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Background: Periodontitis and bone loss in the maxillofacial and dental areas pose considerable challenges for both functional and aesthetic outcomes. To date, implantable dental barrier membranes, designed to prevent epithelial migration into defects and create a favorable environment for targeted cells, have garnered significant interest from researchers. Consequently, a variety of materials and fabrication methods have been explored in extensive research on regenerative dental barrier membranes., Methods: This review focuses on dental barrier membranes, summarizing the various biomaterials used in membrane manufacturing, fabrication methods, and state-of-the-art applications for dental tissue regeneration. Based on a discussion of the pros and cons of current membrane strategies, future research directions for improved membrane designs are proposed., Results and Conclusion: To endow dental membranes with various biological properties that accommodate different clinical situations, numerous biomaterials and manufacturing methods have been proposed. These approaches provide theoretical support and hold promise for advancements in dental tissue regeneration., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. Ethical statement: This manuscript does not have any content that requires ethical approval., (© 2025. The Author(s).)

Applying external electric fields to mineral surfaces can have a substantial impact on ice nucleation, influencing both climate and atmospheric systems. While earlier studies have demonstrated that electric fields can enhance ice nucleation on nonmineral surfaces, the mechanisms driving heterogeneous ice nucleation (HIN) on mineral surfaces under electric fields with different surface ions remain unclear. In this study, we investigate the ion-specific effects under electric fields on HIN efficiency using mica surfaces containing various cations. Our findings reveal that an upward electric field significantly boosts HIN of water droplets atop Na-mica surfaces, raising the nucleation temperature by approximately 6 °C. In contrast, mica surfaces with other cations or those exposed to a downward electric field show no change in nucleation temperature or HIN efficiency. Molecular dynamics simulations suggest that Na + ions detach more easily from the mica surface under an electric field, exposing more of the flat mica lattice and thus possibly promoting ice nucleation. This study offers new insights into the ion-specific effects of electric fields on HIN, providing a deeper understanding of the role of cations and electric fields in ice nucleation processes.

Polyethylene terephthalate (PET), polystyrene (PS), and polyvinyl chloride (PVC) are the most commonly used polymers in plastic products. Therefore, endowing these polymers with unique optical properties would significantly enhance their overall technological value. Herein, we synthesized a phosphorescent molecule, 2,2'-diphenyl-3,3'-bibenzofuran (DBF), with notable reversible photochromic properties (switching between colorless and deep red) as the guest and constructed a doped system with the above polymers as the hosts. All doped materials exhibited both room-temperature phosphorescence and reversible photochromic properties. The guest molecule exhibited strong reversible cyclization activity and small conformational changes during the reaction process, as well as moderate rigidity of the host matrix, which enabled the uncommon coexistence of these two properties in the doped system. Finally, DBF/PET was successfully formed into a transparent and uniform film with a length of 200 m, a width of 20 cm, a thickness of only 60-70 μm. This film exhibited excellent thermal-stability, sensitivity, and resistance to photo-fatigue, indicating its applicability in industrial production., (© 2025 Wiley-VCH GmbH.)

Introduction: As urbanization progresses and vulnerable populations increase, equitable accessibility remains a critical issue. This study evaluates the accessibility of transit-oriented development (TOD) in Shanghai, focusing on barrier-free facilities in metro stations., Methods: A comprehensive evaluation framework combining the Analytic Hierarchy Process (AHP) and the System Usability Scale (SUS) was developed to assess metro station accessibility. Thirteen evaluation factors formed a composite accessibility index. A case study of two Shanghai metro stations, Xinzhuang and Xujiahui, was conducted using quantitative metrics, surveys, and interviews., Results: A strong correlation between AHP scores and SUS ratings validated the framework's reliability. The study provides recommendations for enhancing metro accessibility., Discussion: The proposed framework offers a robust tool for evaluating and improving urban transit accessibility, with implications for inclusive mobility policy and design., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Zhang, Yang, Jiang, Lu, Li, Rong and Huang.)

Recently, injectable hydrogels have garnered significant attention in tissue engineering due to their controlled flowability, strong plasticity, adaptability, and good biocompatibility. However, research on readily injectable in situ -forming hydrogels capable of forming functional three-dimensional (3D) tissue condensations remains limited. This study explores the development and evaluation of a carboxymethyl chitosan (CMCTS)/oxidized hyaluronic acid (oHA) hydrogel incorporated with silver sulfadiazine (AgSD) for tissue engineering applications with inherent antibacterial activity. Through physicochemical analysis, the optimal formulation of CMCTS/oHA hydrogels was established. The hydrogel demonstrated excellent injectability, enabling minimally invasive in situ delivery. In vitro cytotoxicity assays identified 0.1 % AgSD as the optimal concentration, supporting cell proliferation while exhibiting antimicrobial efficacy against S. mutans and E. faecalis . In vivo studies revealed complete hydrogel degradation and good biocompatibility, with no adverse tissue reactions. The hydrogel's ability to form 3D cell aggregates and support tissue regeneration underscores its potential for future 3D tissue engineering applications. Consequently, the injectable CMCTS/oHA/AgSD hydrogel developed in this study holds significant potential for application in a wide range of bioengineering fields, including antibacterial substance delivery systems and 3D tissue engineering, indicating potential for future clinical application., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors.)

Exploring novel materials with intrinsic self-trapped excitons (STEs) is crucial for advancing optoelectronic technologies. In this study, 2D 3R-phase ZnIn 2 S 4 , featuring broken inversion symmetry , is introduced to investigate intrinsic STEs. This material exhibits a broadband photoluminescence (PL) emission with a full width at half maximum of 164 nm and a large Stokes shift of ≈0.6 eV, which arises from the distortion of [ZnS 4 ] 6- tetrahedral unit induced by the symmetry breaking and strong electron-phonon coupling. The photophysical properties of the STEs exhibit a high Huang-Rhys factor (15.0), rapid STEs formation time (166 fs), and extended STEs lifetime (1039 ps), as demonstrated by experimental evidence from temperature-dependent PL, Raman spectroscopy, and ultrafast absorption spectroscopy. Additionally, STE-induced photoconductive effect is elucidated, indicating that intrinsic STEs in 3R-ZnIn 2 S 4 can provide a synergistic effect that enhances absorption capacity, localization, and lifetime by capturing the self-trapped hole state. Consequently, the 2D 3R-ZnIn 2 S 4 photodetector exhibits remarkable broad-spectrum photosensitivity, including a photo-switching ratio of 11286, response times of less than 0.6 ms, responsivity of 15.2 A W -1 , detectivity of 1.02 × 10¹¹ Jones, and external quantum efficiency of 5032% under 375 nm light. These findings provide new ideas for exploring materials with intrinsic STEs to achieve novel high-performance photodetector applications., (© 2024 Wiley‐VCH GmbH.)

Oocyte meiotic errors can cause infertility, miscarriage, and birth defects. Here the role and the underlying mechanism of p21 activated kinase 4 (PAK4) in mouse oocyte meiosis is evaluated. It is found that PAK4 expression and its phosphorylation are detected in high level at germinal vesicle (GV) stage, and gradually decreased after meiotic resumption in oocytes. PAK4 has direct physical interaction with both mitogen-activated protein kinases 1/2 (MEK1/2) and Paxillin, they are colocalized on the spindle structure during metaphases I and II. Phospho-PAK4 is distributed beneath the cytoplasmic membrane and on the chromosomes, and colocalized with the microtubule organizing center (MTOC) proteins, Pericentrin and γ-tubulin, as well as phosphor-MEK1/2 and phosphor-Paxillin on spindle poles. PAK4 inhibition by chemical inhibitor LCH-7749944, specific Pak4 morpholino oligo or the dominant negative mutant Pak4 K350, 351 M influence the meiotic resumption, spindle assembly and its cortical migration, and associated with the downregulation in the dephosphorylation of cyclin dependent kinase 1 (CDK1) and the levels of Cyclin B1, MEK1/2, Paxillin, g-tubulin, acetylated a-tubulin, Arp3, and Cofilin phosphorylation in oocytes. In sum, PAK4 functions to sustain the rational levels of Cyclin B1, MEK1/2, Paxillin, y-tubulin, acetylated a-tubulin, Arp3, and phosphor-Cofilin in mouse oocytes, thereby promotes the meiotic resumption, spindle assembly, and migration during meiotic maturation., (© 2024 Wiley‐VCH GmbH.)

Recent advances in targeted protein degradation (TPD) have propelled it to the forefront of small molecular drug discovery. Among these, hydrophobic tagging (HyT) strategies have garnered significant interest. Carbon-based hydrophobic tags have been recognized as effective Hyts for degrading a variety of target proteins. In this study, we introduce a novel class of potential EGFR degraders for the first time, which combine Gefitinib with silicon-based hydrophobic tags (SiHyT). The most promising candidate, degrader 7 , which links Gefitinib to a simple TBDPS silyl ether, has shown efficacy in degrading mutant EGFRs via the ubiquitin-proteosome system (UPS) both in vitro and in vivo. Notably, degrader 7 exhibits enhanced oral bioavailability owing to its superior metabolic stability compared to traditional carbon-based Hyts. Mechanistically, it was revealed that degrader 7 disrupts EGFR stability by dissociating the EGFR-HSP90 complex and recruiting E3 ligase, RNF149. More importantly, the potent and selective PD-L1 and BTK degraders were discovered successfully by utilizing the SiHyT strategy. The development of these innovative SiHyT compounds could broaden the repertoire of HyTs, enhancing the future design of TPD agents.

The establishment of epiblast-derived pluripotent stem cells (PSCs) from cattle, which are important domestic animals that provide humans with milk and meat while also serving as bioreactors for producing valuable proteins, poses a challenge due to the unclear molecular signaling required for embryonic epiblast development and maintenance of PSC self-renewal. Here, we selected six key stages of bovine embryo development (E5, E6, E7, E10, E12, and E14) to track changes in pluripotency and the dependence on signaling pathways via modified single-cell transcription sequencing technology. The remarkable similarity of the gene expression patterns between cattle and pigs during embryonic lineage development contributed to the successful establishment of bovine epiblast stem cells (bEpiSCs) using 3i/LAF (WNTi, GSK3βi, SRCi, LIF, Activin A, and FGF2) culture system. The generated bEpiSCs exhibited consistent expression patterns of formative epiblast pluripotency genes and maintained clonal morphology, normal karyotypes, and proliferative capacity for more than 112 passages. Moreover, these cells exhibited high-efficiency teratoma formation as well as the ability to differentiate into various cell lineages. The potential of bEpiSCs for myogenic differentiation, primordial germ cell like cells (PGCLCs) induction, and as donor cells for cell nuclear transfer was also assessed, indicating their promise in advancing cell-cultured meat production, gene editing, and animal breeding., (© 2024. The Author(s).)

Meniscus injuries present significant therapeutic challenges due to their limited self-healing capacity and diverse biological and mechanical properties across meniscal tissue. Conventional repair strategies neglect to replicate the complex zonal characteristics within the meniscus, resulting in suboptimal outcomes. In this study, we introduce an innovative, age- and stiffness-tunable meniscus decellularized extracellular matrix (DEM)-based hydrogel system designed for precision repair of heterogeneous, zonal-dependent meniscus injuries. By synthesizing age-dependent DEM hydrogels, we identified distinct cellular responses: fetal bovine meniscus-derived DEM promoted chondrogenic differentiation, while adult meniscus-derived DEM supported fibrochondrogenic phenotypes. The incorporation of methacrylate hyaluronic acid (MeHA) further refined the mechanical properties and injectability of the DEM-based hydrogels. The combination of age-dependent DEM with MeHA allowed for precise stiffness tuning, influencing cell differentiation and closely mimicking native tissue environments. In vivo tests confirmed the biocompatibility of hydrogels and their integration with native meniscus tissues. Furthermore, advanced 3D bioprinting techniques enabled the fabrication of hybrid hydrogels with biomaterial and mechanical gradients, effectively emulating the zonal properties of meniscus tissue and enhancing cell integration. This study represents a significant advancement in meniscus tissue engineering, providing a promising platform for customized regenerative therapies across a range of heterogeneous fibrous connective tissues., Competing Interests: Competing interests The authors declare no competing interests.

Cancer stem cells (CSCs) play a pivotal role in tumor initiation, proliferation, metastasis, drug resistance, and recurrence. Consequently, targeting CSCs has emerged as a promising avenue for cancer therapy. Recently, 3-phosphoglycerate dehydrogenase (PHGDH) has been identified as being intricately associated with the regulation of numerous cancer stem cells. Yet, reports detailing the functional regulators of PHGDH that can mitigate the stemness across cancer types are limited. In this study, the novel "molecular glue" LXH-3-71 was identified, and it robustly induced degradation of PHGDH, thereby modulating the stemness of colorectal cancer cells (CRCs) both in vitro and in vivo . Remarkably, LXH-3-71 was observed to form a dynamic chimera, between PHGDH and the DDB1-CRL E3 ligase. These insights not only elucidate the anti-CSCs mechanism of the lead compound but also suggest that degradation of PHGDH may be a more viable therapeutic strategy than the development of PHGDH inhibitors. Additionally, compound LXH-3-71 was leveraged as a novel ligand for the DDB1-CRL E3 ligase, facilitating the development of new PROTAC molecules targeting EGFR and CDK4 degradation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Accumulating oxidative damage is a primary driver of ovarian reserve decline along with aging. However, the mechanism behind the imbalance in reactive oxygen species (ROS) is not yet fully understood. Here we investigated changes in iron metabolism and its relationship with ROS disorder in aging ovaries of mice. We found increased iron content in aging ovaries and oocytes, along with abnormal expression of iron metabolic proteins, including heme oxygenase 1 (HO-1), ferritin heavy chain (FTH), ferritin light chain (FTL), mitochondrial ferritin (FTMT), divalent metal transporter 1 (DMT1), ferroportin1(FPN1), iron regulatory proteins (IRP1 and IRP2) and transferrin receptor 1 (TFR1). Notably, aging oocytes exhibited enhanced ferritinophagy and mitophagy, and consistently, there was an increase in cytosolic Fe2+, elevated lipid peroxidation, mitochondrial dysfunction, and augmented lysosome activity. Additionally, the ovarian expression of p53, p21, p16 and microtubule-associated protein tau (Tau) were also found to be upregulated. These alterations could be phenocopied with in vitro Fe2+ administration in oocytes from 2-month-old mice but were alleviated by deferoxamine (DFO). In vivo application of DFO improved ovarian iron metabolism and redox status in 12-month-old mice, and corrected the alterations in cytosolic Fe 2+ , ferritinophagy and mitophagy, as well as related degenerative changes in oocytes. Thereby in the whole, DFO delayed the decline in ovarian reserve and significantly increased the number of superovulated oocytes with reduced fragmentation and aneuploidy. Together, our findings suggest that aging-related disturbance in ovarian iron homeostasis contributes to excessive ROS production and that iron chelation may improve ovarian redox status, and efficiently delay the decline in ovarian reserve and oocyte quality in aging mice. These data propose a novel intervention strategy for preserving the ovarian reserve function in elderly women., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

PLD1 has been implicated in cytoskeletal reorganization and vesicle trafficking in somatic cells; however, its function remains unclear in oocyte meiosis. Herein, we found PLD1 stably expresses in mouse oocytes meiosis, with direct interaction with spindle, RAB11A + vesicles and macroautophagic/autophagic vacuoles. The genetic or chemical inhibition of PLD1 disturbed MTOC clustering, spindle assembly and its cortical migration, also decreased PtdIns(4,5)P 2 , phosphorylated CFL1 (p-CFL1 [Ser3]) and ACTR2, and their local distribution on MTOC, spindle and vesicles. Furthermore in PLD1-suppressed oocytes, vesicle size was significantly reduced while F-actin density was dramatically increased in the cytoplasm, the asymmetric distribution of autophagic vacuoles was broken and the whole autophagic process was substantially enhanced, as illustrated with characteristic changes in autophagosomes, autolysosome formation and levels of ATG5, BECN1, LC3-II, SQSTM1 and UB. Exogenous administration of PtdIns(4,5)P 2 or overexpression of CFL1 hyperphosphorylation mutant (CFL1 S3E ) could significantly improve polar MTOC focusing and spindle structure in PLD1-depleted oocytes, whereas overexpression of ACTR2 could rescue not only MTOC clustering, and spindle assembly but also its asymmetric positioning. Interestingly, autophagy activation induced similar defects in spindle structure and positioning; instead, its inhibition alleviated the alterations in PLD1-depleted oocytes, and this was highly attributed to the restored levels of PtdIns(4,5)P 2 , ACTR2 and p-CFL1 (Ser3). Together, PLD1 promotes spindle assembly and migration in oocyte meiosis, by maintaining rational levels of ACTR2, PtdIns(4,5)P 2 and p-CFL1 (Ser3) in a manner of modulating autophagy flux. This study for the first time introduces a unique perspective on autophagic activity and function in oocyte meiotic development. Abbreviations : ACTR2/ARP2: actin related protein 2; ACTR3/ARP3: actin related protein 3; ATG5: autophagy related 5; Baf-A1: bafilomycin A 1 ; BFA: brefeldin A; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GOLGA2/GM130: golgin A2; GV: germinal vesicle; GVBD: germinal vesicle breakdown; IVM: in vitro maturation; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MI: metaphase of meiosis I; MII: metaphase of meiosis II; MO: morpholino; MTOC: microtubule-organizing center; MTOR: mechanistic target of rapamycin kinase; PB1: first polar body; PLA: proximity ligation assay; PLD1: phospholipase D1; PtdIns(4,5)P 2 /PIP2: phosphatidylinositol 4,5-bisphosphate; RAB11A: RAB11A, member RAS oncogene family; RPS6KB1/S6K1: ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TUBA/α-tubulin: tubulin alpha; TUBG/γ-tubulin: tubulin gamma; UB: ubiquitin; WASL/N-WASP: WASP like actin nucleation promoting factor.

This study investigates viscoelastic guided wave properties (e.g., complex-wavenumber-, phase-velocity-, and attenuation-frequency relations) for multiple modes, including different orders of antisymmetric, symmetric, and shear horizontal modes in viscoelastic anisotropic laminated composites. To obtain those frequency-dependent relations, a guided wave characteristic equation is formulated based on a Legendre orthogonal polynomials expansion (LOPE)-assisted viscoelastodynamic model, which fuses the hysteretic viscoelastic model-based wave dynamics and the LOPE-based mode shape approximation. Then, the complex-wavenumber-frequency solutions are obtained by solving the characteristic equation using an improved root-finding algorithm, which leverages coefficient matrix determinant ratios and our proposed local tracking windows. To trace the solutions on the dispersion curves of different wave modes and avoid curve-tracing misalignment in regions with phase-velocity curve crossing, we presented a curve-tracing strategy considering wave attenuation. With the LOPE-assisted viscoelastodynamic model, the effects of material viscosity and fiber orientation on different guided wave modes are investigated for unidirectional carbon-fiber-reinforced composites. The results show that the viscosity in the hysteresis model mainly affects the frequency-dependent attenuation of viscoelastic guided waves, while the fiber orientation influences both the phase-velocity and attenuation curves. We expect the theoretical work in this study to facilitate the development of guided wave-based techniques for the NDT and SHM of viscoelastic anisotropic laminated composites.

Outbreaks of acute respiratory viral diseases, such as influenza and COVID-19 caused by influenza A virus (IAV) and SARS-CoV-2, pose a serious threat to global public health, economic security, and social stability. This calls for the development of broad-spectrum antivirals to prevent or treat infection or co-infection of IAV and SARS-CoV-2. Hemagglutinin (HA) on IAV and spike (S) protein on SARS-CoV-2, which contain various types of glycans, play crucial roles in mediating viral entry into host cells. Therefore, they are key targets for the development of carbohydrate-binding protein-based antivirals. This study demonstrated that griffithsin (GRFT) and the GRFT-based bivalent entry inhibitor GL25E (GRFT-L25-EK1) showed broad-spectrum antiviral effects against IAV infection in vitro by binding to HA in a carbohydrate-dependent manner and effectively protected mice from lethal IAV infection. Although both GRFT and GL25E could inhibit infection of SARS-CoV-2 Omicron variants, GL25E proved to be significantly more effective than GRFT and EK1 alone. Furthermore, GL25E effectively inhibited in vitro co-infection of IAV and SARS-CoV-2 and demonstrated good druggability, including favorable safety and stability profiles. These findings suggest that GL25E is a promising candidate for further development as a broad-spectrum antiviral drug for the prevention and treatment of infection or co-infection from IAV and SARS-CoV-2.IMPORTANCEInfluenza and COVID-19 are highly contagious respiratory illnesses caused by the influenza A virus (IAV) and SARS-CoV-2, respectively. IAV and SARS-CoV-2 co-infection exacerbates damage to lung tissue and leads to more severe clinical symptoms, thus calling for the development of broad-spectrum antivirals for combating IAV and SARS-CoV-2 infection or co-infection. Here we found that griffithsin (GRFT), a carbohydrate-binding protein, and GL25E, a recombinant protein consisting of GRFT, a 25 amino acid linker, and EK1, a broad-spectrum coronavirus inhibitor, could effectively inhibit IAV and SARS-CoV-2 infection and co-infection by targeting glycans on HA of IAV and spike (S) protein of SARS-CoV-2. GL25E is more effective than GRFT because GL25E can also interact with the HR1 domain in SARS-CoV-2 S protein. Furthermore, GL25E possesses favorable safety and stability profiles, suggesting that it is a promising candidate for development as a drug to prevent and treat IAV and SARS-CoV-2 infection or co-infection., Competing Interests: L.L., S.J., N.C., X.W., and Y.C. are the inventors in the patent or patent application covering the recombinant proteins GRFT and GL25E. Other authors declare no conflict of interest.

Facial editing is to manipulate the facial attributes of a given face image. Nowadays, with the development of generative models, users can easily generate 2D and 3D facial images with high fidelity and 3D-aware consistency. However, existing works are incapable of delivering a continuous and fine-grained editing mode (e.g., editing a slightly smiling face to a big laughing one) with natural interactions with users. In this work, we propose Talk-to-Edit, an interactive facial editing framework that performs fine-grained attribute manipulation through dialog between the user and the system. Our key insight is to model a continual "semantic field" in the GAN latent space. 1) Unlike previous works that regard the editing as traversing straight lines in the latent space, here the fine-grained editing is formulated as finding a curving trajectory that respects fine-grained attribute landscape on the semantic field. 2) The curvature at each step is location-specific and determined by the input image as well as the users' language requests. 3) To engage the users in a meaningful dialog, our system generates language feedback by considering both the user request and the current state of the semantic field. We demonstrate the effectiveness of our proposed framework on both 2D and 3D-aware generative models. We term the semantic field for the 3D-aware models as "tri-plane" flow, as it corresponds to the changes not only in the color space but also in the density space. We also contribute CelebA-Dialog, a visual-language facial editing dataset to facilitate large-scale study. Specifically, each image has manually annotated fine-grained attribute annotations as well as template-based textual descriptions in natural language. Extensive quantitative and qualitative experiments demonstrate the superiority of our framework in terms of 1) the smoothness of fine-grained editing, 2) the identity/attribute preservation, and 3) the visual photorealism and dialog fluency. Notably, the user study validates that our overall system is consistently favored by around 80% of the participants.

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is an immune checkpoint molecule with sequence homology to programmed cell death ligand 1 (PD-L1), which is mainly expressed on macrophages and tumor cells. However, whether Siglec-15-induced immunosuppression and poor prognosis are independent of PD-L1 remains unclear. In this study, we collected samples of 135 non-small cell lung cancers and found that Siglec-15 and PD-L1 expression were independent in non-small cell lung cancer by multiple immunofluorescence staining. Siglec-15 on macrophages (Mφ-Siglec-15) was significantly associated with DFS (p < 0.05) in PD-L1 - patients with non-metastasis lung adenocarcinoma, not in PD-L1 + or lung squamous cell carcinoma patients. Moreover, stromal Siglec-15 + macrophages of Mφ-Siglec-15 + PD-L1 - patients were significantly more than those of Mφ-Siglec-15 - PD-L1 - patients (p = 0.002). We further found that Siglec-15 + macrophages polarized toward M2 and produced more IL-10, negatively associated with inflamed immunophenotype in PD-L1 - patients and may inhibit CD8 + T cells infiltration. In conclusion, PD-L1-independent Siglec-15 + macrophages contribute to the formation of an immunosuppressive microenvironment in non-metastasis lung adenocarcinoma patients, which may cause a higher risk of recurrence. Siglec-15 could be a potential target for normalizing cancer immunotherapy, benefiting patients who fail to respond to anti-PD-L1 therapy., (© 2023. The Author(s).)

Covalent organic framework (COF) membranes featuring uniform topological structures and devisable functions, show huge potential in water purification and molecular separation. Nevertheless, the inability of uniform COF membranes to be produced on an industrial scale and their nonenvironmentally friendly fabrication method are the bottleneck preventing their industrial applications. Herein, we report a new green and industrially adaptable scraping-assisted interfacial polymerization (SAIP) technique to fabricate scalable and uniform TpPa COF membranes. The process used non-toxic and low-volatility ionic liquids (ILs) as organic phase instead of conventional organic solvents for interfacial synthesis of TpPa COF layer on a support membrane, which can simultaneously achieve the purposes of (i) improving the greenness of membrane-forming process and (ii) fabricating a robust membrane that can function beyond the conventional membranes. This approach yields a large-area, continuous COF membrane (19×25 cm 2 ) with a thickness of 78 nm within a brief period of 2 minutes. The resulting membrane exhibited an unprecedented combination of high permeance (48.09 L m -2 h -1 bar -1 ) and antibiotic desalination efficiency (e.g., NaCl/adriamycin separation factor of 41.8), which is superior to the commercial benchmarking membranes., (© 2023 Wiley-VCH GmbH.)

Background: Recent outbreaks of avian influenza and ongoing virus reassortment have drawn focus on spill-over infections. The increase in human infections with highly pathogenic avian influenza H5N6 virus and its high fatality rate posed a potential threat, necessitating the search for a more effective treatment., Methods: Longitudinal clinical data and specimens were collected from five H5N6 patients after admission. All patients received antiviral treatment of either sequential monotherapy of oseltamivir and baloxavir or the two drugs in combination. Severity of illness; viral load in sputum, urine, and blood; and cytokine levels in serum and sputum were serially analyzed., Findings: All patients developed acute respiratory distress syndrome (ARDS) and viral sepsis within 1 week after disease onset. When delayed oseltamivir showed poor effects, baloxavir was administered and rapidly decreased viral load. In addition, levels of IL-18, M-CSF, IL-6, and HGF in sputum and Mig and IL-18 in serum that reflected ARDS and sepsis deterioration, respectively, were also reduced with baloxavir usage. However, three patients eventually died from exacerbation of underlying disease and secondary bacterial infection. Nonsurvivors had more severe extrapulmonary organ dysfunction and insufficient H5N6 virus-specific antibody response., Conclusions: For critical human cases of H5N6 infection, baloxavir demonstrated effects on viral load and pulmonary/extrapulmonary cytokines, even though treatment was delayed. Baloxavir could be regarded as a first-line treatment to limit continued viral propagation, with potential future application in avian influenza human infections and poultry workers exhibiting influenza-like illness., Funding: This work was funded by the National Natural Science Foundation of China (81761128014)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Triple combination conversion therapy, involving transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), has shown an encouraging objective response rate (ORR) and successful conversion surgery rate in initially unresectable hepatocellular carcinoma (HCC). However, the safety and long-term survival outcomes of subsequent liver resection after successful conversion still remain to be validated. From February 2019 to February 2023, 726 patients were enrolled in this retrospective study (75 patients received hepatectomy after conversion therapy [CLR group], and 651 patients underwent pure hepatectomy [LR group]). Propensity score matching (PSM) was used to balance the preoperative baseline characteristics. After PSM, 68 patients in the CLR group and 124 patients in the LR group were analyzed, and all the matching variables were well-balanced. Compared with the LR group, the CLR group experienced longer Pringle maneuver time, longer operation time, and longer hospital stays. In addition, the CLR group had significantly higher incidence rates of intra-abdominal bleeding, biliary leakage, post-hepatectomy liver failure (PHLF), and Clavien-Dindo grade IIIa complications than the LR group. There were no significant statistical differences in overall survival (OS) (hazard ratio [HR] 0.724; 95% confidence interval [CI] 0.356-1.474; p = 0.374) and recurrence-free survival (RFS) (HR 1.249; 95% CI 0.807-1.934; p = 0.374) between the two groups. Liver resection following triple combination conversion therapy in initially unresectable HCC may achieve favorable survival outcomes with manageable safety profiles; presenting as a promising treatment option for initially unresectable HCC.

Continuous emergence of the Omicron variant, along with its subvariants, has caused an increasing number of infections, reinfections, and vaccine-breakthrough infections, seriously threatening human health. Recently, several new Omicron subvariants, such as BA.5, BA.2.75, BA.4.6, and BF.7, bearing distinct mutation profiles in their spike (S) proteins, have significantly increased their capacity to evade vaccine-induced immunity and have shown enhanced infectivity and transmissibility, quickly becoming dominant sublineages. In this study, we found the S proteins of these Omicron subvariants to have 2- to 4-fold more efficient membrane fusion kinetics than that of the original Omicron variant (BA.1), indicating that these novel Omicron subvariants might possess increased pathogenicity. We also identified that peptide-based pan-CoV fusion inhibitors, EK1 and EK1C4, showed equal efficacy against membrane fusion mediated by S proteins of the noted Omicron subvariants and infection by their pseudoviruses. Additionally, either immune sera induced by wild-type (WT) SARS-CoV-2 RBD-based vaccine or BA.2 convalescent sera showed potent synergism with EK1 against both WT SARS-CoV-2 and various Omicron subvariants, further suggesting that EK1-based fusion inhibitors are promising candidates for development as clinical antiviral agents against the currently circulating Omicron subvariants.

High-mobility group box 1 (HMGB1) can enhance the stability and accessibility of nucleus binding sites to nucleosomes and transcription factors. Recently, HMGB1 has been recognized as a positive regulator of tumor glutamine, and its overexpression has been correlated with tumorigenesis and cancer progression. However, functions and mechanisms of HMGB1 in regulation of glycolysis during cancer progression in lung adenocarcinoma (LUAD) is still unclear. Here, we found that intracellular HMGB1 was consistently upregulated in LUAD specimens, and positively relevant to tumor grade and poor survival. HMGB1 facilitated glycolysis and promoted metastasis through physical interaction with SET and HAT1, forming HMGB1/SET/HAT1 complex that inhibited H3K9 and H3K27 acetylation in LUAD. The functional proteins complex coordinated histone modification to suppress the expression of SASH1, thus further facilitating glycolysis and inducing the metastasis in vitro and in vivo. Consistent with this, the expression of SASH1 was negatively correlated with HMGB1, SET and GLUT1, and positively correlated with HAT1 in human LUAD specimens. Clinically, LUAD patients with high expression of HMGB1 and low expression of SASH1 exhibited the worst clinical outcomes. Overall, the findings of this study revealed the critical role of HMGB1 in glycolysis and metastasis by attenuating H3K9ace and H3K27ace through physical interacted with SET and HAT1, which may facilitate future targeted therapies., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Color-leaved O. fragrans is a variety of Osmanthus fragrans, which has both the fragrance of Osmanthus and the color of color-leaved plants. However, the molecular mechanism of color change of color-leaved O. fragrans is not clear. In this study, we analyzed the regulatory mechanism of four different color leaves of 'Ziyan Gongzhu' through physiological, transcriptome and metabolome levels., Results: Firstly, we measured the leaf pigments content and leaf chromatic parameters for correlation analysis, indicating a significant correlation between them. Overall, the content of chlorophyll a + b is low and the content of anthocyanin is high in T1 and T2 leaves, along with low expression of chlorophyll synthesis genes (HEMA, CHLG, and CAO, etc.) and high expression of anthocyanin synthesis genes (F3H, F3'H, DFR and ANS, etc.), resulting purple red and light purple in T1 and T2 leaves, respectively. It was also found that the pigment closely related to the color leaves of 'Ziyan Gongzhu' was cyanidin. The content anthocyanins, may be regulated by two putative MYB activators (OfMYB3 and OfMYB4) and two putative MYB repressors (OfMYB1 and OfMYB2). In contrast, the content of chlorophyll a + b is high and the content of anthocyanin is low in T3 and T4 leaves, along with high expression of chlorophyll synthesis genes and low expression of anthocyanin synthesis genes, resulting yellow green and dark green in T3 and T4 leaves, respectively. And abnormal chloroplast development affects chlorophyll content in T1, T2, and T3 leaves. Although the content of carotenoids first dropped in T2 leaves, it then rapidly accumulated in T4 leaves, in sync with the increase in the expression of genes related to carotenoid biosynthesis (ZDS, LHYB, and ZEP, for example). Analysis of photosynthetic, carbohydrate and hormone-related differentially abundant metabolites (DAMs) and DEGs found that they may participate in the regulation of leaf color change of 'Ziyan Gongzhu' by affecting pigment synthesis., Conclusion: Our results pave the way for a comprehensive knowledge of the regulatory processes governing leaf color in 'Ziyan Gongzhu' and identify possible genes for application regarding molecular colored-leaf cultivar breeding., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) has emerged as a novel immunotherapy candidate, which deserves a comprehensive investigation in lung adenocarcinoma (LUAD)., Methods: Multiplex fluorescence-based immunohistochemistry was conducted to assess Siglec-15 expression and tumor-infiltrating immune cells in LUAD from Tianjin cohort, with validation cohorts Xinchao 04 and 07., Results: This study revealed that Siglec-15 was positively correlated with CD8 + T cells and tumor-associated macrophages (TAMs) infiltration, but CD8 + T cells were mostly infiltrated in the stroma area, not in the tumor area. Spatially, fewer CD8 + T cells surrounded Siglec-15 + tumor cells in PD-L1 - cells, and more TAMs surrounded Siglec-15 + tumor cells in PD-L1 -/+ cells. Siglec-15 + TAMs infiltrated with more CD8 + T cells, and were closer to CD8 + T cells than Siglec-15 - TAMs and Siglec-15 + tumor cells. Siglec-15 + TAMs infiltrated with more Tregs and were closer to Tregs than Siglec-15 + tumor cells. Siglec-15 + tumor cells or TAMs reversed CD8 + T cells prognosis value, and enhanced the prognosis value of Tregs and TAMs. The immunotyping based on Siglec-15 and CD8A / CD8 + T cells revealed that patients with high CD8A and Siglec-15 expression exhibited immune activation. Patients with low CD8A expression / CD8 + T cells infiltration and Siglec-15 overexpression were related to the activation of immunosuppressive signature and metabolism-related pathway, and infiltrated with more TAMs., Conclusions: We revealed the distinct characteristics between Siglec-15 + tumor cells and TAMs in relation to CD8 + T cells, and a unique relationship between Siglec-15 and immunosuppressive TIME in LUAD, which may provide potential value for anti-Siglec-15 therapy., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The peptide-based pan-coronavirus fusion inhibitor EK1 is in phase III clinical trials, and it has, thus far, shown good clinical application prospects against SARS-CoV-2 and its variants. To further improve its in vivo long-acting property, we herein developed an Fc-binding strategy by conjugating EK1 with human immunoglobulin G Fc-binding peptide (IBP), which can exploit the long half-life advantage of IgG in vivo. The newly engineered peptide IBP-EK1 showed potent and broad-spectrum inhibitory activity against SARS-CoV-2 and its variants, including various Omicron sublineages and other human coronaviruses (HCoVs) with low cytotoxicity. In mouse models, IBP-EK1 possessed potent prophylactic and therapeutic efficacy against lethal HCoV-OC43 challenge, and it showed good safety profile and low immunogenicity. More importantly, IBP-EK1 exhibited a significantly extended in vivo half-life in rhesus monkeys of up to 37.7 h, which is about 20-fold longer than that reported for EK1. Strikingly, IBP-EK1 displayed strong in vitro or ex vivo synergistic anti-HCoV effect when combined with monoclonal neutralizing antibodies, including REGN10933 or S309, suggesting that IBP-conjugated EK1 can be further developed as a long-acting, broad-spectrum anti-HCoV agent, either alone or in combination with neutralizing antibodies, to combat the current COVID-19 pandemic or future outbreaks caused by emerging and re-emerging highly pathogenic HCoVs.

Tyrosine kinase inhibitors represented by sorafenib are the first-line treatment for hepatocellular carcinoma (HCC), but the low response rate of HCC patient has become a clinical pain-point. Emerging evidences have revealed that metabolic reprogramming plays an important role in regulating the sensitivity of tumor cells to various chemotherapeutics including sorafenib. However, the underlying mechanisms are very complex and are not fully elucidated. By comparing the transcriptome sequencing data of sorafenib-sensitive and -insensitive HCC patients, it is revealed that cofilin 1 (CFL1) is highly expressed in the tumor tissues of sorafenib-insensitive HCC patients and closely correlated with their poor prognosis. Mechanically, CFL1 can promote phosphoglycerate dehydrogenase transcription and enhance serine synthesis and metabolism to accelerate the production of antioxidants for scavenging the excessive reactive oxygen species induced by sorafenib, thereby impairing the sorafenib sensitivity of HCC. To translate this finding and consider the severe side effects of sorafenib, a reduction-responsive nanoplatform for systemic co-delivery of CFL1 siRNA (siCFL1) and sorafenib is further developed, and its high efficacy in inhibiting HCC tumor growth without apparent toxicity is demonstrated. These results indicate that nanoparticles-mediated co-delivery of siCFL1 and sorafenib can be a new strategy for the treatment of advanced HCC., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: The combination of sorafenib and hepatic arterial infusion chemotherapy (HAIC) is expected to exert a synergistic anticancer effect. We conducted this systematic review to examine the efficacy and safety of sorafenib plus HAIC vs sorafenib alone for advanced hepatocellular carcinoma (HCC)., Methods: We systematically searched the PubMed, Embase, and Cochrane Library with the following search terms: "sorafenib," "hepatic arterial infusion chemotherapy," "HAIC," "advanced," "hepatocellular carcinoma," and "HCC." Pooled hazard ratios (HRs) and 95% CIs were calculated for overall survival (OS) and progression-free survival (PFS), and we calculated the pooled risk ratios (RRs) and 95% CIs for objective response rate (ORR) and adverse events (AEs)., Results: We found that sorafenib plus HAIC was associated with significantly better OS (HR, 0.56; 95% CI, 0.37-0.83; P < 0.01), PFS (HR, 0.44; 95% CI, 0.27-0.72; P < 0.01), and ORR (RR, 3.77; 95% CI, 1.87-7.58; P < 0.01) than sorafenib alone in advanced HCC. Grade 3/4 AEs were more frequent in the sorafenib plus HAIC group, including leukopenia (RR, 4.54; 95% CI, 1.77-11.64; P < 0.01), neutropenia (RR, 7.81; 95% CI, 3.36-18.16; P < 0.01), thrombocytopenia (RR, 2.97; 95% CI, 1.98-4.46; P < 0.01), anemia (RR, 2.24; 95% CI, 1.22-4.09; P < 0.01), anorexia (RR, 2.37; 95% CI, 1.07-5.27; P = 0.03), nausea (RR, 2.98; 95% CI, 1.19-7.42; P = 0.02), and vomiting (RR, 3.99; 95% CI, 1.14-14.01; P = 0.03)., Conclusion: Sorafenib plus HAIC improved OS, PFS, and ORR compared with sorafenib alone in advanced HCC, with acceptable safety profile., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

There is growing interest in the relationship between neighborhood social capital and the health of urban older people, but existing research still falls short in exploring the relationship between the two. Based on 2018 CHARLS data, this paper quantitatively examines the association between neighborhood social capital and the self-rated health of urban older people. The study found that, after controlling for a series of variables, both increased social interaction and increased frequency of social interaction significantly improved urban older people's self-rated health. To implement the Health China strategy and improve the health of urban older people, further attention should be paid to the role of neighborhood social capital, creating a harmonious environment for neighborhood interaction and promoting the cultivation of neighborhood social capital.

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E ( TBCE ) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Numerous emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants have shown significant immune evasion capacity and caused a large number of infections, as well as vaccine-breakthrough infections, especially in elderly populations. Recently emerged Omicron XBB was derived from the BA.2 lineage, but bears a distinct mutant profile in its spike (S) protein. In this study, we found that Omicron XBB S protein drove more efficient membrane-fusion kinetics on human lung-derived cells (Calu-3). Considering the high susceptibility of the elderly to the current Omicron pandemic, we performed a comprehensive neutralization assessment of elderly convalescent or vaccine sera against XBB infection. We found that the sera from elderly convalescent patients who experienced with BA.2 infection or breakthrough infection potently inhibited BA.2 infection, but showed significantly reduced efficacy against XBB. Moreover, recently emerged XBB.1.5 subvariant also showed more significant resistance to the convalescent sera of BA.2- or BA.5-infected elderly. On the other hand, we found that the pan-CoV fusion inhibitors EK1 and EK1C4 can potently block either XBB-S- or XBB.1.5-S-mediated fusion process and viral entry. Moreover, EK1 fusion inhibitor showed potent synergism when combined with convalescent sera of BA.2- or BA.5-infected patients against XBB and XBB.1.5 infection, further indicating that EK1-based pan-CoV fusion inhibitors are promising candidates for development as clinical antiviral agents to combat the Omicron XBB subvariants., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Although voice authentication is generally secure, voiceprint-based authentication methods have the drawback of being affected by environmental noise, long passphrases, and large registered samples. Therefore, we present a breakthrough idea for smartphone user authentication by analyzing articulation and integrating the physiology and behavior of the vocal tract, tongue position, and lip movement to expose the uniqueness of individuals while making utterances. The key idea is to leverage the smartphone speaker and microphone to simultaneously transmit and receive speech and ultrasonic signals, construct identity-related features, and determine whether a single utterance is a legitimate user or an attacker. Physiological authentication methods prevent other users from copying or reproducing passwords. Compared to other types of behavioral authentication, the system is more accurately able to recognize the user's identity and adapt accordingly to environmental variations. The proposed system requires a smaller number of samples because single utterances are utilized, resulting in a user-friendly system that resists mimicry attacks with an average accuracy of 99% and an equal error rate of 0.5% under the three different surroundings.

Angiogenesis inhibition has become a promising therapeutical strategy for cancer treatment. Current clinical anti-angiogenesis treatment includes antibodies against vascular endothelial growth factor (VEGF) or VEGF receptor, fusion proteins with high affinity to VEGF receptor, and tyrosine kinase inhibitors of VEGF receptor. However, current treatments are prone to systemic toxicity or acquiring drug resistance. A natural bioactive lipid 1,2-dipalmitoyl-sn‑glycero-3-phosphate (dipalmitoyl phosphatidic acid, DPPA) was reported to exhibit anti-angiogenic and anti-tumoral activity. However, the hydrophobic property of DPPA largely restricted its clinical use, while systemic infusion of free DPPA could result in undesirable side effects. Herein, we successfully developed DPPA-based lipid-nanoparticles (DPPA-LNPs) which turns the "therapeutic payload into nanocarrier". This strategy could improve on DPPA's hydrophiliciy, thereby facilitating its systemic administration. . DPPA-LNPs not only retained the therapeutic anti-angiogenic and anti-tumoral bioactivity of parental DPPA, but also greatly improved its tumor targeting ability via enhanced permeability and retention (EPR) effect. This strategy not only eliminates the limitation of drug encapsulation rate, toxicity of the delivery vehicle; but also enhances DPPA bioacvtity in vitro and in vivo. Systemic administration of DPPA-LNPs significantly suppressed the blood vessel formation and tumor growth of triple negative breast cancer and liver cancer growth on both xenograft tumor models. STATEMENT OF SIGNIFICANCE: This is the first-in-kind self-therapeutic inherent lipid to be made into a nanocarrier, with inherent anti-angiogenic and anti-tumor properties. DPPA nanocarrier is fully natural, fully compatible with minimal systemic toxicity. DPPA nanocarrier can accumulate at high concentration at tumor via EPR effect, exerting both anti-angiogenic and anti-tumor effects in vivo. DPPA nanocarrier could be used to encapsulate biologics or small molecules for synergistic anti-cancer therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Broussonetia papyrifera is rich in flavonoids, which have significant antioxidant, antibacterial, and anti-inflammatory activities and certain pharmacological activities. Nevertheless, scarce transcriptome resources of B. papyrifera have impeded further study regarding the process of its production and accumulation. In this study, RNA-seq was utilized to evaluate the gene expression of B. papyrifera leaves at three distinct developmental phases (T1: young leaves, T3: immature leaves, T4: matured leaves). We obtained 2447 upregulated and 2960 downregulated DEGs, 4657 upregulated and 4804 downregulated DEGs, and 805 upregulated and 484 downregulated DEGs from T1 vs. T3, T1 vs. T4, and T3 vs. T4, respectively. Further research found that the following variables contributed to the formation of flavonoids in the leaves of B. papyrifera : Several important enzyme genes involved in flavonoid production pathways have been discovered. The results demonstrated that the dynamic changing trend of flavonoid contents is related to the expression pattern of the vast majority of essential genes in the biosynthetic pathway. Genes associated in energy and glucose metabolism, polysaccharide, cell wall and cytoskeleton metabolism, signal transduction, and protein and amino acid metabolism may affect the growth and development of B. papyrifera leaves, and eventually their flavonoid content. This study's results offer a strong platform for future research into the metabolic pathways of B. papyrifera ., Competing Interests: The authors declare no conflict of interest.

Diabetes has been associated with postoperative complications, such as increased risk of tissue infection and impaired tissue repair caused by destabilization of hypoxia-inducible factor-1α (HIF-1α). Consequently, it is imperative to fabricate anti-bacterial and pro-regenerative small-diameter vascular grafts for treating cardiovascular disease in diabetic patients. Herein, we developed electrospun cobalt ion (Co 2+ )-loaded poly (ε-caprolactone) (PCL) microfiber vascular grafts (PCL-Co grafts). The released Co 2+ significantly increased the stabilization of HIF-1α in high-glucose (HG)-treated HUVECs (HG-HUVECs) and macrophages (HG-macrophages). This resulted in enhanced cell migration, nitric oxide production, and secretion of bioactive factors by HG-HUVECs, and polarization of HG-macrophages toward M2 phenotypes in vitro. The Co 2+ also conferred anti-bacterial properties to the grafts, while not perturbing the inherent anti-bacterial activities of HG-macrophages. Following abdominal artery implantation into type 2 diabetes mellitus (T2DM) rats, PCL-Co grafts were evaluated for performance in infection (grafts pre-contaminated with Staphylococcus aureus) and prophylaxes models (grafts alone). PCL-Co grafts prevented the incidence of subsequent infection in prophylaxes model and effectively inhibited the bacterial growth in the infection model. PCL-Co grafts also significantly enhanced cellularization, vascularization, endothelialization, contractile SMC regeneration and macrophages polarization in both models. Collectively, PCL-Co grafts exhibited the potential to combat infection and improve tissue regeneration under diabetes conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Nitric oxide (NO) plays various physiological and pathological roles in lots of biological processes. It is crucial to detect NO sensitively and selectively in vivo and in vitro as homeostasis of NO is closely related to various diseases. Herein, a novel dual-channel fluorescent dye (ENNH 2 ) based on dicarboxyimide anthracene was developed as a highly sensitive and selective probe to detect NO in living systems using the dual-channel fluorescence. ENNH 2 can emit bright red fluorescence due to the intramolecular charge transfer (ICT) from the amino group at the 6-position of 1,2-dicarboxyimide anthracene to the conjugated aromatic ring, and the ICT is effectively inhibited by the reductive deamination of the amino in the presence of NO to obtain the remarkable strong green emission with the excellent sensitivity (5.52 nM). Promisingly, ENNH 2 exhibits an excellent performance in endogenous NO dual-channel fluorescence imaging of RAW 264.7 cells and zebrafish., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Somatic copy number alterations (SCNA), which are widespread in cancer, can predict the efficacy of immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC). However, the usefulness of SCNA for predicting the survival of patients treated with cytokine-induced killer (CIK) cells or chemotherapy (CT) is unknown. This study aimed to explore the correlation between SCNA and clinical outcome in NSCLC patients treated with CIK + CT or CT alone. We performed whole-exome sequencing on 45 NSCLC patients treated with CIK + CT, as well as 305 NSCLC patients treated with CT alone, from The Cancer Genome Atlas, which showed SCNA had a superiority in predicting the progression-free survival (PFS) over tumor mutation burden (TMB) and SCNA + TMB in NSCLC patients treated with CIK + CT, especially in lung adenocarcinoma, while SCNA could not predict the efficacy of CT alone. Additionally, we investigated the association between SCNA and immune cell infiltration by RNA sequencing and immunohistochemistry. The results revealed that SCNA was negatively associated with the expression of dendritic cells. Collectively, this study revealed a negative correlation between SCNA and response to CIK + CT and showed that SCNA is a predictive indicator in LUAD patients treated with CIK + CT., (© 2022. The Author(s).)

Multi-modality magnetic resonance (MR) images provide complementary information for disease diagnoses. However, modality missing is quite usual in real-life clinical practice. Current methods usually employ convolution-based generative adversarial network (GAN) or its variants to synthesize the missing modality. With the development of vision transformer, we explore its application in the MRI modality synthesis task in this work. We propose a novel supervised deep learning method for synthesizing a missing modality, making use of a transformer-based encoder. Specifically, a model is trained for translating 2D MR images from T1-weighted to T2-weighted based on conditional GAN (cGAN). We replace the encoder with transformer and input adjacent slices to enrich spatial prior knowledge. Experimental results on a private dataset and a public dataset demonstrate that our proposed model outperforms state-of-the-art supervised methods for MR image synthesis, both quantitatively and qualitatively. Clinical relevance- This work proposes a method to synthesize T2-weighted images from T1-weighted ones to address the modality missing issue in MRI.

Background: To compare the early clinical outcomes and Magnetic Resonance Imaging (MRI) results of Delta Medical's PEEK (polyether ether ketone) suture anchor with those of Smith & Nephew's PEEK suture anchor in patients with arthroscopic rotator cuff repair., Methods: A total of 106 patients in four different medical centers were randomly allocated into two groups: Delta Medical's PEEK suture anchor (53 patients); Smith & Nephew's PEEK suture anchor (53 patients). The MRI results and early clinical outcomes were evaluated at 3 and 6 months postoperatively. The University of California at Los Angeles (UCLA) shoulder rating scale and the visual analog scale (VAS) score for pain and range of motion were evaluated. MRI were performed at 3 and 6 months postoperatively to examine the integrity of the repaired rotator cuff tendon based on the Sugaya classification., Results: Significant improvements in pain relief, shoulder function, and functional scores were observed in both groups after surgery regardless of the suture anchor applied (P<0.001). No differences observed in the functional scores and range of motion. The assessments of UCLA scores at 3 and 6 months produced no statistical differences (P=0.885 and 0.340, respectively). The mean VAS scores in group 1 did not reveal statistical differences at 3 and 6 months after surgery compared to group 2. No significant differences in the range of motion were found at each follow-up time-point and no shifting or breakage of the anchors occurred between the two groups (P>0.01). No major intra- or post-operative complications, such as infection, and vessel or nerve injury., Conclusions: Pain relief and shoulder function were improved after complete rotator cuff repair in both groups, regardless of the suture anchor applied. The difference in functional scores and range of motion were not significant in groups 1 and 2. Delta Medical's PEEK suture anchor had a non-inferiority effect compared to Smith & Nephew's PEEK suture anchor. Delta Medical's PEEK suture anchor was suitable for arthroscopic rotator cuff repair., Trial Registration: Chinese Clinical Trial Registry, identifier: ChiCTR2100051716., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-6008). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Digital twin (DT) and artificial intelligence (AI) technologies have grown rapidly in recent years and are considered by both academia and industry to be key enablers for Industry 4.0. As a digital replica of a physical entity, the basis of DT is the infrastructure and data, the core is the algorithm and model, and the application is the software and service. The grounding of DT and AI in industrial sectors is even more dependent on the systematic and in-depth integration of domain-specific expertise. This survey comprehensively reviews over 300 manuscripts on AI-driven DT technologies of Industry 4.0 used over the past five years and summarizes their general developments and the current state of AI-integration in the fields of smart manufacturing and advanced robotics. These cover conventional sophisticated metal machining and industrial automation as well as emerging techniques, such as 3D printing and human-robot interaction/cooperation. Furthermore, advantages of AI-driven DTs in the context of sustainable development are elaborated. Practical challenges and development prospects of AI-driven DTs are discussed with a respective focus on different levels. A route for AI-integration in multiscale/fidelity DTs with multiscale/fidelity data sources in Industry 4.0 is outlined.

Background: Lung adenocarcinoma (LUAD) contains a variety of genomic and epigenomic abnormalities; the effective tumor markers related to these abnormalities need to be further explored., Methods: Clustering analysis was performed based on DNA methylation (MET), DNA copy number variation (CNV), and mRNA expression data, and the differences in survival and tumor immune microenvironment (TIME) between subtypes were compared. Further, we evaluated the signatures in terms of both prognostic value and immunological characteristics., Results: There was a positive correlation between MET and CNV in LUAD. Integrative analysis of multi-omics data from 443 samples determined molecular subtypes, iC1 and iC2. The fractions of CD8+ T cells and activated CD4+ T cells were higher, the fraction of Tregs was lower, and the expression level of programmed death-ligand 1 (PD-L1) was higher in iC2 with a poor prognosis showing a higher TIDE score. We selected PTTG1 , SLC2A1 , and FAM83A as signatures of molecular subtypes to build a prognostic risk model and divided patients into high-risk group and low-risk group representing poor prognosis and good prognosis, respectively, which were validated in 180 patients with LUAD. Further, the low-risk group with lower TIDE score had more infiltrating immune cells. In 100 patients with LUAD, the high-risk group with an immunosuppressive state had a higher expression of PD-L1 and lower counts of CD8+ T cells and dendritic cells., Conclusions: These findings demonstrated that combined multi-omics data could determine molecular subtypes with significant differences of prognosis and TIME in LUAD and suggested potent utility of the signatures to guide immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Li, Guo, Wu, Kou and Yang.)

Objective: Lung cancer is the most common cause of cancer-related deaths worldwide. Somatic copy number alterations (SCNAs) have been used to predict responses to therapies in many cancers, including lung cancer. However, little is known about whether they are predictive of radiotherapy outcomes. We aimed to understand the prognostic value and biological functions of SCNAs., Methods: We analyzed the correlation between SCNAs and clinical outcomes in The Cancer Genome Atlas data for 486 patients with non-small cell lung cancer who received radiotherapy. Gene set enrichment analyses were performed to investigate the potential mechanisms underlying the roles of SCNAs in the radiotherapy response. Our results were validated in 20 patients with lung adenocarcinoma (LUAD) receiving radiotherapy., Results: SCNAs were a better predictor of progression-free survival (PFS) in LUAD ( P = 0.024) than in lung squamous carcinoma ( P = 0.18) in patients treated with radiotherapy. Univariate and multivariate regression analyses revealed the superiority of SCNAs in predicting PFS in patients with LUAD. Patients with stage I cancer and low SCNA levels had longer PFS than those with high SCNA levels ( P = 0.022). Our prognostic nomogram also showed that combining SCNAs and tumor/node/metastasis provided a better model for predicting long-term PFS. Additionally, high SCNA may activate the cell cycle pathway and induce tumorigenesis., Conclusions: SCNAs may be used to predict PFS in patients with early-stage LUAD with radiotherapy, in combination with TNM, with the aim of predicting long-term PFS. Therefore, SCNAs are a novel predictive biomarker for radiotherapy in patients with LUAD., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2021 Cancer Biology & Medicine.)

The classical factors for predicting prognosis currently cannot meet the developing requirements of individualized and accurate prognostic evaluation in lung adenocarcinoma (LUAD). With the rapid development of high-throughput DNA sequencing technologies, genomic changes have been discovered. These sequencing data provide unprecedented opportunities for identifying cancer molecular subtypes. In this article, we classified LUAD into two distinct molecular subtypes (Cluster 1 and Cluster 2) based on Copy Number Variations (CNVs) and mRNA expression data from the Cancer Genome Atlas (TCGA) based on non-negative matrix factorization. Patients in Cluster 1 had worse outcomes than that in Cluster 2. Molecular features in subtypes were assessed to explain this phenomenon by analyzing differential expression genes expression pattern, which involved in cellular processes and environmental information processing. Analysis of immune cell populations suggested different distributions of CD4+ T cells, CD8+ T cells, and dendritic cells in the two subtypes. Subsequently, two novel genes, TROAP and RASGRF1, were discovered to be prognostic biomarkers in TCGA, which were confirmed in GSE31210 and Tianjin Medical University Cancer Institute and Hospital LUAD cohorts. We further proved their crucial roles in cancers by vitro experiments. TROAP mediates tumor cell proliferation, cycle, invasion, and migration, not apoptosis. RASGRF1 has a significant effect on tumor microenvironment. In conclusion, our study provides a novel insight into molecular classification based on CNVs related genes in LUAD, which may contribute to identify new molecular subtypes and target genes., (Copyright © 2021. Published by Elsevier Inc.)

Mechanistic understanding of the topological cues delivered by biomaterials in promotion of oriented tissue regeneration (e.g., peripheral nerve regrowth) remains largely elusive. Here, we engineered nerve conduits composed of oriented microfiber-bundle cores and randomly organized nanofiber sheaths to particularly interrogate the regulatory mechanism of microfiber orientation on promoted peripheral nerve regeneration. With comprehensive yet systematic analyses, we were able to elucidate the intricate cascade of biological responses associated with conduit-assisted nerve regrowth, i.e., oriented microfibers facilitated macrophage recruitment and subsequent polarization toward a pro-healing phenotype, which in turn promoted Schwann cell (SC) migration, myelinization and axonal extension. Pronounced improvement of nerve regeneration in rat sciatic nerve injury was evidenced with enhanced electrophysiologic function, sciatic functional index and alleviated muscle atrophy 3 months post-implantation. The obtained results offer essential insights on the topological regulation of biomaterials in functional nerve tissue regeneration via immune modulation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cellular transition to hypoxia following tissue injury, has been shown to improve angiogenesis and regeneration in multiple tissues. To take advantage of this, many hypoxia-mimicking scaffolds have been prepared, yet the oxygen access state of implanted artificial small-diameter vascular grafts (SDVGs) has not been investigated. Therefore, the oxygen access state of electrospun PCL grafts implanted into rat abdominal arteries was assessed. The regions proximal to the lumen and abluminal surfaces of the graft walls were normoxic and only the interior of the graft walls was hypoxic. In light of this differential oxygen access state of the implanted grafts and the critical role of vascular regeneration on SDVG implantation success, we investigated whether modification of SDVGs with HIF-1α stabilizer dimethyloxalylglycine (DMOG) could achieve hypoxia-mimicking responses resulting in improving vascular regeneration throughout the entirety of the graft wall. Therefore, DMOG-loaded PCL grafts were fabricated by electrospinning, to support the sustained release of DMOG over two weeks. In vitro experiments indicated that DMOG-loaded PCL mats had significant biological advantages, including: promotion of human umbilical vein endothelial cells (HUVECs) proliferation, migration and production of pro-angiogenic factors; and the stimulation of M2 macrophage polarization, which in-turn promoted macrophage regulation of HUVECs migration and smooth muscle cells (SMCs) contractile phenotype. These beneficial effects were downstream of HIF-1α stabilization in HUVECs and macrophages in normoxic conditions. Our results indicated that DMOG-loaded PCL grafts improved endothelialization, contractile SMCs regeneration, vascularization and modulated the inflammatory reaction of grafts in abdominal artery replacement models, thus promoting vascular regeneration., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Catalpa bungei is an important resource of timber, belonging to the genus catalpa (Bignoniaceae). In this study, we sequenced complete chloroplast (cp) genome of C. bungei , using a NovaSeq 6000 sequencing platform. The genome of the C. bungei was 152,153 bp in length, including a large single-copy region (84,910 bp), a small single-copy region (12,664 bp), and two inverted repeats regions (30,285 bp). It encodes 126 genes, including 81 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analyses were performed based on 15 cp genomes using the maximum likelihood (ML) method, supported that C. bungei was probably more closely related to C . speciosa . This study, the cp genome of C. bungei was assembled, which will provide more theoretical basis for determine the phylogenetic relationships of the Catalpa and related species., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is considered a novel anti-tumor target comparable to programmed cell death 1 ligand 1(PD-L1). However, little is known about Siglec-15. Our study aims to understand its expression signature, prognosis value, immune infiltration pattern, and biological function using multi-omic bioinformatics from public databases and verify them in lung cancer patients. Integrated analysis of The Cancer Genome Atlas and Genotype-Tissue Expression portals showed Siglec-15 was overexpressed across cancers. Genetic and epigenetic alteration analysis was performed using cBioportal and UALCAN, showed Siglec-15 was regulated at the genetic and epigenetic levels. Survival estimated using Kaplan-Meier plotter indicated high Siglec-15 expression correlated with favorable or unfavorable outcomes depending on the different type and subtype of cancer. Components of immune microenvironment were analyzed using CIBERSORT, and the correlation between immune cells and Siglec-15 was found to be distinct across cancer types. Based on Gene Set Enrichment Analysis, Siglec-15 was implicated in pathways involved in immunity, metabolism, cancer, and infectious diseases. Lung cancer patients with positive Siglec-15 expression showed significantly short survival rates in progression-free survival concomitant with reduced infiltration of CD20 + B, and dendritic cells by immunohistochemistry. Quantitative real-time PCR results indicated the overexpression of Siglec-15 was correlated with activation of the chemokine signaling pathway. In conclusion, Siglec-15 could serve as a vital prognostic biomarker and play an immune-regulatory role in tumors. These results provide us with clues to better understand Siglec-15 from the perspective of bioinformatics and highlight the importance of Siglec-15 in many types of cancer., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Percutaneous coronary intervention for coronary artery disease treatment often results in pathological vascular injury, characterized by P-selectin overexpression. Adipose-derived stem cells (ADSCs) therapeutic efficacy remains elusive due to poor ADSCs targeting and retention in injured vessels. Here, conjugated P-selectin binding peptide (PBP) to polyethylene glycol-conjugated phospholipid derivative (DMPE-PEG) linkers (DMPE-PEG-PBP; DPP) are used to facilitate the modification of PBP onto ADSCs cell surfaces via hydrophobic interactions between DMPE-PEG and the phospholipid bilayer. DPP modification neither has influence on ADSCs proliferation nor apoptosis/paracrine factor gene expression. A total of 5 × 10 -6 m DPP-modified ADSCs (DPP-ADSCs) strongly binds to P-selectin-displaying activated platelets and endothelial cells (ECs) in vitro and to wire-injured rat femoral arteries when administered by intra-arterial injection. Targeted binding of ADSCs shields injury sites from platelet and leukocyte adhesion, thereby decreasing inflammation at injury sites. Furthermore, targeted binding of ADSCs recovers injured ECs functionality and reduces platelet-initiated vascular smooth muscle cells (VSMCs) chemotactic migration. Targeted binding of DPP-human ADSCs to balloon-injured human femoral arteries is also demonstrated in ex vivo experiments. Overall, DPP-ADSCs promote vascular repair, inhibit neointimal hyperplasia, increase endothelium functionality, and maintain normal VSMCs alignment, supporting preclinical noninvasive utilization of DPP-ADSCs for vascular injury., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Abstract Iron (Fe), which is a necessary micronutrient for algal growth, plays an important role in the physiological metabolism and enzymatic reactions of algae. This study aimed to investigate the absorption process of four kinds of complexing iron absorbed by Anabaena flos-aquae . Results showed that the absorptive capacity of A. flos-aquae to complex iron was inversely proportional to the stability of the complex bond of complex iron. Complex iron with weak binding ability can be quickly adsorbed by A. flos-aquae . The absorptive rate was as follows: ferric humate, ferric oxalate >ammonium ferric citrate >EDTA Fe. For EDTA-Fe with a strong binding ability, a moderate iron concentration (e.g. 0.6 mg l -1 ) is favourable for iron uptake by A. flos-aquae . Our experiments also revealed that the process of separating iron from complex iron before entering algal cells was probably as follows: iron complexed with organic ligands were firstly adsorbed on the surface of algae cells; afterwards, iron ions were captured by organic matter on the surface of algae cells, accompanied by the rupture of the bond between Fe 3+ and ligand; finally, the Fe 3+ entered into the cell of algae while the organic ligands returned to the medium.

Globally growing problems related to cardiovascular diseases lead to a considerable need for synthetic vascular grafts. For small-caliber vascular prosthesis, it remains essential to fulfill rapid endothelialization, inhibit intimal hyperplasia, and prevent calcification for keeping patency. To modulate vascular regeneration, herein, we developed a bioactive trilayered tissue-engineered vascular graft encapsulating both microRNA-126 and microRNA-145 in the fibrous inner and middle layers, respectively. In vitro cell activities demonstrated that the trilayered electrospun membranes had significant biological advantages in enhanced growth and intracellular nitric oxide production of vascular endothelial cells, modulation of phenotypes of vascular smooth muscle cells (SMCs), and restraint of calcium deposition through fast-releasing microRNA-126 and slow-releasing microRNA-145. Histological and immunofluorescent analyses of in vivo implantation in a rat abdominal aorta interposition model suggested that the dual-microRNA-loading trilayered electrospun graft exerted a positive effect on accelerating endothelialization, improving contractile SMC regeneration, and promoting normal extracellular matrix formation. Meanwhile, the local bioactivity of microRNA-126 and microRNA-145 in the trilayered vascular graft could regulate inflammation and depress calcification possibly by facilitating transformation of macrophages into the anti-inflammatory M2 phenotype. These findings indicated that the trilayered electrospun graft by local delivery of dual microRNAs could be possibly used as a bioactive substitute for replacement of artificial small-caliber blood vessels.