Assembly and comparative analysis of the complete mitochondrial genome of Brassica rapa var. Purpuraria.

BACKGROUND: Purple flowering stalk (Brassica rapa var. purpuraria) is a widely cultivated plant with high nutritional and medicinal value and exhibiting strong adaptability during growing. Mitochondrial (mt) play important role in plant cells for energy production, developing with an independent genetic system. Therefore, it is meaningful to assemble and annotate the functions for the mt genome of plants independently. Though there have been several reports referring the mt genome of in Brassica species, the genome of mt in B. rapa var. purpuraria and its functional gene variations when compared to its closely related species has not yet been addressed. RESULTS: The mt genome of B. rapa var. purpuraria was assembled through the Illumina and Nanopore sequencing platforms, which revealed a length of 219,775 bp with a typical circular structure. The base composition of the whole B. rapa var. purpuraria mt genome revealed A (27.45%), T (27.31%), C (22.91%), and G (22.32%). 59 functional genes, composing of 33 protein-coding genes (PCGs), 23 tRNA genes, and 3 rRNA genes, were annotated. The sequence repeats, codon usage, RNA editing, nucleotide diversity and gene transfer between the cp genome and mt genome were examined in the B. rapa var. purpuraria mt genome. Phylogenetic analysis show that B. rapa var. Purpuraria was closely related to B. rapa subsp. Oleifera and B. juncea. Ka/Ks analysis reflected that most of the PCGs in the B. rapa var. Purpuraria were negatively selected, illustrating that those mt genes were conserved during evolution. CONCLUSIONS: The results of our findings provide valuable information on the B.rapa var. Purpuraria genome, which might facilitate molecular breeding, genetic variation and evolutionary researches for Brassica species in the future.

Dysfunction of Avo3, an essential component of target of rapamycin complex 2, induces ubiquitin-proteasome-dependent downregulation of Avo2 in Saccharomyces cerevisiae.

The ubiquitin-proteasome system (UPS) plays a key role in maintaining cellular protein homeostasis and participates in modulating various cellular functions. Target of rapamycin (TOR), a highly conserved Ser/Thr kinase found across species from yeasts to humans, forms two multi-protein complexes, TORC1 and TORC2, to orchestrate cellular processes crucial for optimal growth, survival, and stress responses. While UPS-mediated regulation of mammalian TOR complexes has been documented, the ubiquitination of yeast TOR complexes remains largely unexplored. Here we report a functional interplay between the UPS and TORC2 in Saccharomyces cerevisiae. Using avo3-2ts, a temperature-sensitive mutant of the essential TORC2 component Avo3 exhibiting TORC2 defects at restrictive temperatures, we obtained evidence for UPS-dependent protein degradation and downregulation of the TORC2 component Avo2. Our results established the involvement of the E3 ubiquitin ligase Ubr1 and its catalytic activity in mediating Avo2 degradation in cells with defective Avo3. Coimmunoprecipitation revealed the interaction between Avo2 and Ubr1, indicating Avo2 as a potential substrate of Ubr1. Furthermore, depleting Ubr1 rescued the growth of avo3-2ts cells at restrictive temperatures, suggesting an essential role of Avo2 in sustaining cell viability under heat stress and/or TORC2 dysfunction. This study uncovers a role of UPS in yeast TORC2 regulation, highlighting the impact of protein degradation control on cellular signaling.

Synthesis of Nanosized γ-Cyclodextrin Metal-Organic Frameworks as Carriers of Limonene for Fresh-Cut Fruit Preservation Based on Polycaprolactone Nanofibers.

To address the issue of bacterial growth on fresh-cut fruits, this paper reports the synthesis of nanosized γ-cyclodextrin metal-organic frameworks (CD-MOFs) using an ultrasound-assisted method and their application as carriers of limonene for antibacterial active packaging. The effects of the processing parameters on the morphology and crystallinity of the CD-MOFs are investigated, and the results prove that the addition of methanol is the key to producing nanosized CD-MOFs. The limonene loading content of the nanosized CD-MOFs can reach approximately 170 mg g-1. The sustained-release behaviors of limonene in the CD-MOFs are evaluated. Molecular docking simulations reveal the distribution and binding sites of limonene in the CD-MOFs. CD-MOFs are deposited on the surfaces of polycaprolactone (PCL) nanofibers via an immersion method, and limonene-loaded CD-MOF@PCL nanofibers are prepared. The morphology, crystallinity, thermal stability, mechanical properties, and antibacterial activity of the nanofibers are also studied. The nanofiber film effectively inhibits bacterial growth and prolongs the shelf life of fresh-cut apples. This study provides a novel strategy for developing antibacterial active packaging materials based on CD-MOFs and PCL nanofibers.

SARS-CoV-2 spike-FLIPr fusion protein plus lipidated FLIPr protects against various SARS-CoV-2 variants in hamsters.

Vaccine-induced mucosal immunity and broad protective capacity against various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remain inadequate. Formyl peptide receptor-like 1 inhibitory protein (FLIPr), produced by Staphylococcus aureus, can bind to various Fcγ receptor subclasses. Recombinant lipidated FLIPr (rLF) was previously found to be an effective adjuvant. In this study, we developed a vaccine candidate, the recombinant Delta SARS-CoV-2 spike (rDS)-FLIPr fusion protein (rDS-F), which employs the property of FLIPr binding to various Fcγ receptors. Our study shows that rDS-F plus rLF promotes rDS capture by dendritic cells. Intranasal vaccination of mice with rDS-F plus rLF increases persistent systemic and mucosal antibody responses and CD4/CD8 T-cell responses. Importantly, antibodies induced by rDS-F plus rLF vaccination neutralize Delta, Wuhan, Alpha, Beta, and Omicron strains. Additionally, rDS-F plus rLF provides protective effects against various SARS-CoV-2 variants in hamsters by reducing inflammation and viral loads in the lung. Therefore, rDS-F plus rLF is a potential vaccine candidate to induce broad protective responses against various SARS-CoV-2 variants.IMPORTANCEMucosal immunity is vital for combating pathogens, especially in the context of respiratory diseases like COVID-19. Despite this, most approved vaccines are administered via injection, providing systemic but limited mucosal protection. Developing vaccines that stimulate both mucosal and systemic immunity to address future coronavirus mutations is a growing trend. However, eliciting strong mucosal immune responses without adjuvants remains a challenge. In our study, we have demonstrated that using a recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-formyl peptide receptor-like 1 inhibitory protein (FLIPr) fusion protein as an antigen, in combination with recombinant lipidated FLIPr as an effective adjuvant, induced simultaneous systemic and mucosal immune responses through intranasal immunization in mice and hamster models. This approach offered protection against various SARS-CoV-2 strains, making it a promising vaccine candidate for broad protection. This finding is pivotal for future broad-spectrum vaccine development.

Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia.

Background: Satisfactory responses can be obtained for acute myeloid leukemia (AML) treated by Venetoclax (VEN)-based therapy. However, there are still quite a few AML patients (AMLs) resistant to VEN, and it is critical to understand whether VEN-resistance is regulated by senescence. Methods: Here, we established and validated a signature for predicting AML prognosis based on VEN resistance-related senescence genes (VRSGs). In this study, 51 senescence genes were identified with VEN-resistance in AML. Using LASSO algorithms and multiple AML cohorts, a VEN-resistance senescence prognostic model (VRSP-M) was developed and validated based on 6-senescence genes. Results: According to the median score of the signature, AMLs were classified into two subtypes. A worse prognosis and more adverse features occurred in the high-risk subtype, including older patients, non-de novo AML, poor cytogenetics, adverse risk of European LeukemiaNet (ELN) 2017 recommendation, and TP53 mutation. Patients in the high-risk subtype were mainly involved in monocyte differentiation, senescence, NADPH oxidases, and PD1 signaling pathway. The model's risk score was significantly associated with VEN-resistance, immune features, and immunotherapy response in AML. In vitro, the IC50 values of ABT-199 (VEN) rose progressively with increasing expression of G6PD and BAG3 in AML cell lines. Conclusions: The 6-senescence genes prognostic model has significant meaning for the prediction of VEN-resistance, guiding personalized molecularly targeted therapies, and improving AML prognosis.

Slow Release of GA3 Hormone from Polymer Coating Overcomes Seed Dormancy and Improves Germination.

Seed dormancy often hinders direct seeding efforts that are attempting to restore degraded landscapes. Gibberellic acid (GA3) can be applied to physiologically dormant seeds to induce germination, but this hormone is rarely effective, as it can degrade or be leached from the seed. We tested different polymer matrixes (polylactic acid, polyvinylpyrrolidone, and ethylcellulose) to apply and slowly release GA3 to the seed. These polymers were tested as seed coatings in either a powder, liquid, or a combination of powder and liquid forms. We found that a liquid ethylcellulose/GA3 coating generally outperformed the other polymers and applications methods using our test species Penstemon palmeri. With this top-performing treatment, seed germination was 3.0- and 3.9-fold higher at 15 °C and 25 °C, respectively. We also evaluated the liquid ethylcellulose/GA3 coating on P. comharrenus, P. strictus, P. pachyphyllus, and P. eatonii. Again, the coating had a strong treatment response, with the degree of difference related to the relative level of dormancy of the species. Growth studies were also performed in pots to ensure that the side effects of GA3 overdosing were not present. Here, we found minimal differences in root length, shoot length, or biomass between plants grown from untreated and GA3-coated seeds.

Single-cell analysis of human prepuce reveals dynamic changes in gene regulation and cellular communications.

BACKGROUND: The cellular and molecular dynamics of human prepuce are crucial for understanding its biological and physiological functions, as well as the prevention of related genital diseases. However, the cellular compositions and heterogeneity of human prepuce at single-cell resolution are still largely unknown. Here we systematically dissected the prepuce of children and adults based on the single-cell RNA-seq data of 90,770 qualified cells. RESULTS: We identified 15 prepuce cell subtypes, including fibroblast, smooth muscle cells, T/natural killer cells, macrophages, vascular endothelial cells, and dendritic cells. The proportions of these cell types varied among different individuals as well as between children and adults. Moreover, we detected cell-type-specific gene regulatory networks (GRNs), which could contribute to the unique functions of related cell types. The GRNs were also highly dynamic between the prepuce cells of children and adults. Our cell-cell communication network analysis among different cell types revealed a set of child-specific (e.g., CD96, EPO, IFN-1, and WNT signaling pathways) and adult-specific (e.g., BMP10, NEGR, ncWNT, and NPR1 signaling pathways) signaling pathways. The variations of GRNs and cellular communications could be closely associated with prepuce development in children and prepuce maintenance in adults. CONCLUSIONS: Collectively, we systematically analyzed the cellular variations and molecular changes of the human prepuce at single-cell resolution. Our results gained insights into the heterogeneity of prepuce cells and shed light on the underlying molecular mechanisms of prepuce development and maintenance.

[Inhibition of M2 macrophage polarization and reduction of airway inflammation in asthmatic mice with lncRNA MRAK088388 knockout].

Objective To investigate the long non-coding RNA(lncRNA) MRAK08838 regulates macrophage function to influence the development of asthmatic airway inflammation. Methods MRAK088388 gene knockout (MRAK088388-/-) mouse model was prepared and allergic asthma was induced by dust mite protein Dermatophagoides farinae 1 (Der f1). The mice were sacrificed after 28 days of modeling, and serum was collected to measure IgE and IgG. The FinePointe RC system was used to measure airway hyperresponsiveness and evaluate lung function in mice. Lung tissue was taken for HE staining, and periodic acid-Schiff (PAS) staining was used to evaluate inflammatory infiltration and mucus secretion in mouse lungs. Fluorescence quantitative PCR was used to detect the expression level of lncRNA MRAK08838 in bronchoalveolar lavage fluid (BALF) cells and lung tissue of asthmatic mice. ELISA was used to detect the levels of inflammatory cytokines IFN-γ, IL-4, IL-5, IL-13, IL-10 and IL-17A. Flow cytometry was used to evaluate the phenotype of macrophages in BALF and lung tissue, as well as the proportion of neutrophils, eosinophils, and alveolar macrophages. The changes of the above indicators were detected in mice by adoptive transfer of bone marrow-derived macrophages (BMDM). Results Under the challengle of Der f1, MRAK088388-/- mice showed reduced allergic airway inflammation, including reduced eosinophils in BALF and reduced production of IgE and IgG1. In addition, Der f1-treated MRAK088388-/- mice had fewer M2 macrophages than wild-type asthmatic mice. Wild-type mouse BMDM (M0) and Der f1-treated MRAK088388-/- mice also showed mild inflammatory response. Conclusion Knockout of MRAK088388 alleviates airway inflammation in asthmatic mice by inhibiting M2 polarization of airway macrophages.

Novel GdTaO4 phase for efficient photocatalytic degradation of organic dye under visible light irradiation: An X-ray spectroscopic investigation.

The novel GdTaO4 phase exhibits good photocatalytic activity under visible light irradiation and holds great promise for the removal of organic dyes from industrial wastes. The GdTaO4 samples were synthesized using the hydrothermal and calcination process with different weight ratios of gadolinium nitrate hydrate (G) and tantalum pentachloride (T), and their structural studies confirmed the formation of the GdTaO4 (GT) phase. Among the samples, GT-4 (with a weight ratio of 4:1) exhibited the highest photocatalytic activity for the degradation of Methyl Orange (MO) dye under visible light irradiation. To enhance the photocatalytic performance, H2O2 was used as a green additive, and the photocatalytic abilities were examined by varying dye types and concentrations. X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectroscopy (XAS) revealed the local atomic and electronic structures around Ta and Gd and highlighted the contribution of Gd3+ to the GT system, which is a crucial factor in supporting the enhanced photocatalytic performance. Moreover, in-situ XAS at Gd M5-edge and O K-edge were examined under illumination/dark conditions to explore the electronic structures of photo-excited electron transition in the photocatalytic process. The analytical results provided strong evidence correlating the electronic structure and photocatalytic property of the GT. This study demonstrates that GdTaO4 exhibits good photocatalytic activity under visible light irradiation, making it a promising new Ta-based photocatalyst for the effective removal of organic dyes from industrial wastes.

Defect-Rich SnO2 Nanofiber as an Oxygen-Defect-Driven Photoenergy Shield against UV Light Cell Damage.

Usually, most studies focus on toxic gas and photosensors by using electrospinning and metal oxide polycrystalline SnO2 nanofibers (PNFs), while fewer studies discuss cell-material interactions and photoelectric effect. In this work, the controllable surface morphology and oxygen defect (VO) structure properties were provided to show the opportunity of metal oxide PNFs to convert photoenergy into bio-energy for bio-material applications. Using the photobiomodulation effect of defect-rich polycrystalline SnO2 nanofibers (PNFs) is the main idea to modulate the cell-material interactions, such as adhesion, growth direction, and reactive oxygen species (ROS) density. The VO structures, including out-of-plane oxygen defects (op-VO), bridge oxygen defects (b-VO), and in-plane oxygen defects (ip-VO), were studied using synchrotron analysis to investigate the electron transfer between the VO structures and conduction bands. These intragrain VO structures can be treated as generation-recombination centers, which can convert various photoenergies (365-520 nm) into different current levels that form distinct surface potential levels; this is referred to as the photoelectric effect. PNF conductivity was enhanced 53.6-fold by enlarging the grain size (410 nm2) by increasing the annealing temperature, which can improve the photoelectric effect. In vitro removal of reactive oxygen species (ROS) can be achieved by using the photoelectric effect of PNFs. Also, the viability and shape of human bone marrow mesenchymal stem cells (hMSCs-BM) were also influenced significantly by the photobiomodulation effect. The cell damage and survival rate can be prevented and enhanced by using PNFs; metal oxide nanofibers are no longer only environmental sensors but can also be a bio-material to convert the photoenergy into bio-energy for biomedical science applications.

Clinical features and prognostic significance of DNMT3A, FLT3, and NPM1 mutations in de novo acute myeloid leukemia patients.

OBJECTIVE: Different co-mutation patterns are associated with varied clinical manifestations and prognosis. The purpose of this research was to explore the clinical characteristics and prognosis of individuals with AML who had DNMT3A, FLT3, and NPM1 mutations. MATERIALS AND METHODS: A total of 259 newly diagnosed AML patients were investigated in this study, including 148 AMLFLT3mutDNMT3Awt , 48 AMLFLT3wtDNMT3Amut , and 63 AMLFLT3mutDNMT3Amut patients. Mutations were detected by targeted next-generation sequencing and Sanger sequencing. In addition, we utilized the publicly available data to analyze the expression profiles of AML. RESULTS: Correlation analysis showed NPM1 mutations were positively associated with FLT3-ITD and DNMT3A, but negatively with CEBPA and RUNX1 mutations. In the presence of both DNMT3A and FLT3 mutations, patients were associated with typical clinical manifestations such as heavy disease burden and old age. Patients with both FLT3 and DNMT3A mutations had lower complete remission rates and poorer clinical outcomes than those with FLT3 or DNMT3A mutation alone. Univariate analysis showed that age, response to treatment, DNMT3A R882 mutation, NPM1 mutation, and consolidation treatment options were associated with OS. According to multivariate analysis, only consolidation treatment options could be considered as an independent prognostic factor. In addition, the percentage of AMLFLT3mutDNMT3AmutNPM1mut patients in our study was about 5.9%. Interestingly, the expression profile of this subgroup was significantly related to HOX family and histone H1 family, and enriched pathways associated with transcriptional misregulation. CONCLUSION: We comprehensively evaluated the clinical and genetic characteristics, and expression profiles of AML patients with common mutations, and found that AML patients with triple mutations might be a distinct AML subtype, which should be redefined.

Comprehensive Analysis of lncRNA-mRNA Expression Profiles in Depression-like Responses of Mice Related to Polystyrene Nanoparticle Exposure.

Plastics in the environment can break down into nanoplastics (NPs), which pose a potential threat to public health. Studies have shown that the nervous system constitutes a significant target for nanoplastics. However, the potential mechanism behind nanoplastics' neurotoxicity remains unknown. This study aimed to investigate the role of lncRNA in the depressive-like responses induced by exposure to 25 nm polystyrene nanoplastics (PS NPs). Forty mice were divided into four groups administered doses of 0, 10, 25, and 50 mg/kg via gavage for 6 months. After conducting behavioral tests, RNA sequencing was used to detect changes in mRNAs, miRNAs, and lncRNAs in the prefrontal cortex of the mice in the 0 and 50 mg/kg PS NPs groups. The results revealed that mice exposed to chronic PS NPs developed depressive-like responses in a dose-dependent manner. It was demonstrated that 987 mRNAs, 29 miRNAs, and 116 lncRNAs were significantly different between the two groups. Then, a competing endogenous RNA (ceRNA) network containing 6 lncRNAs, 18 miRNAs, and 750 mRNAs was constructed. Enrichment results suggested that PS NPs may contribute to the onset of depression-like responses through the activation of axon guidance, neurotrophin-signaling pathways, and dopaminergic synapses. This study provided evidence of the molecular relationship between PS NPs and depression-like responses.

Recombinant lipidated FLIPr effectively enhances mucosal and systemic immune responses for various vaccine types.

Formyl peptide receptor-like 1 inhibitor protein (FLIPr) is an immune evasion protein produced by Staphylococcus aureus, and FLIPr is a potential vaccine candidate for reducing Staphylococcus aureus virulence and biofilm formation. We produced recombinant lipidated FLIPr (rLF) to increase the immunogenicity of FLIPr and showed that rLF alone elicited potent anti-FLIPr antibody responses to overcome the FLIPr-mediated inhibition of phagocytosis. In addition, rLF has potent immunostimulatory properties. We demonstrated that rLF is an effective adjuvant. When an antigen is formulated with rLF, it can induce long-lasting antigen-specific immune responses and enhance mucosal and systemic antibody responses as well as broad-spectrum T-cell responses in mice. These findings support further exploration of rLF in the clinic as an adjuvant for various vaccine types with extra benefits to abolish FLIPr-mediated immunosuppressive effects.

Site-specific Atg13 methylation-mediated autophagy regulates epithelial inflammation in PM2.5-induced pulmonary fibrosis.

Fine particulate matters (PM2.5) increased the risk of pulmonary fibrosis. However, the regulatory mechanisms of lung epithelium in pulmonary fibrosis remained elusive. Here we developed PM2.5-exposure lung epithelial cells and mice models to investigate the role of autophagy in lung epithelia mediating inflammation and pulmonary fibrosis. PM2.5 exposure induced autophagy in lung epithelial cells and then drove pulmonary fibrosis by activation of NF-κB/NLRP3 signaling pathway. PM2.5-downregulated ALKBH5 protein expression promotes m6A modification of Atg13 mRNA at site 767 in lung epithelial cells. Atg13-mediated ULK complex positively regulated autophagy and inflammation in epithelial cells with PM2.5 treatment. Knockout of ALKBH5 in mice further accelerated ULK complex-regulated autophagy, inflammation and pulmonary fibrosis. Thus, our results highlighted that site-specific m6A methylation on Atg13 mRNA regulated epithelial inflammation-driven pulmonary fibrosis in an autophagy-dependent manner upon PM2.5 exposure, and it provided target intervention strategies towards PM2.5-induced pulmonary fibrosis.

Reversible organohydrogels based on dynamic hydrogen bonding among water, dimethyl sulfoxide, and polyethylene glycol.

Facile gelation and degelation have been achieved by dynamic hydrogen bonding among dimethyl sulfoxide, water, and polyethylene glycol to prepare anti-freezing, drying-resistant, strongly thixotropic, and water-sensitive organohydrogels that are significant for biomaterial protection and storage.

Low-Temperature-Tolerant Strain-Sensing Flexible Composite for Soft Body Armor.

Developing soft body armor with sensing characteristics in various application scenarios is a challenge but important for creating a peaceful world and personal safety, whereas existing materials suffer from indefinite protective effects and stimulus response at subzero temperatures in the long term. Herein, an anti-freezing and flexible puncture-resistance composite with strain-sensing ability is developed by compounding a NaCl-soaked poly(vinyl alcohol) (PVA)/sodium alginate (SA)/glycerol (Gly) hydrogel (PSGN hydrogel) with Kevlar fabric. After freezing-thawing treatment once and NaCl immersion for 10 h, the Kevlar/PSGN-10 composite has excellent puncture-resistance properties and linear, rapid response, wide band, and stable strain-sensing behaviors at 25 and -30 °C. The composite's maximum puncturing force and energy dissipation at -30 °C are 53.92 N and 370 mJ, respectively, increased by 285 and 302% compared with neat Kevlar fabric. The flexibility reduction and the mass addition of the Kevlar/PSGN-10 composite are merely 19 and 40%, respectively, showing superior wearable comfortability and protection efficiency. The composites also reveal remarkable strain-sensing abilities at -30 °C (linear strain sensitivity with GF = 0.27 and R2 = 0.981, a wide working frequency range of 0.16-1.3 Hz, and sensing stability for 1500 cycles). Moreover, the composite could respond to multipart body motion directly, including fingers, elbows, wrists, and knees. Consequently, the Kevlar/PSGN composite developed in this paper is promising for intelligent soft body armor at various temperatures.

Machine learning-based drug design for identification of thymidylate kinase inhibitors as a potential anti-Mycobacterium tuberculosis.

The rise of antibiotic-resistant Mycobacterium tuberculosis (Mtb) has reduced the availability of medications for tuberculosis therapy, resulting in increased morbidity and mortality globally. Tuberculosis spreads from the lungs to other parts of the body, including the brain and spine. Developing a single drug can take several decades, making drug discovery costly and time-consuming. Machine learning algorithms like support vector machines (SVM), k-nearest neighbor (k-NN), random forest (RF) and Gaussian naive base (GNB) are fast and effective and are commonly used in drug discovery. These algorithms are ideal for the virtual screening of large compound libraries to classify molecules as active or inactive. For the training of the models, a dataset of 307 was downloaded from BindingDB. Among 307 compounds, 85 compounds were labeled as active, having an IC50 below 58 mM, while 222 compounds were labeled inactive against thymidylate kinase, with 87.2% accuracy. The developed models were subjected to an external ZINC dataset of 136,564 compounds. Furthermore, we performed the 100-ns dynamic simulation and post trajectories analysis of compounds having good interaction and score in molecular docking. As compared to the standard reference compound, the top three hits revealed greater stability and compactness. In conclusion, our predicted hits can inhibit thymidylate kinase overexpression to combat Mycobacterium tuberculosis.Communicated by Ramaswamy H. Sarma.

CRISPR-based quantum dot nanobead lateral flow assay for facile detection of varicella-zoster virus.

Varicella-zoster virus (VZV) infects more than 90% of the population worldwide and has a high incidence of postherpetic neuralgia in elderly patients, seriously affecting their quality of life. Combined with clustered regularly interspaced short palindromic repeats (CRISPR) system, we develop a quantum dot nanobeads (QDNBs) labeled lateral flow assay for VZV detection. Our assay allows the identification of more than 5 copies of VZV genomic DNA in each reaction. The entire process, from sample preparation to obtaining the results, takes less than an hour. In 86 clinical vesicles samples, the test shows 100% concordance with quantitative real-time PCR for VZV detection. Notably, when vesicles are present in specific areas, such as the genitals, our method outperforms clinical diagnosis. Compared to traditional detection methods, only a minute amount of blister fluid is required for accurate detection. Therefore, we anticipate that our method could be translated to clinical applications for specific and rapid VZV detection. KEY POINTS: • CRISPR/Cas12a and quantum dot nanobead-based lateral flow assay achieved 5 copies per reaction for VZV detection • Specific identification of VZV in atypical skin lesions • Results read by the naked eye within one hour.

Luteolin-Loaded Nanoparticles for the Treatment of Melanoma.

Background and Purpose: Luteolin (LUT), a flavonoid found in various plants, has been reported to have potential therapeutic effects in melanoma. However, poor water solubility and low bioactivity have severely restricted the clinical application of LUT. Based on the high reactive oxygen species (ROS) levels in melanoma cells, we developed nanoparticles encapsulating LUT with the ROS-responsive material poly(propylene sulfide)-poly(ethylene glycol) (PPS-PEG) to enhance the water solubility of LUT, accelerate the release of LUT in melanoma cells, and further enhance its anti-melanoma effect, providing a viable solution for the application of LUT nano-delivery systems in melanoma therapy. Methods: In this study, LUT-loaded nanoparticles were prepared with PPS-PEG and named as LUT-PPS-NPs. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were applied to determine the size and morphology of LUT-PPS-NPs. In vitro studies were carried out to determine the uptake and mechanism of LUT-PPS-NPs by SK-MEL-28 melanoma cells. According to the CCK-8 assay, the cytotoxic effects of LUT-PPS-NPs on human skin fibroblasts (HSF) and SK-MEL-28 cells were assessed. Apoptosis assays, cell migration and invasion assays, and proliferation inhibition assays with low and normal density plating were also applied to test the in vitro anti-melanoma effect. Additionally, melanoma models were established utilizing BALB/c nude mice and initially evaluated the growth inhibitory impact following intratumoral injection of LUT-PPS-NPs. Results: The size of LUT-PPS-NPs was 169.77 ± 7.33 nm with high drug loading (15.05 ± 0.07%). In vitro, cellular assays confirmed that LUT-PPS-NPs were efficiently internalized by SK-MEL-28 cells and showed low cytotoxicity against HSF. Moreover, LUT released from LUT-PPS-NPs significantly inhibited tumor cell proliferation, migration and invasion. Animal experiments showed that LUT-PPS-NPs inhibited tumor growth more than 2-fold compared with the LUT group. Conclusion: In conclusion, the LUT-PPS-NPs developed in our study enhanced the anti-melanoma effect of LUT.

Synthesis and properties of SiO2/SiO2@Ag two-phase STFs.

Soft body armor with a strain-sensing function using conductive shear thickening fluids (STFs) has gradually gained research interest. In this study, conductive SiO2@Ag core-shell microspheres were synthesized and the influence of process parameters on their properties was evaluated. Subsequently, SiO2 and SiO2@Ag were used as dispersed phases to prepare two-phase STFs, the effect of the core-shell microspheres' proportion on the rheological properties of the STFs was investigated, and its mechanism was discussed. The results indicated that SiO2@Ag core-shell microspheres were coated with elemental silver and when the concentration of sodium hydroxide and glucose were 0.07 and 0.09 mol L-1, respectively, the coating surface was the most uniform and compact, and the conductivity reached the minimum value of 0.56 Ω cm. The two-phase STFs exhibited good and reversible shear thickening behaviors and the critical shear rate decreased with increasing core-shell microsphere concentration. Additionally, when the mass fraction of SiO2 and SiO2@Ag core-shell microspheres was 45% and 20%, respectively, the thickening rate was 325%, and the resistance of two-phase STFs decreased simultaneously with the emergence of shear thickening that reached the lowest value of 795.16 kΩ. This study provides a novel strategy for synthesizing conductive STFs for strain-sensing flexible stab-resistant composites.