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Augmented reality (AR) technology can enhance picture book reading experience. The present study aimed to explore the influence of reading AR picture books on primary school students' reading comprehension, story retelling, and reading motivation. Eighty second graders, who were from two classes at a rural primary school in a coastal city in East China, were recruited through convenience sampling to participate in this quasi-experimental study. The two classes were randomly assigned to be either the experimental group (AR picture book reading) or control group (print picture book reading), and both groups read three traditional Chinese picture books during reading classes throughout three weeks. T-test analyses revealed that, before the study began, the two groups did not have significant differences in reading comprehension, story retelling, or reading motivation. However, after the three weeks of instructional intervention, the experimental group significantly outperformed the control group in all three aspects. Furthermore, MANCOVA analysis showed that reading AR picture books was more effective in boosting participants' performance on implicit questions during the reading comprehension tests. They also performed significantly higher on story retelling tests, especially when it came to story structures regarding settings and plots. In addition, AR picture book reading was more conducive to improving participants' level of attention and confidence in reading. This work adds to the ongoing endeavors in incorporating AR picture books into classroom settings, and will inform future development of original Chinese picture books with AR technology.

Abstract Background Human epithelium-derived stem cells and induced pluripotent stem cells (hiPSCs) possess the capability to support tooth formation and differentiate into functional enamel-secreting ameloblasts, making them promising epithelial-component substitutes for future human tooth regeneration. However, current tissue recombination approaches are not only technically challenging, requiring precise induction procedures and sophisticated microsurgery, but also exhibit low success rates in achieving tooth formation and ameloblastic differentiation. Methods Suspended human keratinocyte stem cells (hKSCs) or cells from three hiPSC lines were directly mixed with dissociated embryonic mouse dental mesenchymal cells (mDMCs) that possess odontogenic potential in different proportions and reaggregated them to construct bioengineered tooth germs. The success rates of tooth formation and ameloblastic differentiation were confirmed after subrenal culture. The sorting capability, sequential development, and ameloblastic differentiation of stem cells were examined via GFP tracing, RT-PCR, and histological analysis, respectively. Results Our reaggregation approach achieved an impressive success rate of more than 90% in tooth formation and 100% in ameloblastic differentiation when the chimeric tooth germs contained 1%~10% hKSCs or 5% hiPSCs. In addition, we observed that hiPSCs, upon exposure to mDMCs, initially transformed into epidermal cells, as indicated by KRT14 and CD29 expression, before progressing into dental epithelial cells, as indicated by SP6 and SHH expression. We also found that epithelial-derived hiPSCs, when reaggregated with mDMCs, were more favorable for tooth formation than their mesenchymal-derived counterparts. Conclusions This study establishes a simplified yet highly effective cell-cell reaggregation strategy for inducing stem cells to support tooth formation and differentiate into functional ameloblasts, paving the way for novel approaches for the development of stem cell-based tooth organoids and bioengineered tooth germs in vitro.

Due to overactive inflammation and hindered angiogenesis, self-healing of diabetic wounds (DW) remains challenging in the clinic. Platelet-derived exosomes (PLT-Exos), a novel exosome capable of anti-inflammation and pro-angiogenesis, show great potential in DW treatment. However, previous administration of exosomes into skin wounds is topical daub or intradermal injection, which cannot intradermally deliver PLT-Exos into the dermis layer, thus impeding its long-term efficacy in anti-inflammation and pro-angiogenesis. Herein, a dissolvable microneedle-based wound dressing (PLT-Exos@ADMMA-MN) was developed for transdermal and long-term delivery of PLT-Exos. Firstly, a photo-crosslinking methacrylated acellular dermal matrix-based hydrogel (ADMMA-GEL), showing physiochemical tailorability, fast-gelling performance, excellent biocompatibility, and pro-angiogenic capacities, was synthesized as a base material of our dressing. For endowing the dressing with anti-inflammation and pro-angiogenesis, PLT-Exos were encapsulated into ADMMA-GEL with a minimum effective concentration determined by our in-vitro experiments. Then, in-vitro results show that this dressing exhibits excellent properties in anti-inflammation and pro-angiogenesis. Lastly, in-vivo experiments showed that this dressing could continuously and transdermally deliver PLT-Exos into skin wounds to switch local macrophage into M2 phenotype while stimulating neovascularization, thus proving a low-inflammatory and pro-angiogenic microenvironment for DW healing. Collectively, this study provides a novel wound dressing capable of suppressing inflammation and stimulating vascularization for DW treatment.

Introduction The rapid growth of e-cigarette usage among youth and young people has emerged as a significant public health concern. It is imperative to initiate effective vaping prevention campaigns and undertake relevant research to address this pressing issue. This research seeks to identify effective video advertisements to deter young people from starting to use e-cigarettes. It aims to offer evidencebased insights and recommendations for creating communication materials and designing messages for youth e-cigarette prevention efforts. Methods College students aged 18–24 years (n=40) participated in focus groups within this qualitative study. After viewing four stimulus videos, participants discussed what they perceived as effective and ineffective video characteristics, as well as suggestions for future videos. Results Effective video characteristics included the use of real-life testimonials, displaying specific health hazards, revealing harmful chemical ingredients and the deceptive nature of flavors, and positively perceived effectiveness. Participants generally found that videos with strong visual impact and graphics were more engaging and that approaches using fear and emotion were more effective. Ineffective characteristics included complex and exaggerated information, lack of empathy and irrelevance, insufficiently specific information, extreme and death-themed content, industry messages, as well as preachy tones, animations, metaphors, dull formats, excessive length, and scenes of e-cigarette use. Conclusions Developing anti-e-cigarette campaign materials for youth necessitates target audience-focused qualitative research. This helps in deeply exploring and identifying effective themes and messages, as well as video characteristics and details while avoiding ineffective or even misleading messages and themes from young people’s perspectives outside the United States. Future development of e-cigarette prevention videos for Chinese college students may consider incorporating localized real-life testimonial cases to convey specific harms, including self-efficacy information, and utilizing fear and emotional appeals.

Abstract Accelerating a free electron to high‐energy forms the basis for studying particle and nuclear physics. Here it is shown that the wave function of such an energetic electron can be further manipulated with the femtosecond intense lasers. During the scattering between a high‐energy electron and a circularly polarized laser pulse, a regime is found where the enormous spin angular momenta of laser photons can be efficiently transferred to the electron orbital angular momentum (OAM). The wave function of the scattered electron is twisted from its initial plane‐wave state to the quantum vortex state. Nonlinear quantum electrodynamics (QED) theory suggests that the GeV‐level electrons acquire average intrinsic OAM beyond ⟨l⟩∼100ℏ at laser intensities of 1020 W cm−2 with linear scaling. These electrons emit γ‐photons with two‐peak spectrum, which sets them apart from the ordinary electrons. The findings demonstrate a proficient method for generating relativistic leptons with the vortex wave functions based on existing laser technology, thereby fostering a novel source for particle and nuclear physics.

Whey protein is an important food ingredient, but it is also considered a major food allergen. The aim of this study was to investigate the effect of ultrasound pretreatment on the structure, IgE binding capacity, functional properties and biological activity of whey protein isolate (WPI) hydrolysates (WPH), including WPI hydrolyzed by a combination of enzymes from Bromelain and ProteAXH (BA-WPI) and WPI hydrolyzed by a combination of enzymes from Papain W-40 and ProteAXH (PA-WPI). The IgE binding capacity of BA-WPI and PA-WPI was reduced to 40.28% and 30.17%, respectively, due to disruption/exposure/shielding of conformational and linear epitopes. The IgE binding capacity of sonicated WPI was increased, but ultrasound pretreatment further reduced the IgE binding capacity of the hydrolysates to 32.89% and 28.04%. This is due to the fact that ultrasound pretreatment leads to conformational changes including increased α-helix and β-sheet structure, exposure of aromatic amino acids, surface hydrophobicity, and increased sulfhydryl content, which increases the accessibility of allergenic epitopes to WPI by the enzyme. Multispectral and LC-MS/MS results further indicated that ultrasound pretreatment altered the conformational and primary structural changes of the hydrolysates. The thermograms showed that ultrasound pretreatment mainly altered the epitope spectra of β-lactoglobulin hydrolysates, while it had less effect on the epitope spectra of α-lactalbumin hydrolysates. Additionally, ultrasound pretreatment significantly improved the foaming properties, antioxidant activity, and α-glucosidase inhibition of the hydrolysates without impairing the solubility and emulsification properties of the hydrolysates. Therefore, ultrasound pretreatment is a feasible method to reduce the allergenicity of WPH and to improve their functional properties and bioactivity. Notably, ultrasonic pretreatment improved the effectiveness and efficiency of WPI hydrolysis, which is a feasible method to produce high-quality protein feedstock in a green, efficient, and economical way.

Extracellular vesicles (EVs) play an important role in normal life activities and disease treatment. In recent years, there have been abundant relevant studies focusing on EVs for cancer therapy and showing good performance on tumor inhibition. To enhance the effectiveness of EVs, EV analogs have been developed. This review summarizes the classification, origin, production, purification, modification, drug loading and cancer treatment applications of EVs and their analogs. Also, the characteristics of technologies involved are analyzed, which provides the basis for the development and application of biogenic vesicle-based drug delivery platform for cancer therapy. Meanwhile, challenges in translating these vesicles into clinic, such as limited sources, lack of production standards, and insufficient targeting and effectiveness are discussed. With ongoing exploration and clinical studies, EV-based drugs will make great contributions to cancer therapy.

ObjectiveVulvar carcinoma exhibits a robust correlation alongside HPV infection; however, the impact of HPV rank on the prognostic outcomes of radiation therapy within vulvar malignancies stays ambiguous. In the present study, we performed a comprehensive examination as well as meta-analysis to assess the influence of infection with HPV upon the long-term outlook as well as sensitivity of individuals with vulvar cancer undergoing radiation therapy.MethodsA meticulous examination of the existing research was conducted in accordance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A thorough search was conducted in the PubMed, Embase, Web of Science, as well as Cochrane Library databases, covering the entire available literature till April 1, 2023. The studies that met the inclusion criteria contained data about HPV infection and oncological outcomes in patients with vulvar cancer who received radiation therapy. This study was registered in PROSPERO (CRD42023417957).ResultsWe identified 12 retrospective studies meeting our inclusion criteria, which included a total of 3967 patients. Patients with HPV-associated vulvar cancer achieved a better overall survival rate after radiotherapy (HR=0.71, 95%CI: 0.54-0.93, P=0.01), and showed a significant improvement in disease-free survival (HR=0.75, 95%CI: 0.58-0.97, P=0.09) and progression-free survival (HR=0.31, 95%CI: 0.22-0.45, P,

Merging bound states in the continuum (BICs) and avoided crossing of resonances (ACR) are promising theoretical approaches to greatly enhance the quality (Q) factors of quasi-BICs in reciprocal space. We observe the phenomena of merging BICs and ACR in millimeter-sized C4v symmetry photonic crystal structures. The ACR at Γ point is obtained in the variation of the structural parameter. In off-Γ region, the merging BICs at arbitrary locations are observed in the experimental measurements. The findings offer a pathway to high-performance photonic devices with potential applications in optoelectronics and microwave experimentation.

Objective To explore an overcorrection quantization method and related influencing factors through analyzing relationships between the achieved and preset intrusion values of mandibular anterior teeth with clear aligners. Methods Twenty patients receiving Invisalign were recruited. The relative intrusion values in the ClinCheck software were recorded as the preset intrusion. The achieved intrusion values were measured through the digital model superimposition. Statistical analysis was conducted to assess the differences and linear relationships between the preset and achieved intrusion values, and investigate the effect of related factors such as intrusion amounts on the intrusion efficiency. Results For the mandibular anterior teeth, the mean intrusion efficiency was 62.2%, with the highest in the central incisors and the lowest in the canines. The intrusion amounts, incisors labial inclinations, and canine attachment types affected the intrusion efficiency. The differences between the preset and achieved values were significant, and the linear relationship existed. The formula of the intrusion overcorrection for the mandibular anterior teeth is “Z=(W-0.110)/0.533-W”. Z represents the overcorrection and W represents the ideal intrusion. Conclusion The preset intrusion values in the treatment protocol could not be fully achieved. Moreover, correction should be designed in cases of mandibular canine intrusion, large amountsof intrusion, orlingually inclined incisors. Compared to the optimized attachments, the vertical rectangular attachments on the mandibular canines could improve the efficiency.

Abstract Radiation enteritis is the most common complication of pelvic radiotherapy, but there is no effective prevention or treatment drug. Apoptotic T cells and their products play an important role in regulating inflammation and maintaining physiological immune homeostasis. Here it is shown that systemically infused T cell‐derived apoptotic extracellular vesicles (ApoEVs) can target mice irradiated intestines and alleviate radiation enteritis. Mechanistically, radiation elevates the synthesis of intestinal 2′3′ cyclic GMP‐AMP (cGAMP) and activates cyclic GMP‐AMP synthase (cGAS)‐stimulator of interferon genes (STING) proinflammatory pathway. After systemic infusion of ApoEVs, the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) enriches on the surface of ApoEVs hydrolyze extracellular cGAMP, resulting in inhibition of the cGAS‐STING pathway activated by irradiation. Furthermore, after ApoEVs are phagocytosed by phagocytes, ENPP1 on ApoEVs hydrolyzed intracellular cGAMP, which serves as an intracellular cGAMP hydrolyzation mode, thereby alleviating radiation enteritis. The findings shed light on the intracellular and extracellular hydrolysis capacity of ApoEVs and their role in inflammation regulation.

Abstract Objectives High‐grade gliomas (HGGs) are highly malignant, aggressive, and have a high incidence and mortality rate. The aim of this study was to investigate survival outcomes and prognostic factors in patients with HGGs. Methods In this retrospective study, a total of 159 patients with histologically confirmed HGGs were included. The recruitment period was from January 2011 to December 2019. We evaluated patient demographic data, tumor characteristics, treatment methods, immunocytochemistry results, overall survival (OS) time, and progression‐free survival (PFS) time using Kaplan–<>Meier survival analysis with log‐rank testing. Additionally, we employed Cox regression analysis to identify independent factors associated with survival outcomes. Results Kaplan–Meier survival analysis revealed that the 1‐, 2‐, and 5‐years OS rates were 81.8%, 50.3%, and 12.6%, respectively. Similarly, the 1‐, 2‐, and 5‐years PFS rates were 50.9%, 22.4%, and 3.1%, respectively. The median OS duration was 35.0 months. The univariate analysis indicated that postoperative pathological classification, grade, and age were significantly associated with patient outcomes (p

Porcine epidemic diarrhea (PED) is a highly contagious swine intestinal disease caused by PED virus (PEDV). Vaccination is a promising strategy to prevent and control PED. Previous studies have confirmed that glycosylation could regulate the immunogenicity of viral antigens. In this study, we constructed three recombinant PEDVs which removed the glycosylation sites in RBD. Viral infection assays revealed that similar replication characteristics between the recombinant viruses and parental PEDV. Although animal challenging study demonstrated that the glycosylation sites in RBD do not affect the pathogenicity of PEDV, we found that removing the glycosylation sites on the RBD regions could promote the IgG and neutralization titer in vivo, suggesting deglycosylation in RBD could enhance the immunogenicity of PEDV. These findings demonstrated that removal of the glycosylation sites in RBD is a promising method to develop PEDV vaccines.

Abstract The interplay between bacteria and their host influences the homeostasis of the human immune microenvironment, and this reciprocal interaction also affects the process of tissue damage repair. A variety of immunomodulatory commensal bacteria reside in the body, capable of delivering membrane vesicles (MVs) to host cells to regulate the local immune microenvironment. This research revealed, for the initial time, the significant enhancement of mucosal and cutaneous wound healing by MVs secreted by the human commensal Lactobacillus reuteri (RMVs) through modulation of the inflammatory environment in wound tissue. Local administration of RMVs reduces the proportion of pro‐inflammatory macrophages in inflamed tissues and mitigates the level of local inflammation, thereby facilitating the healing of oral mucosa and cutaneous wounds. The elevated oxidative stress levels in activated pro‐inflammatory macrophages can be modulated by RMVs, resulting in phenotypic transformation of macrophages. Furthermore, 3‐hydroxypropionaldehyde present in RMVs can decrease the mitochondrial permeability of macrophages and stabilize the mitochondrial membrane potential, thereby promoting the conversion of macrophages to an anti‐inflammatory phenotype. This study pioneers the significance of commensal bacterial MVs in tissue injury repair and presents a novel concept for the repair of tissue damage.

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a devastating disease that seriously threatens wheat yield and quality. To control this disease, host resistance is the most effective measure. Compared with the resistance genes from common wheat, alien resistance genes can better withstand infection of this highly variable pathogen. Development of elite alien germplasm resources with powdery mildew resistance and other key breeding traits is an attractive strategy in wheat breeding. In this study, three wheat-rye germplasm lines YT4-1, YT4-2, and YT4-3 were developed through hybridization between octoploid triticale and common wheat, out of which the lines YT4-1 and YT4-2 conferred adult-plant resistance (APR) to powdery mildew while the line YT4-3 was susceptible to powdery mildew during all of its growth stages. Using genomic in situ hybridization, multi-color fluorescence in situ hybridization, multi-color GISH, and molecular marker analysis, YT4-1, YT4-2, and YT4-3 were shown to be cytogenetically stable wheat-rye 6R addition and T1RS·1BL translocation line, 6RL ditelosomic addition and T1RS·1BL translocation line, and T1RS·1BL translocation line, respectively. Compared with previously reported wheat-rye derivative lines carrying chromosome 6R, YT4-1 and YT4-2 showed stable APR without undesirable pleiotropic effects on agronomic traits. Therefore, these novel wheat-rye 6R derivative lines are expected to be promising bridge resources in wheat disease breeding.

Abstract Background Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. Results Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. Conclusions In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.

Estimating canopy volumes of strawberry plants can be useful for predicting yields and establishing advanced management plans. Therefore, this study evaluated the spatial variability of strawberry canopy volumes using a ResNet50V2-based convolutional neural network (CNN) model trained with RGB images acquired through manual unmanned aerial vehicle (UAV) flights equipped with a digital color camera. A preprocessing method based on the You Only Look Once v8 Nano (YOLOv8n) object detection model was applied to correct image distortions influenced by fluctuating flight altitude under a manual maneuver. The CNN model was trained using actual canopy volumes measured using a cylindrical case and small expanded polystyrene (EPS) balls to account for internal plant spaces. Estimated canopy volumes using the CNN with flight altitude compensation closely matched the canopy volumes measured with EPS balls (nearly 1:1 relationship). The model achieved a slope, coefficient of determination (R2), and root mean squared error (RMSE) of 0.98, 0.98, and 74.3 cm3, respectively, corresponding to an 84% improvement over the conventional paraboloid shape approximation. In the application tests, the canopy volume map of the entire strawberry field was generated, highlighting the spatial variability of the plant’s canopy volumes, which is crucial for implementing site-specific management of strawberry crops.

The proliferation of antibiotic usage has precipitated the emergence of drug-resistant variants of bacteria, thereby augmenting their capacity to withstand pharmaceutical interventions. Among these variants, Cronobacter sakazakii (C. sakazakii), prevalent in powdered infant formula (PIF), poses a grave threat to the well-being of infants. Presently, global contamination by C. sakazakii is being observed. Consequently, research endeavors have been initiated to explore the strain’s drug resistance capabilities, alterations in virulence levels, and resistance mechanisms. The primary objective of this study is to investigate the resistance mechanisms and virulence levels of C. sakazakii induced by five distinct antibiotics, while concurrently conducting transcriptomic analyses. Compared to the susceptible strains prior to induction, the drug-resistant strains exhibited differential gene expression, resulting in modifications in the activity of relevant enzymes and biofilm secretion. Transcriptomic studies have shown that the expression of glutathione S-transferase and other genes were significantly upregulated after induction, leading to a notable enhancement in biofilm formation ability, alongside the existence of antibiotic resistance mechanisms associated with efflux pumps, cationic antimicrobial peptides, and biofilm formation pathways. These alterations significantly influence the strain’s resistance profile.

Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide, and the development of anti‐OSCC materials is urgent. The tumor microenvironment has been identified as a significant characteristic of cancer, with the pHe value in OSCC ranging from 6.56 to 6.97. Given the acidic nature of OSCC, the creation of pH‐sensitive antitumor materials has become a prominent area of research. A pH‐sensitive tertiary amine monomer, dodecylmethylaminoethyl methacrylate (DMAEM), has been previously synthesized. This study aims to evaluate the impact of DMAEM on OSCC. The results demonstrated that DMAEM inhibited the proliferation, migration, and invasion of OSCC cells. Furthermore, it promoted apoptosis and autophagy of OSCC cells, with its anti‐OSCC effect being strengthened in the acidic environment. In a subcutaneous transplantation tumor model, DMAEM inhibited the growth of OSCC and expression of Ki‐67. The analysis of 16S rDNA sequencing data revealed that DMAEM had no significant impact on the Alpha/Beta diversity of the gastrointestinal tract microbiota in mice and had minimal effect on its composition. Overall, this study suggests that DMAEM exhibits pH‐responsive behavior in the acidic tumor microenvironment, effectively inhibiting OSCC without disturbing the gastrointestinal microbiota. These findings highlight the potential of DMAEM for clinical applications in OSCC treatment.

Type 2 diabetes presents a significant global health burden and is frequently linked to serious clinical complications, including diabetic cardiomyopathy, nephropathy, and retinopathy. Astragalus polysaccharide (APS), extracted from Astragalus membranaceus, exhibits various biochemical and physiological effects. In recent years, a growing number of researchers have investigated the role of APS in glucose control and the treatment of diabetes and its complications in various diabetes models, positioning APS as a promising candidate for diabetes therapy. This review surveys the literature on APS from several databases over the past 20 years, detailing its mechanisms of action in preventing and treating diabetes mellitus. The findings indicate that APS can address diabetes by enhancing insulin resistance, modulating the immune system, protecting islet cells, and improving the intestinal microbiota. APS demonstrates positive pharmacological value and clinical potential in managing diabetic complications, including diabetic retinopathy, nephropathy, cardiomyopathy, cognitive dysfunction, wound healing, and more. However, further research is necessary to explore APS’s bioavailability, optimal dosage, and additional clinical evidence.

Abstract Sepsis poses a significant challenge in clinical management. Effective strategies targeting iron restriction, toxin neutralization, and inflammation regulation are crucial in combating sepsis. However, a comprehensive approach simultaneously targeting these multiple processes has not been established. Here, an engineered apoptotic extracellular vesicles (apoEVs) derived from macrophages is developed and their potential as multifunctional agents for sepsis treatment is investigated. The extensive macrophage apoptosis in a Staphylococcus aureus‐induced sepsis model is discovered, unexpectedly revealing a protective role for the host. Mechanistically, the protective effects are mediated by apoptotic macrophage‐released apoEVs, which bound iron‐containing proteins and neutralized α‐toxin through interaction with membrane receptors (transferrin receptor and A disintegrin and metalloprotease 10). To further enhance therapeutic efficiency, apoEVs are engineered by incorporating mesoporous silica nanoparticles preloaded with anti‐inflammatory agents (microRNA‐146a). These engineered apoEVs can capture iron and neutralize α‐toxin with their natural membrane while also regulating inflammation by releasing microRNA‐146a in phagocytes. Moreover, to exploit the microcosmic movement and rotation capabilities, erythrocytes are utilized to drive the engineered apoEVs. The erythrocytes‐driven engineered apoEVs demonstrate a high capacity for toxin and iron capture, ultimately providing protection against sepsis associated with high iron‐loaded conditions. The findings establish a multifunctional agent that combines natural and engineered antibacterial strategies.

Polycomb group RING finger (PCGF) proteins, a crucial subunits of the Polycomb complex, plays an important role in regulating gene expression, embryonic development, and cell fate determination. In our research, we investigated Pcgf5, one of the six PCGF homologs, and its impact on the differentiation of P19 cells into neural stem cells. Our findings revealed that knockdown of Pcgf5 resulted in a significant decrease in the expression levels of the neuronal markers Sox2, Zfp521, and Pax6, while the expression levels of the pluripotent markers Oct4 and Nanog increased. Conversely, Pcgf5 overexpression upregulated the expression of Sox2 and Pax6, while downregulating the expression of Oct4 and Nanog. Additionally, our analysis revealed that Pcgf5 suppresses Wnt3 expression via the activation of Notch1/Hes1, and ultimately governs the differentiation fate of neural stem cells. To further validate our findings, we conducted in vivo experiments in zebrafish. We found that knockdown of pcgf5a using morpholino resulted in the downregulated expression of neurodevelopmental genes such as sox2, sox3, and foxg1 in zebrafish embryos. Consequently, these changes led to neurodevelopmental defects. In conclusion, our study highlights the important role of Pcgf5 in neural induction and the determination of neural cell fate.

Abstract Rapid hemostasis of uncontrolled bleeding following traumatic injuries, especially accompanied by coagulopathies, remains a significant clinical challenge. Extracellular vesicles (EVs) show therapeutic effects for fast clotting. However, low yield, specific storage conditions, and lack of proper carriers have hindered EVs’ clinical application. Herein, we establish an optimized procedure method to generate lyophilized mesenchymal stem cell-derived apoptotic vesicles (apoVs) with adhesive hydrogel sponge to show superior procoagulant activity for traumatic hemorrhage. Mechanistically, apoVs’ procoagulant ability stems from their high tissue factor (TF) and phosphatidylserine (PS) expression independent of hemocytes and circulating procoagulant microparticles (cMPs). Their stable hemostatic capability was maintained after 2-month room temperature storage. Subsequently, we mixed apoVs with both phenylboronic acid grafted oxidized hyaluronic acid (PBA-HA) and poly(vinyl alcohol) (PVA) simultaneously, followed by lyophilization to construct a novel apoV-encapsulated hydrogel sponge (apoV-HS). Compared to commercial hemostats, apoV-HS exhibits rapid procoagulant ability in liver-laceration and femoral artery hemorrhage in rat and rabbit models of coagulopathies. The combination of high productivity, physiological stability, injectability, plasticity, excellent adhesivity, biocompatibility, and rapid coagulant property indicates that apoV-HS is a promising therapeutic approach for heavy hemorrhage in civilian and military populations. Graphical Abstract

Abstract Autophagosomes are double-membrane vesicles generated intracellularly to encapsulate substrates for lysosomal degradation during autophagy. Phase separated p62 body plays pivotal roles during autophagosome formation, however, the underlying mechanisms are still not fully understood. Here we describe a spatial membrane gathering mode by which p62 body functions in autophagosome formation. Mass spectrometry-based proteomics reveals significant enrichment of vesicle trafficking components within p62 body. Combining cellular experiments and biochemical reconstitution assays, we confirm the gathering of ATG9 and ATG16L1-positive vesicles around p62 body, especially in Atg2ab DKO cells with blocked lipid transfer and vesicle fusion. Interestingly, p62 body also regulates ATG9 and ATG16L vesicle trafficking flux intracellularly. We further determine the lipid contents associated with p62 body via lipidomic profiling. Moreover, with in vitro kinase assay, we uncover the functions of p62 body as a platform to assemble ULK1 complex and invigorate PI3KC3-C1 kinase cascade for PI3P generation. Collectively, our study raises a membrane-based working model for multifaceted p62 body in controlling autophagosome biogenesis, and highlights the interplay between membraneless condensates and membrane vesicles in regulating cellular functions.

Bispecific T cell engagers (BiTEs) represent a promising immunotherapy, but their efficacy against immunologically cold tumors such as pancreatic ductal adenocarcinoma remains unclear. Oncolytic viruses (OVs) can transform the immunosuppressive tumor microenvironment into the active state and also serve as transgene vectors to selectively express the desired genes in tumor cells. This study aimed to investigate whether the therapeutic benefits of tumor-targeting Claudin18.2 BiTE can be augmented by combining cancer selectively and immune-potentiating effects of OVs. Claudin18.2/CD3 BiTE was inserted into herpes simplex virus type 1 (HSV-1) to construct an OV-BiTE. Its expression and function were assessed using reporter cells and peripheral blood mononuclear cell (PBMC) co-culture assays. Intratumoral application of OV-BiTE restrained tumor growth and prolonged mouse survival compared with the unarmed OV in xenograft models and syngeneic mice bearing CLDN18.2-expressing KPC or Pan02 pancreatic cancer cells. Flow cytometry of tumor-infiltrating immune cells suggested both OV-BiTE and the unarmed OV remodeled the tumor microenvironment by increasing CD4+ T cell infiltration and decreasing regulatory T cells. OV-BiTE further reprogrammed macrophages to a more pro-inflammatory antitumor state, and OV-BiTE-induced macrophages exhibited greater cytotoxicity on the co-cultured tumor cell. This dual cytotoxic and immunomodulatory approach warrants further development for pancreatic cancer before clinical investigation.

Hutchinson–Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder that causes accelerated aging, due to a pathogenic variant in the LMNA gene. This pathogenic results in the production of progerin, a defective protein that disrupts the nuclear lamina’s structure. In our study, we conducted a histopathological analysis of various organs in the LmnaG609G/G609G mouse model, which is commonly used to study HGPS. The objective of this study was to show that progerin accumulation drives systemic but organ-specific tissue damage and accelerated aging phenotypes. Our findings show significant fibrosis, inflammation, and dysfunction in multiple organ systems, including the skin, cardiovascular system, muscles, lungs, liver, kidneys, spleen, thymus, and heart. Specifically, we observed severe vascular fibrosis, reduced muscle regeneration, lung tissue remodeling, depletion of fat in the liver, and disruptions in immune structures. These results underscore the systemic nature of the disease and suggest that chronic inflammation and fibrosis play crucial roles in the accelerated aging seen in HGPS. Additionally, our study highlights that each organ responds differently to the toxic effects of progerin, indicating that there are distinct mechanisms of tissue-specific damage.

The employment of a multi-column parallel connection is intended to enhance the energy absorption capability and reliability of surge arresters. However, the disparity in reference voltage between each varistor column and the uneven current distribution may result in a reduction in performance or even failure of the surge arrester. The objective of this study is to investigate the spiral structure of a ±550 kV DC gas-insulated switchgear (GIS) parallel arrester and its influence on the current distribution characteristics. This research develops a model of a ±550 kV DC GIS arrester and performs an in-depth theoretical analysis using multi-physics field simulations. Subsequently, a ±66 kV miniature prototype is constructed, and the accuracy of the theoretical analysis and simulation results is validated by experiments, validating the effectiveness of the proposed method. This study calculates the self-generated inductance in the spiral structure of ZnO varistors using simulations. The influence of the self-generated inductance on the current distribution of the multi-column arrester when absorbing energy is further investigated. The results indicate that the self-generated inductance of the spiral structure can reduce the current deviation factor by 28–65%. This research provides a novel approach to improving current equalization in the parallel surge arresters of DC GISs for offshore wind power converter platforms.

Abstract Background To investigate the relationship between tongue fat content and severity of obstructive sleep apnea (OSA) and its effects on the efficacy of uvulopalatopharyngoplasty (UPPP) in the Chinese group. Method Fifty-two participants concluded to this study were diagnosed as OSA by performing polysomnography (PSG) then they were divided into moderate group and severe group according to apnea hypopnea index (AHI). All of them were also collected a series of data including age, BMI, height, weight, neck circumference, abdominal circumference, magnetic resonance imaging (MRI) of upper airway and the score of Epworth Sleepiness Scale (ESS) on the morning after they completed PSG. The relationship between tongue fat content and severity of OSA as well as the association between tongue fat content in pre-operation and surgical efficacy were analyzed.Participants underwent UPPP and followed up at 3rd month after surgery, and they were divided into two groups according to the surgical efficacy. Results There were 7 patients in the moderate OSA group and 45 patients in the severe OSA group. The tongue volume was significantly larger in the severe OSA group than that in the moderate OSA group. There was no difference in tongue fat volume and tongue fat rate between the two groups. There was no association among tongue fat content, AHI, obstructive apnea hypopnea index, obstructive apnea index and Epworth sleepiness scale (all P > 0.05), but tongue fat content was related to the lowest oxygen saturation (r=-0.335, P

Abstract Using the CRITIC method, comprehensive index evaluation method, VAR model, coupling coordination model and other methods, this paper evaluates the comprehensive development of the population economy and eco-geological environment composite system in the twin-city economic circle of Chengdu–Chongqing region from 2000 to 2020, verifies the dynamic coupling relationship between subsystems and measures the coupling coordination degree of complex system. Meanwhile, the differences in the development process of each subsystem are discussed and the spatial–temporal evolution characteristics and laws of coupling coordination of the composite system during the research period are analyzed. The results reveal the following: (1) There is a long-term coordinated relationship between population, economy and eco-geological environment in Chengdu–Chongqing region, which have the conditions for emergence and generation. (2) The subsystems of population, economy and eco-geological environment in Chengdu–Chongqing region show an overall upward trend, among which the Sichuan part obviously outperforms the Chongqing part. Besides, the growth rate of the economy subsystem is significantly higher than that of the population, eco-geological environment subsystem. (3) The coupling coordinated development of the composite system has shown a benign upward development trend, gradually changing from “composite spiral structure” to “two cores outstanding, peripheral collapse, the west superior to the east”, while the main coordination state has developed from “Basic synergy—Economic lag” in 2000 to “Basic synergy—Population lag” in 2022. In addition, Cheng-De-Mian and Yuzhong districts with the better level of economic development have shown “Advanced synergy—Ecological lag”.

Abstract Background Esophageal cancer is one of the most common malignant tumors in the world, which is characterized by poor prognosis, aggressiveness, and poor survival. Mucin 13 (MUC13) is a member of the membrane-bound mucin and located on chromosome 3q21.2 and consists of α and β subunits. It has been found that MUC13 is overexpressed in a variety of tumor cells and acts a vital role in the invasiveness and malignant progression of several types of tumors. However, the role and regulatory mechanism of MUC13 in the progression of esophageal cancer remain unclear. Methods The expression level of MUC13 was detected in 15 esophageal cancer tissues and 15 pairs of adjacent nontumor tissues by immunohistochemistry (IHC). In addition, the expression of MUC13 mRNA level in human esophageal cancer cell lines (EC9706 and ECA109 and TE-1) was measured by qRT-PCR. In vitro, after silencing MUC13 with lentiviral interference technology, CCK8 assay, clone formation assay, and flow cytometry were applied to investigate the proliferation activity, clone formation ability and anti-apoptosis ability of EC9706 and ECA109 cells. The tumor xenograft growth assay was used to confirm the influence of MUC13 knockdown on the growth of esophageal tumors in vivo. The qRT-PCR assay and western blot experiments were taken to study the mechanism of MUC13 regulating the proproliferation and antiapoptotic of esophageal cancer. Results The results showed that MUC13 was overexpressed in esophageal cancer tissues and cell lines (EC9706 and ECA109 and TE-1), especially in EC9706 and ECA109 cells, but low expressed in human esophageal epithelial cell line (HEEC). Next, silencing MUC13 inhibits proliferation, blocks cell cycle progression, and promotes cell apoptosis in vitro, and restrains the growth of esophageal cancer tissues in vivo. Finally, MUC13 affects the proproliferation and antiapoptotic by regulating the expression of GLANT14, MUC3A, MUC1, MUC12, and MUC4 that closely related to O-glycan process. Conclusions This study proved that MUC13 is an important molecule that regulates the O-glycan process and then affects the progress of esophageal cancer. MUC13 may be a novel therapeutic target for patients with esophageal cancer.

Abstract BBX proteins play important roles in all of the major light-regulated developmental processes. However, no systematic analysis of BBX gene family regarding the regulation of photoperiodic microtuber formation has been previously performed in yam. In this study, a systematic analysis on the BBX gene family was conducted in three yam species, with the results, indicating that this gene plays a role in regulating photoperiodic microtuber formation. These analyses included identification the BBX gene family in three yam species, their evolutionary relationships, conserved domains, motifs, gene structure, cis-acting elements, and expressional patterns. Based on these analyses, DoBBX2/DoCOL5 and DoBBX8/DoCOL8 showing the most opposite pattern of expression during microtuber formation were selected as candidate genes for further investigation. Gene expression analysis showed DoBBX2/DoCOL5 and DoBBX8/DoCOL8 were highest expressed in leaves and exhibited photoperiod responsive expression patterns. Besides, the overexpression of DoBBX2/DoCOL5 and DoBBX8/DoCOL8 in potato accelerated tuber formation under short-day (SD) conditions, whereas only the overexpression of DoBBX8/DoCOL8 enhanced the accelerating effect of dark conditions on tuber induction. Tuber number was increased in DoBBX8/DoCOL8 overexpressing plants under dark, as well as in DoBBX2/DoCOL5 overexpressing plants under SD. Overall, the data generated in this study may form the basis of future functional characterizations of BBX genes in yam, especially regarding their regulation of microtuber formation via the photoperiodic response pathway.

Abstract Our previous studies have shown that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the intestinal microbiome could be one of the causes of non-alcoholic fatty liver disease (NAFLD). Considering antimicrobial resistance of K. pneumoniae and dysbacteriosis caused by antibiotics, phage therapy might have potential in treatment of HiAlc Kpn-induced NAFLD, because of the specificity targeting the bacteria. Here, we clarified the effectiveness of phage therapy in male mice with HiAlc Kpn-induced steatohepatitis. Comprehensive investigations including transcriptomes and metabolomes revealed that treatment with HiAlc Kpn-specific phage was able to alleviate steatohepatitis caused by HiAlc Kpn, including hepatic dysfunction and expression of cytokines and lipogenic genes. In contrast, such treatment did not cause significantly pathological changes, either in functions of liver and kidney, or in components of gut microbiota. In addition to reducing alcohol attack, phage therapy also regulated inflammation, and lipid and carbohydrate metabolism. Our data suggest that phage therapy targeting gut microbiota is an alternative to antibiotics, with potential efficacy and safety, at least in HiAlc Kpn-caused NAFLD.

Rational regulation of reactive oxygen species (ROS) plays a vital importance in maintaining homeostasis of living biological systems. For ROS-related pathologies, chemotherapy technology derived from metal nanomaterials currently occupies a pivotal position. However, they suffer from inherent issues such as complicated synthesis, batch-to-batch variability, high cost, and potential biological toxicity caused by metal elements. Here, we reported for the first time that dual-action 3,5-dihydroxy-1-ketonaphthalene-structured small-molecule enzyme imitator (DHKNase) exhibited 2-edged ROS regulation, catering to the execution of physiology-beneficial ROS destiny among diverse pathologies in living systems. Based on this, DHKNase is validated to enable remarkable therapeutic effects in 2 classic disease models, including the pathogen-infected wound-healing model and the dextran sulfate sodium (DSS)-caused inflammatory bowel disease (IBD). This work provides a guiding landmark for developing novel natural small-molecule enzyme imitator and significantly expands their application potential in the biomedical field.

Two-dimensional organic-inorganic hybrid perovskite materials are considered to have great potential for radiation detection due to their outstanding operational stability and excellent optoelectronic properties. However, most currently used single crystal (SC) growth methods impose strict requirements on growth conditions, and their potential effectiveness also faces significant challenges, especially for those perovskite systems with significant differences in solubility between raw materials and target products. In this study, a dynamic seed rotation method was developed to relieve the above dilemma. With the help of this method, centimeter-sized high-quality [(TMOD)2PbBr4]5·H2O (TMOD is thiomorpholine-1,1-dioxide) SCs were harvested. X-ray detectors based on the as-prepared SC exhibit a high sensitivity of 5.35 × 103 μC Gyair−1 cm−2 and a low detection limit of 3.1 nGyair s−1. We believe this strategy can also be applied to the preparation of other perovskite materials, paving the way for the application of high-quality optoelectronic devices.

IntroductionMacao has been certified as a “Healthy City” by the World Health Organization, and has been adhering to the principle of combining prevention with proper medical care to build its medical system. As tobacco epidemic is a risk factor leading to a series of non-communicable diseases, the Macao SAR Government has continuously improved tobacco control measures.MethodsThe data for this study were derived from a news report on “e-cigarettes” published in Macao Daily. Co-word analysis and thematic analysis were conducted to analyze the development of tobacco control legislation against e-cigarettes. Co-word analysis examined the association and frequency of keywords, while thematic analysis identified prevalent themes within the data.ResultsThe study identified three stages of legislation against e-cigarettes: the pre-implementation stage, the early implementation stage, and the epidemic period. Each stage exhibited distinct characteristics and attention toward specific groups, particularly “teenagers” and “students,” increased significantly. Thematic analysis further highlighted the potential issues of drug use and smuggling associated with e-cigarettes.DiscussionThe findings suggest that the Macao SAR Government should prioritize the development of healthy behaviors among adolescents in the context of e-cigarette control. Additionally, considering regional cooperation to promote the “Healthy Bay Area” could be beneficial. Social media platforms and effective data management should be utilized as tools in these efforts.

AbstractObjective To report an extremely rare case of bladder cancer patient with cervical lymph nodes, abdominal lymph nodes, and bone metastases at the same time.Methods and results The case was investigated by follow-up and immunohistochemistry was used in the pathological part.Result The patient was diagnosed with bladder cancer (high-grade urothelial metastatic epithelial cell carcinoma) by pathology and immunohistochemistry after transurethral resection of bladder tumor (TURBT) and metastatic bladder cancer by pathology and immunohistochemistry after cervical lymph node aspiration due to neck lymph node enlargement 1 year later, and a CT of the chest and abdomen suggested that the patient also had abdominal lymph node and bone metastases.At the 2.5-year regular chemotherapy follow-up, the patient showed that the abdominal lymph node metastasis disappeared, the cervical lymph node fusion shrank, and the bone metastasis still existed.Conclusion 1. Regular postoperative review is particularly important; 2.For patients with UCB who undergo TURBT, a effective regular perfusion program should be performed throughout the postoperative period; 3. For patients with postoperative metastatic symptoms of UCB, Complex treatment has a positive effect on patient prognosis; 4.The presence of enlarged head and neck lymph nodes in patients with bladder cancer should also be considered as metastatic of UCB.

Kallikrein 8(KLK8) is closely related to the central nervous system and is involved in the pathological processes of many neurological diseases by altering inter-synaptic adhesion relationships and extracellular matrix molecules thereby modifying synaptic morphology and regulating synaptic plasticity. In this paper, we review the role and pathogenesis of KLK8 in neurological disorders such as dysthymic disorders, Alzheimer's disease, epilepsy, and multiple sclerosis with respect to its physiological properties. It is expected to provide a theoretical basis for the diagnosis and prognosis of neurological diseases and provide directions for the research of such diseases.

Eddy current testing (ECT) is commonly used for the detection of defects inside metallic materials. In order to achieve the effective testing of CFRP materials, increasing the operating frequency or improving the coil structure is a common method used by researchers. Higher or wider operating frequencies make the design of the ADC’s conditioning circuit complex and difficult to miniaturize. In this paper, an LC resonator based on inductance-to-digital converters (LDCs) is designed to easily detect the resonant frequency response to the state of the material under test. The reasonableness of the coil design is proven by simulation. The high signal-to-noise ratio (SNR) and detection sensitivity of the LC resonator are demonstrated through comparison experiments involving multiple probes. The anti-interference capability of the LC resonator in CFRP defect detection is demonstrated through various interference experiments.

This research aimed to examine the mediating effect of intrusive imagery and fear of negative evaluation on the connection between body dissatisfaction and smartphone addiction. 5,909 participants were included in the research, with 53.8% of the sample being female. The average age of the participants was 19.87 years, and their ages ranged from 18 to 32 years. All individuals who were recruited for the study successfully finished the Satisfaction and Dissatisfaction with Body Parts Scale, the Smartphone Addiction Scale, the Intrusive Imagery Scale, and the Fear of Negative Evaluation Scale. Mediational analysis indicated that, with age, gender and body mass index under control, body dissatisfaction was linked to smartphone addiction via (1) the mediating role of intrusive imagery, (2) the mediating role of fear of negative evaluation, and (3) the serial mediating role of intrusive imagery and fear of negative evaluation. Our study for the first time advanced our understanding that intrusive imagery and fear of negative evaluation could be serial mediators of the relationship between body dissatisfaction and smartphone addiction. However, the cross-sectional design prevented us from establishing causality between these variables, which could be better examined in future longitudinal studies.