Protection of the receptor binding domain (RBD) dimer against SARS-CoV-2 and its variants.

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants achieved immune escape and became less virulent and easily transmissible through rapid mutation in the spike protein, thus the efficacy of vaccines on the market or in development continues to be challenged. Updating the vaccine, exploring compromise vaccination strategies, and evaluating the efficacy of candidate vaccines for the emerging variants in a timely manner are important to combat complex and volatile SARS-CoV-2. This study reports that vaccines prepared from the dimeric receptor-binding domain (RBD) recombinant protein, which can be quickly produced using a mature and stable process platform, had both good immunogenicity and protection in vivo and could completely protect rodents from lethal challenge by SARS-CoV-2 and its variants, including the emerging Omicron XBB.1.16, highlighting the value of dimeric recombinant vaccines in the post-COVID-19 era.

Construction of Carbon Dots@LiCl-polyacrylamide with Humidity-Induced Ultralong Room-Temperature Phosphorescence to Fluorescence and Rigid-to-Flexible Transition Behavior.

The continuous advancement of luminescent materials has placed increasingly stringent requirements on dynamic color-tunable ultralong room-temperature phosphorescence (URTP) materials that can respond to external stimuli. Nevertheless, endowing URTP materials with stimuli-response-induced dynamic color tuning is a challenging task. This study introduces a carbon dots (CDs)@LiCl-polyacrylamide (PAM) polymer system that switches from URTP to fluorescence under humidity stimuli, accompanied by a transition from rigidity to flexibility. The obtained rigid CDs@LiCl-PAM exhibits ultralong green phosphorescence with a lifetime of 560 ms in the initial state. After absorbing moisture, it becomes flexible and its phosphorescence switches off. Moreover, the emission of the CDs@LiCl-PAM film depends on the excitation wavelength. This property can potentially used in multicolored luminescence applications and displays. Moreover, multicolor luminescent patterns can be constructed in situ using the water-absorption ability of the obtained thin film and the Förster resonance energy-transfer strategy. The proposed strategy is expected to promote the interdisciplinary development of intelligent information encryption, anti-counterfeiting, and smart flexible display materials.

Comparative analysis of microbial composition and functional characteristics in dental plaque and saliva of oral cancer patients.

BACKGROUND: The oral cavity is home to various ecological niches, each with its own unique microbial composition. Understanding the microbial communities and gene composition in different ecological niches within the oral cavity of oral cancer (OC) patients is crucial for determining how these microbial populations contribute to disease progression. METHODS: In this study, saliva and dental plaque samples were collected from patients with OC. Metagenomic sequencing was employed to analyze the microbial community classification and functional composition of the different sample groups. RESULTS: The results of the study revealed significant differences in both the function and classification of microbial communities between saliva and dental plaque samples. The diversity of microbial species in saliva was found to be higher compared to  that in plaque samples. Notably, Actinobacteria were enriched in the dental plaque of OC patients. Furthermore, the study identified several inter-group differential marker species, including Prevotella intermedia, Haemophilus parahaemolyticus, Actinomyces radius, Corynebacterium matruchitii, and Veillonella atypica. Additionally, 1,353 differential genes were annotated into 23 functional pathways. Interestingly, a significant correlation was observed between differentially labeled species and Herpes simplex virus 1 (HSV-1) infection, which may be related to the occurrence and development of cancer. CONCLUSIONS: Significant differences in the microbial and genetic composition of saliva and dental plaque samples were observed in OC patients. Furthermore, pathogenic bacteria associated with oral diseases were predominantly enriched in saliva. The identification of inter-group differential biomarkers and pathways provide insights into the relationship between oral microbiota and the occurrence and development of OC.

Nrf2/PINK1-mediated mitophagy induction alleviates sodium fluoride-induced hepatic injury by improving mitochondrial function, oxidative stress, and inflammation.

Mitophagy has distinct functions, which can lead to either protection or damage of tissues. Though current evidence indicated that NaF triggers mitophagy, the role and regulation of mitophagy in sodium fluoride (NaF)-induced liver injury still remain unclear. Therefore, we exployed the cell and mouse models and confirmed that NaF treatment activates mitophagy. Knocking down PTEN-induced putative kinase protein 1 (PINK1) expression attenuated mitophagy and increased the degree of mitochondrial impairment, oxidative stress, and apoptosis in NaF-treated HepG2 cells. In vivo experiments indicated that PINK1 deficiency weakened NaF-induced mitophagy. Moreover, PINK1-deficient mices aggravated NaF-induced hepatic mitochondrial injury, oxidative stress, and inflammation in livers, evidenced by the increased number of abnormal mitochondria, decreased adenosine triphosphate (ATP) and glutathione (GSH) levels, elevated reactive oxygen species (ROS) and malondialdehyde (MDA) content, enhanced hepatic macrophage infiltration and inflammatory cytokine levels. Notably, NaF exposure activated Nrf2 signaling both in vitro and in vivo. Nrf2 siRNA transfection blocked the upregulation of PINK1 expression and the induction of mitophagy in NaF-treated HepG2 cells. Also, ML385 (Nrf2 inhibitor) partially blocked the upregulation of PINK1 expression caused by NaF in mice livers. To sum up, the present study provided the demonstration that Nrf2/PINK1-mediated mitophagy activation offers a hepatoprotective effect by inhibiting NaF-induced mitochondrial dysfunction, oxidative stress, and inflammation.

Fabrication of sulphonated poly(ethylene glycol)-diacrylate hydrogel as a bone grafting scaffold.

To improve the biological performance of poly(ethylene glycol)-diacrylate (PEGDA) hydrogel as an injectable bone grafting scaffold, sodium methallyl sulphonate (SMAS) was incorporated into PEGDA hydrogel. The physiochemical properties of the resultant polymers were assessed via Fourier transform infrared spectroscopy (FTIR), swelling ratio, zeta potential, surface morphology, and protein adsorption analysis. MC3T3-E1 cells were seeded on the hydrogel to evaluate the effect of the sulphonated modification on their attachment, proliferation, and differentiation. The results of FTIR and zeta potential evaluations revealed that SMAS was successfully incorporated into PEGDA. With increasing concentrations of SMAS, the swelling ratio of the hydrogels increased in deionized water but stayed constant in phosphate buffered saline. The protein adsorption also increased with increasing concentration of SMAS. Moreover, the sulphonated modification of PEGDA hydrogel not only enhanced the attachment and proliferation of osteoblast-like MC3T3-E1 cells but also up-regulated alkaline phosphatase activity as well as gene expression of osteogenic markers and related growth factors, including collagen type I, osteocalcin, runt related transcription factor 2, bone morphogenetic protein 2, and transforming growth factor beta 1. These findings indicate that the sulphonated modification could significantly improve the biological performance of PEGDA hydrogel. Thus, the sulphonated PEGDA is a promising scaffold candidate for bone grafting.

Hollow Nanospheres Array Fabrication via Nano-Conglutination Technology.

Hollow nanospheres array is a special nanostructure with great applications in photonics, electronics and biochemistry. The nanofabrication technique with high resolution is crucial to nanosciences and nano-technology. This paper presents a novel nonconventional nano-conglutination technology combining polystyrenes spheres (PSs) self-assembly, conglutination and a lift-off process to fabricate the hollow nanospheres array with nanoholes. A self-assembly monolayer of PSs was stuck off from the quartz wafer by the thiol-ene adhesive material, and then the PSs was removed via a lift-off process and the hollow nanospheres embedded into the thiol-ene substrate was obtained. Thiolene polymer is a UV-curable material via "click chemistry" reaction at ambient conditions without the oxygen inhibition, which has excellent chemical and physical properties to be attractive as the adhesive material in nano-conglutination technology. Using the technique, a hollow nanospheres array with the nanoholes at the diameter of 200 nm embedded into the rigid thiol-ene substrate was fabricated, which has great potential to serve as a reaction container, catalyst and surface enhanced Raman scattering substrate.

Anti-BCMA CAR-T therapy for multiple myeloma with extramedullary disease: A case report and review of the literature.

INTRODUCTION: Multiple myeloma (MM) with extramedullary disease (EMD) is rare in clinical practice, and B cell maturation antigen (BCMA) CAR-T cell therapy is a novel therapy for hematologic malignancies. Very few reports have been published on the effect of CAR-T-cell therapy in MM with EMD. Here, we report a case of MM with extramedullary lesions treated with BCMA CAR-T therapy. CASE PRESENTATION: A 66-year-old female patient presented to our hospital with an enlarged left maxillary gingiva. DIAGNOSIS: Diagnosis of indolent MM stage III (DS staging) and stage III (ISS and R ISS) with extramedullary lesions. INTERVENTION: The patient underwent a clinical trial of humanized anti-BCMA CAR T cell therapy. RESULTS: Symptoms improved; left gingival hyperplasia and swelling resolved; left buccal mass resolved; and neck and submandibular masses resolved. Pathological examination of the exfoliated masses showed necrotic tissue. CONCLUSION: MM with extramedullary lesions often has limited treatment options, and traditional chemotherapy methods are ineffective; however, BCMA CAR-T cell therapy can significantly improve the symptoms of extramedullary lesions in MM.

Multifunctional polydopamine/hemin-cyclodextrin reinforced chitosan nanocomposite hydrogel: A synergistic platform for wound healing.

Chronic cutaneous wounds present a significant challenge for healthcare providers globally, with the risk of bacterial infections emerging as a particularly concerning issue. There is an increasing need to employ a combination of diverse antibacterial strategies to address infections comprehensively in chronic wounds. This study introduces a highly efficient antibacterial platform that encapsulates the NO precursor (BNN6) into ß-cyclodextrin-modified hemin-bearing polydopamine nanoparticles called NO/CHPDA. These nanoparticles are seamlessly integrated into a hydrogel composite comprised of L-arginine grafted chitosan (Arg-CS) and oxide dextrans (oDex). The amalgamation of photothermal therapy (PTT), chemodynamic therapy (CDT), and nitric oxide (NO) antibacterial strategies within the NO/CHPDA@Arg-CS/oDex nanocomposite hydrogel demonstrates a synergistic and highly effective capacity to eradicate bacteria and accelerate the wound healing process in vivo. Remarkably, this nanocomposite hydrogel maintains excellent biocompatibility and induces minimal side effects. The resulting nanocomposite hydrogel represents a promising therapeutic solution for treating bacterial infections in wound healing applications.

Enrichment of steroid hormones in water with porous and hydrophobic polymer-based SPE followed by HPLC-UV determination.

There have been great concerns about the persistence of steroid hormones in surface water. Since the concentrations of these compounds in water samples are usually at a trace level, the efficient enrichment of steroid hormones is vital for further analysis. In this work, a porous and hydrophobic polymer was synthesized and characterized. The composition of solvent used as porogen in the synthetic process was shown to have an effect on the morphology of the polymer, which was successfully used as an SPE sorbent for simultaneously enriching steroid hormones in surface water samples. The recoveries of the steroid hormones on the custom-made polymer ranged from 93.4 to 106.2%, whereas those on commercialized ENVI-18, LC-18, and Oasis HLB ranged from 54.8 to 104.9, 66 to 93.6, and 77.2 to 106%, respectively. Five types of steroid hormones were simultaneously measured using HPLC-UV after they were enriched by the custom-made sorbent. Based on these findings, the SPE-HPLC method was developed. The LODs of this method for estriol, estradiol, estrone, androstenedione, progesterone were 0.07, 0.43, 0.61, 0.27, and 0.42 µg/L, respectively, while precision and reproducibility RSDs were <6.40 and 7.49%, respectively.

Urinary Exosomes: A Promising Biomarker for Disease Diagnosis.

Exosomes are nanoscale vesicles derived from endocytosis, formed by fusion of multivesicular bodies with membranes and secreted into the extracellular matrix or body fluids. Many studies have shown that exosomes can be present in a variety of biological fluids, such as plasma, urine, saliva, amniotic fluid, ascites, and sweat, and most types of cells can secrete exosomes. Exosomes play an important role in many aspects of human development, including immunity, cardiovascular diseases, neurodegenerative diseases, and neoplasia. Urine can be an alternative to blood or tissue samples as a potential source of disease biomarkers because of its simple, noninvasive, sufficient, and stable characteristics. Therefore, urinary exosomes have valuable potential for early screening, monitoring disease progression, prognosis, and treatment. The method for isolating urinary exosomes has been perfected, and exosome proteomics is widely used. Therefore, we review the potential use of urinary exosomes for disease diagnosis and summarize the related literature.

[Study on digital models of normal deciduous dentition in 189 children from Shanghai].

PURPOSE: To study the gender difference and the regulation of growth and development in normal deciduous dentition． METHODS: A total of 189 children with normal deciduous dentition aged 3 to 6 years in several kindergartens in Xuhui District in Shanghai were selected. The three-dimensional(3D) digital dental models were reconstructed by intraoral scanning. Geomagic Studio, a 3D reverse engineering software, was employed to extract the data, such as the dental arc perimeter of C(APC), the dental arc perimeter of E(APE), the dental arc length of C(LC), the dental arc length of E(LE), the dental arc width of C(C-C), the dental arc width of E(E-E), the mesiodistal width of the deciduous crown, the maxillary and mandibular space. SPSS 22.0 software package was used for data analysis. RESULTS: Parameters of deciduous dentition in boys were significantly elevated than in girls(P＜0.05). All the boys and girls were divided into 4 groups by age. In 3-year-old group, significant differences were observed in maxillary APC, C-C, E-E(P＜0.05) between boys and girls. In 4-year-old group, all boys' parameters were significantly greater than girls'(P＜0.05) except maxillary LC. In 5-year-old group, there were significant differences in all the parameters between boys and girl(P＜0.05) except maxillary APE and mandibular APC, LC, LE, C-C. No significant difference was observed in all the parameters except mandibular APE in 6-year old group. The significant difference between boys and girls were observed in the mesiodistal width of each deciduous crown except that of the maxillary lateral incisor and mandibular central incisor (P＜0.05). There were significant differences in maxillary LE and E-E among children of different ages(P＜0.05).The maxillary space was significantly greater than the mandibular space(P＜0.01). CONCLUSIONS: There was gender difference in children's normal deciduous dentition, especially when they were 4 years old.

Multifunctional chitosan/alginate hydrogel incorporated with bioactive glass nanocomposites enabling photothermal and nitric oxide release activities for bacteria-infected wound healing.

It is highly desirable to develop novel multifunctional wound dressing materials capable of delivering active molecules capable of resolving bacterial infections and replenishment of appropriate growth factors for bacteria-infected wound healing. Polysaccharides have numerous biomedical benefits and have been widely used to construct biomaterial scaffolds. Herein, multifunctional chitosan/alginate hydrogel decorated with ß-cyclodextrin (ß-CD) modified polydopamine (PDA)-bioactive glass (BG) nanoparticles (NPs) integrating photothermal performance and nitric-oxide release activities for the treatment of bacterially infected wounds is presented. As the NO precursor N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN6) encapsulated into the hydrophobic cavity of ß-CD on the PDA-coated BG NPs, the resultant NO@CD-PDA/BG NPs, are imparted with the feature of NIR triggered NO release and desired PTT/NO synergetic antibacterial effects. Furthermore, the release of NO, Ca, and Si ions from the NO@CD-PDA/BG NPs, has the benefit of regulating inflammation, promoting fibroblast proliferation, and stimulating angiogenesis. Besides, the chitosan/alginate hydrogel scaffolds provided a suitable microenvironment to accelerate wound healing. By applying the multifunctional chitosan/alginate nanocomposite hydrogel to S. aureus-infected full-thickness skin defect mouse model, the authors demonstrated that chitosan/alginate nanocomposite hydrogel has multiple functions in preventing bacterial infections, accelerating angiogenesis and wound regeneration, indicating promising application in wound healing.

The structure and properties of lignin isolated from various lignocellulosic biomass by different treatment processes.

The structure and properties of lignin can vary depending on the type of lignocellulosic biomass it comes from and the separation techniques used, and also affects its suitability for different applications. In this work, the structure and properties of lignin isolated from moso bamboo, wheat straw, and poplar wood by different treatment processes were compared. Results show that deep eutectic solvent (DES) extracted lignin exhibits well-preserved structures (including ß-O-4, ß-ß, and ß-5 linkages), a low molecular weight (Mn = 2300-3200 g/mol), and relatively homogeneous lignin fragments (1.93 < PDI < 2.33) compared to dealkaline lignin (DL) and milled wood lignin (MWL). Besides, lignin samples extracted by DES have a regular nanostructure, higher carbon residue content (>40 %), and excellent antioxidant properties (the free radical scavenging index >20). Among the three types of biomass, the structural destruction of lignin in straw is the most obvious, which is due to the degradation of ß-O-4 and ß-ß linkages during DES treatment. These findings can contribute to a better understanding of the structural changes that occur in various treatment processes from different lignocellulosic biomass, and help maximize the targeted development of their applications based on the characteristics of lignin.

Effects of microplastics on the growth, photosynthetic efficiency and nutrient composition in freshwater algae Chlorella vulgaris Beij.

Microplastics, plastic particles and fragments smaller than 5 mm are ubiquitous in various aquatic environments, but the hazards of microplastics with different particle sizes, concentrations and materials are not well understood. This study investigated the toxicity of polyethylene microplastics (PE-MPs) with different concentrations and particle sizes or polystyrene microplastics (PS-MPs) on freshwater algae Chlorella vulgaris Beij (C. vulgaris) for 11 days. Results indicated that the growth, colony formation, photosynthetic pigment contents and soluble intracellular polysaccharides were unaffected, whereas the photosynthetic efficiency and the total soluble protein (TSP) contents were remarkably decreased at 11 d with the increased concentration of PE-MP exposure. The growth, photosynthetic efficiency, soluble intracellular polysaccharides and TSP contents were unaffected after exposure to PE-MPs with different particle sizes or PS-MPs. By contrast, the colony formation and photosynthetic pigment contents were remarkably decreased after exposure to PS-MPs compared with the control or PE-MPs with the same particle size. The C. vulgaris colonization on microplastics was proven by scanning electron microscopy, indicating that the adsorption effects were the main harmful pathways of different microplastics to algal. Our results suggested that microplastics have limited harmful effects on algae, mainly in adsorption and shading.

Multistage treatment of bamboo powder waste biomass: Highly efficient and selective isolation of lignin components.

Bamboo pulp and papermaking produce a lot of bamboo powder waste, and its resource utilization is of great significance for biomass refining and environmental protection. Here, we propose an integrated approach involving mechanical activation, hydrothermal extraction, and deep eutectic solvents (DESs) multiple delignification for the efficient separation of bamboo powder. Among seven carboxylic acids based DESs, choline chloride (ChCl)-lactic acid (La) DES (1:1) is the most effective, with over 78.0% lignin removal and 88.9% cellulose retained after mechanical-hydrothermal (180 °C, 5 h)-DES (110 °C, 12 h) treatment. Notably, 84.7% of delignification is achieved after three times of ChCl-La DES treatment at 70, 90, and 110 °C respectively. The delignification rate is negatively correlated with the amount of carboxyl group in the DESs. The lower the pKa value, the higher the delignification rate. Additionally, the selectivity for lignin is improved with decreasing solvent polarity. DES treatment effectively degrades the guaiacyl unit lignin fractions and disrupts several ß-aryl-ether bonds (e.g., ß-O-4, ß-ß, and ß-5). Furthermore, DESs exhibit good recyclability, with less than 10% reduction in delignification after three cycles. Theory calculations confirm that ChCl-carboxylic acid DESs could compete with lignin to break hydrogen bonds in lignocellulosic biomass by providing their chloride, hydroxyl, and carboxyl groups. Overall, this study demonstrates the practical significance of multistage treatment for the effective fractionation of biomass into its three components.

Recyclable nanoparticles based on a boronic acid-diol complex for the real-time monitoring of imprinting, molecular recognition and copper ion detection.

Molecularly imprinted polymers (MIPs) have now become one of the most remarkable materials in the field of molecular recognition. Although many efforts have been made to study the process and mechanism of molecular imprinting, it has not been possible to monitor the interactions between the template and the growing polymer chains under real-time experimental conditions. The behavior of the template-monomer complex during the whole polymerization process has remained largely unknown. In this work, we introduce a fluorescence technique that allows monitoring of the template-functional monomer complex during an actual imprinting process, as well as the real-time signaling of template binding and dissociation from the imprinted polymer. For the first proof-of-principle, we select Alizarin Red S (ARS) and 4-vinylphenylboronic acid as the template and functional monomer, respectively, to synthesize MIP particles via precipitation polymerization. As the formation of the template-functional monomer complex leads to strong fluorescence emission, it allows the status of the template binding to be monitored throughout the whole reaction process in real time. Using the same fluorescence technique, the kinetics of template binding and dissociation can be studied directly without particle separation. The hydrophilic MIP particles can be used as a scavenger to remove ARS from water. In addition, the MIP particles can be used as a recyclable sensor to detect Cu ions. As the Cu ion forms a stable complex with ARS, it causes ARS to dissociate from the MIP nanoparticles, leading to effective fluorescence quenching. The non-separation analytical method based on fluorescence measurement provides a convenient means to study molecular imprinting reactions and the kinetics of molecular recognition using imprinted polymers. The recyclable nanoparticle sensor allows toxic Cu ions to be detected directly in water in the range of 0.1-100 µM with a recovery of 84-95%.

Synthesis of zwitterionic polymer modified graphene oxide for hydrophilic enrichment of N-glycopeptides from urine of healthy subjects and patients with lung adenocarcinoma.

As one of the most common and important post-translational modifications, protein N-glycosylation plays essential roles in many biological processes and have long been considered closely correlated with the occurrence and progression of multiple diseases. Systematic characterization of these disease-related protein N-glycosylation is one of the most convenient ways for new diagnostic biomarker and therapeutic drug target discovering. However, the biological samples are extremely complex and the abundance of N-glycoproteins are especially low, which make highly efficient N-glycoprotein/glycopeptide enrichment before mass spectrometry analysis a prerequisite. In this work, a new type of hydrophilic material (GO-pDMAPS) was prepared by in situ growth of linear zwitterionic polymer chains on the surface of GO and it was successfully applied for N-glycopeptide enrichment from human urine. Due to the excellent hydrophilicity and the facilitate interactions between this GO-pDMAPS and the targets, a total of 1426 N-glycosylated sites corresponding to 766 N-glycoproteins as well as 790 N-glycosylation sites corresponding to 470 N-glycoproteins were enriched and identified from urine of healthy subjects and patients with lung adenocarcinoma, respectively. Among which, 27 N-glycoproteins were expressed exclusively and 4 N-glycoproteins were upregulated at least 3 times comparing with the healthy group, demonstrating the tremendous potential of this new hydrophilic material for large scale and in depth N-glycoproteome research.

In Situ Regulation of Microphase Separation-Recognized Circularly Polarized Luminescence via Photoexcitation-Induced Molecular Aggregation.

Circularly polarized luminescence (CPL) has attracted great interest owing to its extensive optical information and chiral structural dependence. However, rationally regulating solid-phase CPL signals remains difficult because of the close packing of molecules in solid-state materials and the lack of structural visualization. In this work, we proposed a microphase-separation-recognized CPL regulation strategy via coassembly of a hexathiobenzene-based luminophore and chiral block copolymer (cBCP) with in situ photocontrollability. As a consequence to the continuous increase in the luminophore-to-cBCP ratio, the CPL signal of the supramolecular system exhibited an increasing trend until a critical point. Then, further increasing the ratio stretched the helical pitch of cBCP, which led to CPL reduction. With the photoexcitation-induced molecular aggregation of the luminophore, which was implemented using in situ photoirradiation, the helical pitch was retracted along with the restoration of the CPL signal. These processes were fully recognized and monitored by the microphase-separated nanomorphological change of the coassembled system, which indicated that such a structural contrast could be an effective method for rationally regulating the supramolecular chiropticity of solid-state materials.

GSH-Responsive Drug Delivery System for Active Therapy and Reducing the Side Effects of Bleomycin.

The application of drug delivery system (DDS) has achieved breakthroughs in many aspects, especially in the field of tumor treatment. In this work, polyethylene glycol (PEG)-modified hollow mesoporous manganese dioxide (HMnO2@PEG) nanoparticles were used to load the anti-tumor drug bleomycin (BLM). When the DDS reached the tumor site, HMnO2@PEG was degraded and reduced to Mn2+ by the overexpression of glutathione in the tumor microenvironment, and the drug was released simultaneously. BLM coordinated with Mn2+ in situ, thereby greatly improving the therapeutic activity of BLM. The results of in vivo and in vitro treatment experiments showed that the DDS had excellent responsive therapeutic activation ability. In addition, Mn2+ exhibited strong paramagnetism and was used for T1-weighted magnetic resonance imaging in vivo. Furthermore, this therapeutic mode of responsively releasing drugs and activating in situ effectively attenuated pulmonary fibrosis initiated by BLM. In short, this DDS could help in avoiding the side effects of drugs.

Genomic Epidemiology and Phylodynamic Analysis of Enterovirus A71 Reveal Its Transmission Dynamics in Asia.

Enterovirus A71 (EV-A71) is one of the main pathogens causing hand, foot, and mouth disease (HFMD) outbreaks in Asian children under 5 years of age. In severe cases, it can cause neurological complications and be life-threatening. In this study, 200 newly sequenced EV-A71 whole-genome sequences were combined with 772 EV-A71 sequences from GenBank for large-scale analysis to investigate global EV-A71 epidemiology, phylogeny, and Bayesian phylodynamic characteristics. Based on the phylogenetic analysis of the EV-A71 3Dpol region, six new evolutionary lineages (lineages B, J, K, O, P, and Q) were found in this study, and the number of evolutionary lineages was expanded from 11 to 17. Temporal dynamics and recombination breakpoint analyses based on genotype C revealed that recombination of nonstructural protein-coding regions, including 3Dpol, is an important reason for the emergence of new lineages. The EV-A71 epidemic in the Asia-Pacific region is complex, and phylogeographic analysis found that Vietnam played a key role in the spread of subgenotypes B5 and C4. The origin of EV-A71 subgenotype C4 in China is East China, which is closely related to the prevalence of subgenotype C4 in the south and throughout China. Selection pressure analysis revealed that, in addition to VP1 amino acid residues VP1-98 and VP1-145, which are associated with EV-A71 pathogenicity, amino acid residues VP1-184 and VP1-249 were also positively selected, and their functions still need to be determined by biology and immunology. This study aimed to provide a solid theoretical basis for EV-A71-related disease surveillance and prevention, antiviral research, and vaccine development through a comprehensive analysis. IMPORTANCE EV-A71 is one of the most important pathogens causing HFMD outbreaks; however, large-scale studies of EV-A71 genomic epidemiology are currently lacking. In this study, 200 new EV-A71 whole-genome sequences were determined. Combining these with 772 EV-A71 whole-genome sequences in the GenBank database, the evolutionary and transmission characteristics of global and Asian EV-A71 were analyzed. Six new evolutionary lineages were identified in this study. We also found that recombination in nonstructural protein-coding regions, including 3Dpol, is an important cause for the emergence of new lineages. The results provided a solid theoretical basis for EV-A71-related disease surveillance and prevention, antiviral research, and vaccine development.