situations.This paper introduces the mechanism of magnetospheric X-ray emission, reviews the research on the observational evidence and characteristics of SWCX X-ray emissions, summarizes the progress of simulation studies, presents the missions (or concept) of the magnetospheric X-ray detection, and discusses the possibility of future implementation of X-ray imaging for detecting other planets.

Based on the bosonization approach, the supersymmetric Boussinesq equation is converted into a coupled bosonic system. The symmetry group and the commutation relations of the corresponding bosonic system are determined through the Lie point symmetry theory. The group invariant solutions of the coupled bosonic system are analyzed by the symmetry reduction technique. Special traveling wave solutions are generated by using the mapping and deformation method. Some novel solutions, such as multi-soliton, soliton–cnoidal interaction solutions, and lump waves, are given by utilizing the Hirota bilinear and the consistent tanh expansion methods. The methods in this paper can be effectively expanded to study rich localized waves for other supersymmetric systems.

Abstract Carbon nanomaterials are unique with excellent functionality and diverse structures. However, agglomerated structures are commonly formed because of small‐size effects and surface effects. Their hierarchical assembly into micro particles enables carbon nanomaterials to break the boundaries of classical Geldart particle classification before stable fluidization under gas‐solid interactions. Currently, there are few systematic reports regarding the structural evolution and fluidization mechanism of carbon nano agglomerations. Based on existing research on carbon nanomaterials, this article reviews the fluidized structure control and fluidization principles of prototypical carbon nanotubes (CNTs) as well as their nanocomposites. The controlled agglomerate fluidization technology leads to the successful mass production of agglomerated and aligned CNTs. In addition, the self‐similar agglomeration of individual ultralong CNTs and nanocomposites with silicon as model systems further exemplify the important role of surface structure and particle‐fluid interactions. These emerging nano agglomerations have endowed classical fluidization technology with more innovations in advanced applications like energy storage, biomedical, and electronics. This review aims to provide insights into the connections between fluidization and carbon nanomaterials by highlighting their hierarchical structural evolution and the principle of agglomerated fluidization, expecting to showcase the vitality and connotation of fluidization science and technology in the new era.

Abstract Background Phloem protein 2 (PP2) proteins play a vital role in the Phloem-based defense (PBD) and participate in many abiotic and biotic stress. However, research on PP2 proteins in cotton is still lacking. Results A total of 25, 23, 43, and 47 PP2 genes were comprehensively identified and characterized in G.arboretum, G.raimondii, G.barbadense, and G.hirsutum. The whole genome duplication (WGD) and allopolyploidization events play essential roles in the expansion of PP2 genes. The promoter regions of GhPP2 genes contain many cis-acting elements related to abiotic stress and the weighted gene co-expression network analysis (WGCNA) analysis displayed that GhPP2s could be related to salt stress. The qRT-PCR assays further confirmed that GhPP2-33 could be dramatically upregulated during the salt treatment. And the virus-induced gene silencing (VIGS) experiment proved that the silencing of GhPP2-33 could decrease salt tolerance. Conclusions The results in this study not only offer new perspectives for understanding the evolution of PP2 genes in cotton but also further explore their function under salt stress.

Abstract Metal-organic frameworks (MOFs) with different functional groups have wide applications, while the understanding of functionalization influences remains insufficient. Previous researches focused on the static changes in electronic structure or chemical environment, while it is unclear in the aspect of dynamic influence, especially in the direct imaging of dynamic changes after functionalization. Here we use integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM) to directly ‘see’ the rotation properties of benzene rings in the linkers of UiO-66, and observe the high correlation between local rigidity and the functional groups on the organic linkers. The rigidity is then correlated to the macroscopic properties of CO2 uptake, indicating that functionalization can change the capability through not only static electronic effects, but also dynamic rotation properties. To the best of our knowledge this is the first example of a technique to directly image the rotation properties of linkers in MOFs, which provides an approach to study the local flexibility and paves the way for potential applications in capturing, separation and molecular machine.

Abstract Background Endothelial-mesenchymal transition (EndoMT) is an emerging adaptive process that modulates lymphatic endothelial function to drive aberrant lymphatic vascularization in the tumour microenvironment (TME); however, the molecular determinants that govern the functional role of EndoMT remain unclear. Here, we show that cancer-associated fibroblast (CAF)-derived PAI-1 promoted the EndoMT of lymphatic endothelial cells (LECs) in cervical squamous cell carcinoma (CSCC). Methods Immunofluorescent staining of α-SMA, LYVE-1 and DAPI were examined in primary tumour samples obtained from 57 CSCC patients. Assessment of cytokines secreted by CAFs and normal fibroblasts (NFs) was performed using human cytokine antibody arrays. The phenotype of EndoMT in lymphatic endothelial cells (LECs), gene expression levels, protein secretion and activity of signaling pathways were measured by real-time RT-PCR, ELISA or western blotting. The function of lymphatic endothelial monolayers was examined by transwell, tube formation assay, transendothelial migration assay in vitro. Lymphatic metastasis was measured using popliteal lymph node metastasis model. Furthermore, association between PAI-1 expression and EndoMT in CSCC was analyzed by immunohistochemistry. The Cancer Genome Atlas (TCGA) databases was used to assess the association of PAI-1 with survival rate in CSCC. Results CAF-derived PAI-1 promoted the EndoMT of LECs in CSCC. LECs undergoing EndoMT could initiate tumour neolymphangiogenesis that facilitated cancer cell intravasation/extravasation, which in turn promoted lymphatic metastasis in CSCC. Mechanistically, PAI-1 activated the AKT/ERK1/2 pathways by directly interacting with low-density lipoprotein receptor-related protein (LRP1), thereby leading to elevated EndoMT activity in LECs. Blockade of PAI-1 or inhibition of LRP1/AKT/ERK1/2 abrogated EndoMT and consequently attenuated CAF-induced tumour neolymphangiogenesis. Furthermore, clinical data revealed that increased PAI-1 levels positively correlated with EndoMT activity and poor prognosis in CSCC patients. Conclusion Our data indicate that CAF-derived PAI-1 acts as an important neolymphangiogenesis-initiating molecular during CSCC progression through modulating the EndoMT of LECs, resulting in promotion of metastasis ability in primary site. PAI-1 could serve as an effective prognostic biomarker and therapeutic target for CSCC metastasis.

Abstract Radiotherapy is a critical component of cancer care but can cause osteoporosis and pathological insufficiency fractures in surrounding and otherwise healthy bone. Presently, no effective countermeasure exists, and ionizing radiation-induced bone damage continues to be a substantial source of pain and morbidity. The purpose of this study was to investigate a small molecule aminopropyl carbazole named P7C3 as a novel radioprotective strategy. Our studies revealed that P7C3 repressed ionizing radiation (IR)-induced osteoclastic activity, inhibited adipogenesis, and promoted osteoblastogenesis and mineral deposition in vitro. We also demonstrated that rodents exposed to clinically equivalent hypofractionated levels of IR in vivo develop weakened, osteoporotic bone. However, the administration of P7C3 significantly inhibited osteoclastic activity, lipid formation and bone marrow adiposity and mitigated tissue loss such that bone maintained its area, architecture, and mechanical strength. Our findings revealed significant enhancement of cellular macromolecule metabolic processes, myeloid cell differentiation, and the proteins LRP-4, TAGLN, ILK, and Tollip, with downregulation of GDF-3, SH2B1, and CD200. These proteins are key in favoring osteoblast over adipogenic progenitor differentiation, cell matrix interactions, and shape and motility, facilitating inflammatory resolution, and suppressing osteoclastogenesis, potentially via Wnt/β-catenin signaling. A concern was whether P7C3 afforded similar protection to cancer cells. Preliminarily, and remarkably, at the same protective P7C3 dose, a significant reduction in triple-negative breast cancer and osteosarcoma cell metabolic activity was found in vitro. Together, these results indicate that P7C3 is a previously undiscovered key regulator of adipo-osteogenic progenitor lineage commitment and may serve as a novel multifunctional therapeutic strategy, leaving IR an effective clinical tool while diminishing the risk of adverse post-IR complications. Our data uncover a new approach for the prevention of radiation-induced bone damage, and further work is needed to investigate its ability to selectively drive cancer cell death.

The human skeleton is a metabolically active system that is constantly regenerating via the tightly regulated and highly coordinated processes of bone resorption and formation. Emerging evidence reveals fascinating new insights into the role of sphingolipids, including sphingomyelin, sphingosine, ceramide, and sphingosine-1-phosphate, in bone homeostasis. Sphingolipids are a major class of highly bioactive lipids able to activate distinct protein targets including, lipases, phosphatases, and kinases, thereby conferring distinct cellular functions beyond energy metabolism. Lipids are known to contribute to the progression of chronic inflammation, and notably, an increase in bone marrow adiposity parallel to elevated bone loss is observed in most pathological bone conditions, including aging, rheumatoid arthritis, osteoarthritis, and osteomyelitis. Of the numerous classes of lipids that form, sphingolipids are considered among the most deleterious. This review highlights the important primary role of sphingolipids in bone homeostasis and how dysregulation of these bioactive metabolites appears central to many chronic bone-related diseases. Further, their contribution to the invasion, virulence, and colonization of both viral and bacterial host cell infections is also discussed. Many unmet clinical needs remain, and data to date suggest the future use of sphingolipid-targeted therapy to regulate bone dysfunction due to a variety of diseases or infection are highly promising. However, deciphering the biochemical and molecular mechanisms of this diverse and extremely complex sphingolipidome, both in terms of bone health and disease, is considered the next frontier in the field.

Abstract Polycyclic N-heterocycles are important structural motifs commonly found in bioactive compounds, however, their selective construction via the cyclization of allenynes remains challenging yet highly desirable. Here we show a homogeneous copper-catalyzed hetero Diels−Alder (HDA) reaction of allenynes with cis-diazenes (PTAD, 4-phenyl-1,2,4-triazoline-3,5-dione), allowing the practical and efficient synthesis of a diverse array of valuable polycyclic N-heterocycles. A temperature-controlled and stereocontrolled chemoselectivity of the reaction was observed, leading to the chemodivergent synthesis of tetracyclic pyrrolidines, pentacyclic triazepanes and tricyclic pyrrolidines. Compared with related Au-catalyzed cyclization of allenynes, this copper catalysis achieves cyclization of allenynes terminating in C–N bond formation via the HDA reaction.

Abstract Industrial production of single-chirality carbon nanotubes is critical for their applications in high-speed and low-power nanoelectronic devices, but both their growth and separation have been major challenges. Here, we report a method for industrial separation of single-chirality carbon nanotubes from a variety of raw materials with gel chromatography by increasing the concentration of carbon nanotube solution. The high-concentration individualized carbon nanotube solution is prepared by ultrasonic dispersion followed by centrifugation and ultrasonic redispersion. With this technique, the concentration of the as-prepared individualized carbon nanotubes is increased from about 0.19 mg/mL to approximately 1 mg/mL, and the separation yield of multiple single-chirality species is increased by approximately six times to the milligram scale in one separation run with gel chromatography. When the dispersion technique is applied to an inexpensive hybrid of graphene and carbon nanotubes with a wide diameter range of 0.8–2.0 nm, and the separation yield of single-chirality species is increased by more than an order of magnitude to the sub-milligram scale. Moreover, with present separation technique, the environmental impact and cost of producing single-chirality species are greatly reduced. We anticipate that this method promotes industrial production and practical applications of single-chirality carbon nanotubes in carbon-based integration circuits.

Abstract Background Epicardial adipose tissue (EAT) has been suggested to exert deleterious effects on myocardium and cardiovascular disease (CVD) consequence. We evaluated the associations of EAT thickness with adverse outcomes and its potential mediators in the community. Methods Participants without heart failure (HF) who had undergone cardiac magnetic resonance (CMR) to measure EAT thickness over the right ventricular free wall from the Framingham Heart Study were included. The correlation of EAT thickness with 85 circulating biomarkers and cardiometric parameters was assessed in linear regression models. The occurrence of HF, atrial fibrillation, coronary heart disease (CHD), and other adverse events was tracked since CMR was implemented. Their associations with EAT thickness and the mediators were evaluated using Cox regression and causal mediation analysis. Results Of 1554 participants, 53.0% were females. Mean age, body mass index, and EAT thickness were 63.3 years, 28.1 kg/m2, and 9.8 mm, respectively. After fully adjusting, EAT thickness positively correlated with CRP, LEP, GDF15, MMP8, MMP9, ORM1, ANGPTL3, and SERPINE1 and negatively correlated with N-terminal pro-B-type natriuretic peptide (NT-proBNP), IGFBP1, IGFBP2, AGER, CNTN1, and MCAM. Increasing EAT thickness was associated with smaller left ventricular end-diastolic dimension, thicker left ventricular wall thickness, and worse global longitudinal strain (GLS). During a median follow-up of 12.7 years, 101 incident HF occurred. Per 1-standard deviation increment of EAT thickness was associated with a higher risk of HF (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.19–1.72, P

Abstract Due to the rise in our aging population, a disproportionate demand for total joint arthroplasty (TJA) in the elderly is forecast. Periprosthetic joint infection (PJI) represents one of the most challenging complications that can occur following TJA, and as the number of primary and revision TJAs continues to rise, an increasing PJI burden is projected. Despite advances in operating room sterility, antiseptic protocols, and surgical techniques, approaches to prevent and treat PJI remain difficult, primarily due to the formation of microbial biofilms. This difficulty motivates researchers to continue searching for an effective antimicrobial strategy. The dextrorotatory-isoforms of amino acids (D-AAs) are essential components of peptidoglycan within the bacterial cell wall, providing strength and structural integrity in a diverse range of species. Among many tasks, D-AAs regulate cell morphology, spore germination, and bacterial survival, evasion, subversion, and adhesion in the host immune system. When administered exogenously, accumulating data have demonstrated that D-AAs play a pivotal role against bacterial adhesion to abiotic surfaces and subsequent biofilm formation; furthermore, D-AAs have substantial efficacy in promoting biofilm disassembly. This presents D-AAs as promising and novel targets for future therapeutic approaches. Despite their emerging antibacterial efficacy, their role in disrupting PJI biofilm formation, the disassembly of established TJA biofilm, and the host bone tissue response remains largely unexplored. This review aims to examine the role of D-AAs in the context of TJAs. Data to date suggest that D-AA bioengineering may serve as a promising future strategy in the prevention and treatment of PJI.

The disability, mortality and costs due to ionizing radiation (IR)-induced osteoporotic bone fractures are substantial and no effective therapy exists. Ionizing radiation increases cellular oxidative damage, causing an imbalance in bone turnover that is primarily driven via heightened activity of the bone-resorbing osteoclast. We demonstrate that rats exposed to sublethal levels of IR develop fragile, osteoporotic bone. At reactive surface sites, cerium ions have the ability to easily undergo redox cycling: drastically adjusting their electronic configurations and versatile catalytic activities. These properties make cerium oxide nanomaterials fascinating. We show that an engineered artificial nanozyme composed of cerium oxide, and designed to possess a higher fraction of trivalent (Ce3+) surface sites, mitigates the IR-induced loss in bone area, bone architecture, and strength. These investigations also demonstrate that our nanozyme furnishes several mechanistic avenues of protection and selectively targets highly damaging reactive oxygen species, protecting the rats against IR-induced DNA damage, cellular senescence, and elevated osteoclastic activity in vitro and in vivo. Further, we reveal that our nanozyme is a previously unreported key regulator of osteoclast formation derived from macrophages while also directly targeting bone progenitor cells, favoring new bone formation despite its exposure to harmful levels of IR in vitro. These findings open a new approach for the specific prevention of IR-induced bone loss using synthesis-mediated designer multifunctional nanomaterials.

An extended (2+1)-dimensional shallow water wave (SWW) model governs the evolution of nonlinear shallow water wave propagation in two spatial and a temporal coordinate. The multi-linear variable separation approach is applied to the SWW equation. The variable separation solution consisting of two arbitrary functions is given. By choosing the arbitrary functions as the exponential and trigonometric forms, some novel fission and fusion phenomena including the semifoldons, peakons, lump, dromions and periodic waves are graphically and analytically studied. The results enhance the variety of the dynamics of the nonlinear wave fields related by engineering and mathematical physics.

BackgroundHepatocellular carcinoma (HCC) has a high prevalence and poor prognosis worldwide. Therefore, it is urgent to find effective and timely diagnostic markers. The objective of this study was to evaluate the diagnostic value of F-box protein 43 promoter methylation in peripheral blood mononuclear cells (PBMCs) for HCC.MethodA total of 247 participants were included in this study, comprising individuals with 123 hepatitis B virus-associated HCC, 79 chronic hepatitis B, and 45 healthy controls. F-box protein 43 methylation and mRNA levels in PBMCs were detected by MethyLight and quantitative real-time PCR.ResultF-box protein 43 promoter methylation levels were significantly lower in HCC PBMCs than the chronic hepatitis B (P < 0.001) and healthy control PBMCs (P < 0.001). Relative mRNA expression levels of F-box protein 43 in HCC PBMCs were significantly higher than those in chronic hepatitis B (P < 0.001) and healthy control PBMCs (P < 0.001). Receiver operating characteristic analysis of F-box protein 43 promoter methylation levels yielded an area under curve (AUC) of 0.793 with 76.42% sensitivity and 68.35% specificity when differentiating HCC from chronic hepatitis. These values for the F-box protein 43 promoter methylation level were superior to those of the alpha-fetoprotein serum (AFP) level (AUC: 0.780, sensitivity: 47.97%, and specificity: 96.20%), with increments in values for the combination of F-box protein 43 promoter methylation AFP levels (AUC: 0.888, sensitivity: 76.42%, and specificity: 86.08%).ConclusionHypomethylation of the F-box protein 43 promoter in PBMCs is a promising biochemical marker for HBV-associated HCC.

Background: Steroid-induced Osteonecrosis of the Femoral Head (SIONFH) is a skeletal disease with a high incidence and a poor prognosis. Whole body vibration therapy (WBVT), a new type of physical training, is known to promote bone formation. However, it remains unclear whether WBVT has a therapeutic effect on SIONFH.Materials and methods: Thirty adult male and female Sprague-Dawley (SD) rats were selected and randomly assigned to three experimental groups: the control group, the model group, and the mechanical vibration group, respectively. SIONFH induction was achieved through the combined administration of lipopolysaccharides (LPS) and methylprednisolone sodium succinate for injection (MPS). The femoral head samples underwent hematoxylin and eosin (H&E) staining to visualize tissue structures. Structural parameters of the region of interest (ROI) were compared using Micro-CT analysis. Immunohistochemistry was employed to assess the expression levels of Piezo1, BMP2, RUNX2, HIF-1, VEGF, CD31, while immunofluorescence was used to examine CD31 and Emcn expression levels.Results: The H&E staining results revealed a notable improvement in the ratio of empty lacuna in various groups following WBVT intervention. Immunohistochemical analysis showed that the expression levels of Piezo1, BMP2, RUNX2, HIF-1, VEGF, and CD31 in the WBVT group exhibited significant differences when compared to the Model group (p < 0.05). Additionally, immunofluorescence analysis demonstrated statistically significant differences in CD31 and Emcn expression levels between the WBVT group and the Model group (p < 0.05).Conclusion: WBVT upregulates Piezo1 to promote osteogenic differentiation, potentially by enhancing the HIF-1α/VEGF axis and regulating H-vessel angiogenesis through the activation of the Piezo1 ion channel. This mechanism may lead to improved blood flow supply and enhanced osteogenic differentiation within the femoral head.

BackgroundHepatoblastoma (HB) is the most common liver tumor in children with easy metastasis. The emergence of ferroptosis as a novel form of cell death has gained increased attention in various human cancers. However, the roles of ferroptosis-related (FR) genes in HB remain elusiveMethodsThe GSE133039, GSE131329, and GSE81928 datasets were utilized for screening core FR genes in HB. Through Lasso regression analysis and using the support vector machine recursive feature elimination (SVM-RFE) algorithm, three candidate FR genes were obtained for characterizing HB. Their expression patterns and their clinical associations were explored through the ‘Limma’ R package, and their diagnostic potential was evaluated using ROC curves. Nitric oxide synthase 2 (NOS2) emerged as a candidate for further analyses. The CIBERSORT algorithm and GSEA dataset were used to respectively investigate the immune and metabolism effects of NOS2; the former was validated through immunofluorescence. The GSDC database was employed to analyze the correlation between NOS2 expression and the therapeutic efficacy of multiple drugs. PCR, Western blotting, colony formation assays, and Transwell experiments, were used to determine biological functions of NOS2 in HB cells. Potential upstream transcription factors of NOS2 were predicted through the TRRUST, hTFtarget, GeneCards, and JASPAR databases.ResultsNQO1, SLC1A4, and NOS2 were identified as potential genes in HB and found to be significantly upregulated in tumor samples. Nevertheless, only NOS2 was closely associated with HB clinicopathological characteristics; high NOS2 expression indicated poor prognosis, metastatic tendency, and late clinical stage. Immune analyses indicated that high NOS2 expression was concomitant with decreased infiltration levels of CD8+ T cells but increased infiltration levels of macrophages. GSEA revealed that NOS2 failed to affect the enrichments of glycolysis, fatty acid metabolism, and cholesterol biosynthesis in HB. Moreover, NOS2 was positively correlated with the IC50 values of trametinib, lapatinib, and cisplatin. NOS2 overexpression promoted the proliferation, migration and invasion of HepG2 and HuH-6 cells. JUND was identified as a potential transcriptional regulator of NOS2 by binding to its promoter (5’-TTCTGACTCTTTT-3’).ConclusionNOS2 plays a significant role in HB clinical assessments and holds promise as a novel therapeutic target.

Cancer-associated fibroblasts (CAFs) are key stromal cells in the tumor microenvironment (TME) that critically contribute to cancer initiation and progression. In bladder cancer (BCa), there is emerging evidence that BCa CAFs are actively involved in cancer cell proliferation, invasion, metastasis, and chemotherapy resistance. This review outlines the present knowledge of BCa CAFs, with a particular emphasis on their origin and function in BCa progression, and provides further insights into their clinical application.

Organic molecules containing seven-membered rings are important structural motifs for drug candidates, but the construction of seven-membered rings can be challenging through traditional cyclization pathways. Here, the authors report a copper-catalyzed alkyne oxidation and Büchner-type ring-expansion to generate benzo[6,7]azepino[2,3-b]quinolines and pyridine-based diones.

Abstract It remains unknown whether systolic (SBP) and diastolic (DBP) pressure on admission are associated with short‐ and long‐term mortality in Chinese patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced (HFrEF) ejection fraction. In 2706 HF patients (39.1% women; mean age, 68.8 years), we assessed the risk of 30‐day, 1‐year, and long‐term (> 1 year) mortality with 1‐SD increment in SBP and DBP, using multivariable logistic and Cox regression, respectively. During a median follow‐up of 4.1 years, 1341 patients died. The 30‐day, 1‐year, and long‐term mortality were 3.5%, 16.7%, and 39.4%, respectively. In multivariable‐adjusted analyses additionally accounted for DBP or SBP, a higher SBP conferred a higher risk of long‐term mortality (hazard ratio, 1.11; 95% CI, 1.02‐1.22; p = .017) and a lower DBP was associated with a higher risk of all types of mortality (p ≤ .011) in all HF patients. Independent of potential confounders including DBP or SBP, in patients with HFpEF, higher SBP and lower DBP levels predicted a higher risk of long‐term mortality with hazard ratios amounting to 1.16 (95% CI, 1.04–1.29; p = .007) and .89 (95% CI, .80–.99; p = .028), respectively. In patients with HFmrEF and HFrEF, irrespective of adjustments of potential confounders, DBP was associated with 1‐year mortality with odds ratios ranging from .49 to .62 (p ≤ .006). In conclusion, lower DBP and higher SBP levels on admission were associated with a higher risk of different types of all‐cause mortality in Chinese patients with different HF subtypes. Our observations highlight that admission BP may help to improve risk stratification.

Context Ganoderma lucidum polysaccharides (GLP), from Ganoderma lucidum (Leyss. ex Fr.) Karst. (Ganodermataceae), are reported to have anti-inflammatory effects, including anti-neuroinflammation and anti-colitis. Nevertheless, the role of GLP in acute pneumonia is unknown.Objective To explore the protective role of GLP against LPS-induced acute pneumonia and investigate possible mechanisms.Materials and methods GLP were extracted and used for high-performance liquid chromatography (HPLC) analysis after acid hydrolysis and PMP derivatization. Sixty C57BL/6N male mice were randomly divided into six groups: Sham, Model, LPS + GLP (25, 50 and 100 mg/kg/d administered intragastrically for two weeks) and LPS + dexamethasone (6 mg/kg/d injected intraperitoneally for one week). Acute pneumonia mouse models were established by intratracheal injection of LPS. Haematoxylin and eosin (H&E) staining was examined to evaluate lung lesions. ELISA and quantitative real-time PCR were employed to assess inflammatory factors expression. Western blots were carried out to measure Neuropilin-1 expression and proteins related to apoptosis and autophagy.Results GLP suppressed inflammatory cell infiltration. In BALF, cell counts were 1.1 × 106 (model) and 7.1 × 105 (100 mg/kg). Release of GM-CSF and IL-6 was reduced with GLP (25, 50 and 100 mg/kg) treatment. The expression of genes IL-1β, IL-6, TNF-α and Saa3 was reduced. GLP treatment also suppressed the activation of Neuropilin-1 (NRP1), upregulated the levels of Bcl2/Bax and LC3 and led to downregulation of the ratio C-Caspase 3/Caspase 3 and P62 expression.Discussion and conclusions GLP could protect against LPS-induced acute pneumonia through multiple mechanisms: blocking the infiltration of inflammatory cells, inhibiting cytokine secretion, suppressing NRP1 activation and regulating pneumonocyte apoptosis and autophagy.