Enhanced antigen-specific CD8 T cells contribute to early protection against FMDV through swine DC vaccination.

Foot-and-mouth disease virus (FMDV) remains a challenge for cloven-hooved animals. The currently licensed FMDV vaccines induce neutralizing antibody (NAb)-mediated protection but show defects in the early protection. Dendritic cell (DC) vaccines have shown great potency in inducing rapid T-cell immunity in humans and mice. Whether DC vaccination could enhance early protection against FMDV has not been elaborately explored in domestic pigs. In this study, we employed DC vaccination as an experimental approach to study the roles of cellular immunity in the early protection against FMDV in pigs. Autologous DCs were differentiated from the periphery blood mononuclear cells of each pig, pulsed with inactivated FMDV (iFMDV-DC) and treated with LPS, and then injected into the original pigs. The cellular immune responses and protective efficacy elicited by the iFMDV-DC were examined by multicolor flow cytometry and tested by FMDV challenge. The results showed that autologous iFMDV-DC immunization induced predominantly FMDV-specific IFN-γ-producing CD4+ T cells and cytotoxic CD8+ T cells (CTLs), high NAb titers, compared to the inactivated FMDV vaccine, and accelerated the development of memory CD4 and CD8 T cells, which was concomitantly associated with early protection against FMDV virulent strain in pigs. Such early protection was associated with the rapid proliferation of secondary T-cell response after challenge and significantly contributed by secondary CD8 effector memory T cells. These results demonstrated that rapid induction of cellular immunity through DC immunization is important for improving early protection against FMDV. Enhancing cytotoxic CD8+ T cells may facilitate the development of more effective FMDV vaccines.IMPORTANCEAlthough the currently licensed FMDV vaccines provide NAb-mediated protection, they have defects in early immune protection, especially in pigs. In this study, we demonstrated that autologous swine DC immunization augmented the cellular immune response and induced an early protective response against FMDV in pigs. This approach induced predominantly FMDV-specific IFN-γ-producing CD4+ T cells and cytotoxic CD8+ T cells, high NAb titers, and rapid development of memory CD4 and CD8 T cells. Importantly, the early protection conferred by this DC immunization is more associated with secondary CD8+ T response rather than NAbs. Our findings highlighted the importance of enhancing cytotoxic CD8+ T cells in early protection to FMDV in addition to Th1 response and identifying a strategy or adjuvant comparable to the DC vaccine might be a future direction for improving the current FMDV vaccines.

Foot-and-mouth disease virus downregulates vacuolar protein sorting 28 to promote viral replication.

Vacuolar protein sorting 28 (Vps28), a component of the ESCRT-I (endosomal sorting complex required for transport I), plays an important role in the pathogen life cycle. Here, we investigated the reciprocal regulation between Vps28 and the foot-and-mouth disease virus (FMDV). Overexpression of Vps28 decreased FMDV replication. On the contrary, the knockdown of Vps28 increased viral replication. Subsequently, the mechanistic study showed that Vps28 destabilized the replication complex (RC) by associating with 3A rather than 2C protein. In addition, Vps28 targeted FMDV VP0, VP1, and VP3 for degradation to inhibit viral replication. To counteract this, FMDV utilized tactics to restrict Vps28 to promote viral replication. FMDV degraded Vps28 mainly through the ubiquitin-proteasome pathway. Additional data demonstrated that 2B and 3A proteins recruited E3 ubiquitin ligase tripartite motif-containing protein 21 to degrade Vps28 at Lys58 and Lys25, respectively, and FMDV 3Cpro degraded Vps28 through autophagy and its protease activity. Meantime, the 3Cpro-mediated Vps28 degradation principally alleviated the ability to inhibit viral propagation. Intriguingly, we also demonstrated that the N-terminal and C-terminal domains of Vps28 were responsible for the suppression of FMDV replication, which suggested the elaborated counteraction between FMDV and Vps28. Collectively, our results first investigate the role of ESCRTs in host defense against picornavirus and unveil underlying strategies utilized by FMDV to evade degradation machinery for triumphant propagation. IMPORTANCE ESCRT machinery plays positive roles in virus entry, replication, and budding. However, little has been reported on its negative regulation effects during viral infection. Here, we uncovered the novel roles of ESCRT-I subunit Vps28 on FMDV replication. The data indicated that Vps28 destabilized the RC and impaired viral structural proteins VP0, VP1, and VP3 to inhibit viral replication. To counteract this, FMDV hijacked intracellular protein degradation pathways to downregulate Vps28 expression and thus promoted viral replication. Our findings provide insights into how ESCRT regulates pathogen life cycles and elucidate additional information regarding FMDV counteraction of host antiviral activity.

Intracellular Gelation-Mediated Living Bacteria for Advanced Biotherapeutics in Mouse Models.

Despite its significant potential in various disease treatments and diagnostics, microbiotherapy is consistently plagued by multiple limitations ranging from manufacturing challenges to in vivo functionality. Inspired by the strategy involving nonproliferating yet metabolically active microorganisms, we report an intracellular gelation approach that can generate a synthetic polymer network within bacterial cells to solve these challenges. Specifically, poly(ethylene glycol dimethacrylate) (PEGDA, 700 Da) monomers are introduced into the bacterial cytosol through a single cycle of freeze-thawing followed by the initiation of intracellular free radical polymerization by UV light to create a macromolecular PEGDA gel within the bacterial cytosol. The molecular crowding resulting from intracytoplasmic gelation prohibits bacterial division and confers robust resistance to simulated gastrointestinal fluids and bile acids while retaining the ability to secrete functional proteins. Biocompatibility assessments demonstrate that the nondividing gelatinized bacteria are effective in alleviating systemic inflammation triggered by intravenous Escherichia coli injection. Furthermore, the therapeutic efficacy of gelatinized Lactobacillus rhamnosus in colitis mice provides additional support for this approach. Collectively, intracellular gelation indicates a universal strategy to manufacture next-generation live biotherapeutics for advanced microbiotherapy.

Linkages among stem xylem transport, biomechanics, and storage in lianas and trees across three contrasting environments.

PREMISE: Stem xylem transports water and nutrients, mechanically supports aboveground tissues, and stores water and nonstructural carbohydrates. These three functions are associated with three types of cells-vessel, fiber, and parenchyma, respectively. METHODS: We measured stem theoretical hydraulic conductivity (Kt), modulus of elasticity (MOE), tissue water content, starch, soluble sugars, cellulose, and xylem anatomical traits in 15 liana and 16 tree species across three contrasting sites in Southwest China. RESULTS: Lianas had higher hydraulic efficiency and tissue water content, but lower MOE and cellulose than trees. Storage traits (starch and soluble sugars) did not significantly differ between lianas and trees, and trait variation was explained mainly by site, highlighting how environment shapes plant storage strategies. Kt was significantly positively correlated with vessel diameter and vessel area fraction in lianas and all species combined. The MOE was significantly positively correlated with fiber area fraction, wood density, and cellulose in lianas and across all species. The tissue water content was significantly associated with parenchyma area fraction in lianas. Support function was strongly linked with transport and storage functions in lianas. In trees, transport and support functions were not correlated, while storage function was tightly linked with transport and support functions. CONCLUSIONS: These findings enhance our understanding of the relationship between stem xylem structure and function in lianas and trees, providing valuable insights into how plants adapt to environmental changes and the distinct ecological strategies employed by lianas and by trees to balance the demands of hydraulic transport, mechanical support, and storage.

Factors influencing speech improvement following maxillary complete-arch implant-supported restorations: A retrospective study.

OBJECTIVE: This study explored factors affecting speech improvement in patients with an edentulous maxilla after the delivery of a complete-arch implant-supported fixed dental prosthesis (IFDP). MATERIALS AND METHODS: Patients who had received IFDP for edentulous maxilla were enrolled, and various potential speech improvement-related factors were considered, including patient demographics, anterior residual bone volume, preoperative facial features, preoperative acoustic parameters, and adaptation time. Acoustic analysis and perceptual ratings were used to assess three fricatives [s], [f], and [ɕ]. Correlation and regression analyses were conducted to assess the association between changes in fricatives and potential factors (α = .05). RESULTS: The study included 50 patients (18 females and 32 males, aged 50.62 ± 15.71 years, range 19-76). Significant correlations were found among the change in the center of gravity (ΔCoG) of [s] and anterior residual bone volume, zygomatic implants number and proportion (p < .05). These correlations were largely mirrored in the perceptual score (ΔPS) changes. After controlling for age, sex, preoperative acoustic parameters, and adaptation time, the ΔCoG and ΔPS of fricatives were mainly correlated with the anterior residual bone volume, preoperative acoustic parameters, and adaptation time. CONCLUSION: Speech improvements post-IFDP delivery are mainly related to preoperative speech characteristics, anterior residual bone volume, and adaptation time. The residual bone volume's impact on consonants varies with specific articulatory gestures. This study provides insights into forecasting speech outcomes following IFDP restoration and provides recommendations and methods for data collection in developing future prediction models.

Inverted Internal Limiting Membrane Flap Coverage With Autologous Blood Technique After Air-Fluid Exchange and Silicone Oil Tamponade for Extensive Macular Hole Retinal Detachment in Highly Myopic Eyes.

PURPOSE: To report a technique consisting of inverted internal limiting membrane (ILM) flap coverage with autologous blood after air-fluid exchange and silicone oil tamponade in treating extensive retinal detachment secondary to a myopic macular hole (MH). METHODS: This was a retrospective case series. 18 eyes with MHRD extending beyond the equator were included in this study with a minimum follow-up of 6 months. The procedures for pars plan vitrectomy (PPV) included the following: 1) The ILM was peeled to the superior and inferior arcade margins and, except for the ILM in the temporal region, was hinged toward the edge of the MH. 2) Air-fluid exchange was then performed to drain the subretinal fluid through the MH with a flute needle, ensuring that a small amount of subretinal fluid remained to facilitate ILM flap inversion. 3) The ILM flap was used to cover the MH with the assistance of autologous blood. RESULTS: Six months after surgery, the MH was successfully anatomically closed, and retinal reattachment was observed in all 18 eyes of 18 patients. The mean best-corrected visual acuity logarithm of the minimum angle of resolution (logMAR) improved from 2.03 ± 0.61 (ranging from hand motion [2.6] to finger counting [2.3]) to 1.23 ± 0.63 (ranging from hand motion [2.6] to 20/28 [0.15]) ( P < 0.01) at 6 months. CONCLUSION: This surgical technique using an inverted ILM flap combined with autologous blood provides an option for the treatment of extensive MHRD.

Antibacterial and clinical effectiveness of a mouthwash with a novel active system of amine + zinc lactate + fluoride: a randomized controlled trial.

OBJECTIVES: To support the daily oral hygiene of patients experiencing gum inflammation, a new mouthwash was developed containing an amine + zinc lactate + fluoride system. In vitro and clinical efficacy was assessed using traditional methods as well as using novel site-specific and subject-specific analyses of the clinical data. MATERIALS AND METHODS: This mouthwash was evaluated in a 12-h biofilm regrowth assay against a negative control mouthwash and in a 6-month plaque and gingivitis clinical study as compared to a negative control mouthwash. Analyses of healthy versus inflamed sites, visible plaque versus non-visible plaque sites, as well as subject-level evaluations bring new perspectives to the overall performance of this mouthwash and its significance from a patient outcome perspective. RESULTS: Studies demonstrated that this new mouthwash provided long-term (12-h) antibacterial activity after single application in vitro and reduced clinically all plaque and gingivitis parameters after 3 months and 6 months of use when compared to the negative control mouthwash. Examination of site-level and subject-level data determined that this mouthwash significantly increased the number of healthy sites in the oral cavity and significantly improved the gum health of subjects in the study, as compared to the negative control mouthwash. CONCLUSIONS: In vitro and clinical research has demonstrated the antibacterial and clinical benefits of this mouthwash containing an amine compound + zinc lactate + fluoride system. CLINICAL RELEVANCE: Our subject-specific and site-specific analyses provide the dental practitioner with tools that can be used to guide patients who suffer from gingivitis toward optimal product selection and use. CLINICAL TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (reference no. NCT05821712).

Reduced staining from a chlorhexidine mouthwash: A randomized clinical trial.

PURPOSE: To investigate the stain preventing ability of a new chlorhexidine mouthwash while maintaining efficacy using a randomized clinical trial design. METHODS: 98 subjects were enrolled and completed a 4-week clinical study that evaluated the effectiveness of the new mouthwash on plaque, gingivitis, and staining as compared to a commercially available chlorhexidine mouthwash. A subset of 62 subjects was evaluated for the effectiveness of the mouthwashes against plaque bacteria. RESULTS: After 4 weeks of use, the new chlorhexidine mouthwash reduced staining by 42.6% (P< 0.05) as compared to the commercially available mouthwash. The two mouthwashes were equivalent with regards to their effect on gingivitis, plaque, and plaque bacteria. CLINICAL SIGNIFICANCE: A new mouthwash, containing 0.12% chlorhexidine gluconate, has been developed that delivers stain reduction while maintaining equivalent efficacy to a commercially available chlorhexidine mouthwash with regards to gingivitis, plaque, and plaque bacteria. These findings should be considered by dental practitioners when making recommendations to patients whose teeth stain easily and need an anti-gingivitis and anti-plaque mouthwash.

Liquiritin Carbomer Gel Cold Paste Promotes Healing of Solar Dermatitis in Mice.

Ultraviolet radiation (UVR) has various effects on human cells and tissues, which can lead to a variety of skin diseases and cause inconvenience to people's lives. Among them, solar dermatitis is one of the important risk factors for malignant melanoma, so prevention and treatment of solar dermatitis is very necessary. Additionally, liquiritin (LQ) has anti-inflammatory effects. In this study, we aimed to evaluate the anti-inflammatory and pro-wound healing effects of liquiritin carbomer gel cold paste (LQ-CG-CP) in vitro and in vivo. The results of MTT experiments showed no cytotoxicity of LQ at concentrations of 40 µg/mL and below and cell damage at UVB irradiation doses above 60 mJ/cm2. Moreover, LQ can promote cell migration. ELISA results also showed that LQ inhibited the elevation of the inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) after UVB irradiation. In the mouse model of solar dermatitis, 2% LQ-CG-CP showed the best therapeutic efficacy for wound healing and relief of itching compared to MEIBAO moist burn moisturizer (MEBO). What is more, the results of skin histopathological examination show that LQ-CG-CP promotes re-epithelialization, shrinks wounds, and promotes collagen production, thus promoting wound healing. Simultaneously, LQ-CG-CP reduced TNF-α, IL-1ß, and IL-6 expression. In addition, LQ-CG-CP was not observed to cause histopathological changes and blood biochemical abnormalities in mice. Overall, LQ-CG-CP has great potential for the treatment of solar dermatitis.

Core-Shell Au@Nanoplastics as a Quantitative Tracer to Investigate the Bioaccumulation of Nanoplastics in Freshwater Ecosystems.

Studies on the adverse effects of nanoplastics (NPs, particle diameter <1000 nm) including physical damage, oxidative stress, impaired cell signaling, altered metabolism, developmental defects, and possible genetic damage have intensified in recent years. However, the analytical detection of NPs is still a bottleneck. To overcome this bottleneck and obtain a reliable and quantitative distribution analysis in complex freshwater ecosystems, an easily applicable NP tracer to simulate their fate and behavior is needed. Here, size- and surface charge-tunable core-shell Au@Nanoplastics (Au@NPs) were synthesized to study the environmental fate of NPs in an artificial freshwater system. The Au core enables the quantitative detection of NPs, while the polystyrene shell exhibits NP properties. The Au@NPs showed excellent resistance to environmental factors (e.g., 1% hydrogen peroxide solution, simulating gastric fluid, acids, and alkalis) and high recovery rates (>80%) from seawater, lake water, sewage, waste sludge, soil, and sediment. Both positively and negatively charged NPs significantly inhibited the growth of duckweed (Lemna minor L.) but had little effect on the growth of cyanobacteria (Microcystis aeruginosa). In addition, the accumulation of positively and negatively charged NPs in cyanobacteria occurred in a concentration-dependent manner, with positively charged NPs more easily taken up by cyanobacteria. In contrast, negatively charged NPs were more readily internalized in duckweed. This study developed a model using a core-shell Au@NP tracer to study the environmental fate and behavior of NPs in various complex environmental systems.

Atmospheric Water Harvesting by Large-Scale Radiative Cooling Cellulose-Based Fabric.

Atmospheric water harvesting (AWH) has received tremendous interest because of population growth, limited freshwater resources, and water pollution. However, key challenges remain in developing efficient, flexible, and lightweight AWH materials with scalability. Here, we demonstrated a radiative cooling fabric for AWH via its hierarchically structured cellulose network and hybrid sorption-dewing mechanisms. With 8.3% solar absorption and ∼0.9 infrared (IR) emissivity, the material can drop up to 7.5 °C below ambient temperature without energy consumption via radiative cooling. Water adsorption onto the hydrophilic functional groups of cellulose is dominated by sorption at low relative humidity (RH) and dewing at high RH. The cellulose network provides desirable mechanical properties with entangled high-aspect-ratio fibers over tens of adsorption-extraction cycles. In the field test, the cellulose sample exhibited water uptake of 1.29 kg/kg at 80% RH during the night. The profusion of radiative cooling fabric features desirable cost effectiveness and allows fast deployment into large-scale AWH applications.

Integrating a mouth opening assessment of virtual patients to prevent intraoperative challenges during treatment.

Template-guided implant surgery in the posterior region or zygomatic implant surgery using dynamic navigation systems is often hindered if a patient has limited mouth opening. To overcome the problem, the authors have proposed a novel digital protocol that integrates the use of a facial scan for the assessment of the maximal mouth opening of a virtual patient to assist in preoperative planning, thereby minimizing the likelihood of intraoperative obstruction of the surgical site. The proposed method is cost effective and can be easily used in clinical practice.

Articulation distortion in Mandarin-speaking individuals with complete arch maxillary implant-supported fixed dental prostheses.

STATEMENT OF PROBLEM: Implant-supported fixed dental prostheses (IFPs) have been increasingly used to restore edentulous jaws, yet few studies have utilized acoustic analysis for objective evaluation of postrestoration speech outcomes. PURPOSE: The purpose of this clinical study was to assess speech articulation in edentulous individuals before and after the provision of IFPs by combining the results of subjective evaluations and objective acoustic analysis parameters. MATERIAL AND METHODS: The study included thirty-four individuals who had an edentulous maxilla and had been provided with an IFP for over 6 months, along with 6 dentate controls. Acoustic analysis was conducted, and mean opinion scores (MOS) were rated from recordings. The participants were interviewed about perceived speech changes. Changes in the parameters were evaluated using the paired t test or Wilcoxon signed-rank test (α=.05). A comparison between dentate controls and edentulous individuals (with or without prostheses) was made using an independent t test or Mann-Whitney U test (α=.025). RESULTS: Following restoration, the center of gravity (CoG) changes occurred in 11 of 12 consonants in edentulous individuals (P<.05). Prosthesis use allowed the CoG of all affricates and fricatives to appear larger and closer to control values. Before restoration, the CoG of 9 of 12 consonants in edentulous individuals differed from controls (P<.01); after restoration, this reduced to 3 out of 12 (P<.01). MOS improved in 10 of 12 consonants (P<.01), nearing a score of 4. Despite restoration, the CoG of alveolo-palatals [tɕh], [tɕ], and [ɕ] remained different from controls (P<.01). Most participants were satisfied with the improvement, with few reporting discomfort with alveolars [s] and [tsh]. CONCLUSIONS: IFPs can enhance speech in edentulous individuals, yet articulation distortions of alveolar and alveolo-palatal consonants persist. The improper palatal shape of IFPs or an abrupt joint between the IFP and atrophic natural bone may contribute to these distortions.

Assessment of early dental arch growth modification with removable maxillary expansion by cone-beam computed tomography and lateral cephalometric radiographs: a retrospective study.

BACKGROUND: This study evaluated the skeletal and dental changes of patients brought by early removable maxillary expansion (ERME) treatment to explore the clinical treatment effect of ERME on early dental arch growth modification. METHODS: Subject children aged 6-10 years with a maxillary transverse deficiency received ERME treatment, cone-beam computed tomography (CBCT) and lateral cephalometric radiographs were measured before and after treatment, and statistical differences in the measured items were evaluated with corresponding statistical methods to explore the skeletal and dental changes. RESULTS: After ERME treatment, there was a statistical increase in the maxillary basal bone arch width, nasal cavity width, maxillary alveolar bone arch width, and maxillary dental arch width. A buccal inclination of the maxillary alveolar bone and a buccal inclination and buccal movement in the alveolar bone of maxillary first molars were found. The maxillary skeletal expansion was statistically greater than the dental expansion. Increases in the mandibular alveolar bone arch width and dental arch width happened after treatment. A decrease in angle ANB and an increase in Ptm-A, U1-SN, U1-PP, L1-MP, and L6-MP were found after treatment. No statistical changes in the growth pattern-related measured items were observed. CONCLUSIONS: ERME could expand the maxillary basal bone arch width, nasal cavity width, maxillary alveolar bone arch width, and maxillary dental arch width. The maxillary skeletal expansion was greater than the dental expansion. Secondary increases in the mandibular alveolar bone and dental arch widths would happen after ERME. ERME would result in a mandibular advancement, a labial inclination of maxillary anterior teeth, and an increase of maxillary sagittal length, and would not change the patient's growth pattern. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of the West China Hospital of Stomatology, Sichuan University. (WCHSIRB-D-2020-446).

Controllable Synthesis of Web-Footed PdCu Nanosheets and Their Electrocatalytic Applications.

Morphological control of noble-metal-based nanocrystals has attracted enormous attention because their catalytic behaviors can be optimized well by adjusting the size and shape. Herein, the controllable synthesis of web-footed PdCu nanosheets via a facile surfactant-free method is reported. It is discovered that the Cu(II) precursor in this synthetic system displays a critical role in growing branches along the lateral of nanosheets. This work demonstrates a Pd-based alloy nanoarchitecture for efficient and stable electrocatalysis of both ethanal and formic acid oxidation reactions.

Nucleolin Promotes IRES-Driven Translation of Foot-and-Mouth Disease Virus by Supporting the Assembly of Translation Initiation Complexes.

Nucleolin (NCL), a stress-responsive RNA-binding protein, has been implicated in the translation of internal ribosome entry site (IRES)-containing mRNAs, which encode proteins involved in cell proliferation, carcinogenesis, and viral infection (type I IRESs). However, the details of the mechanisms by which NCL participates in IRES-driven translation have not hitherto been described. Here, we identified NCL as a protein that interacts with the IRES of foot-and-mouth disease virus (FMDV), which is a type II IRES. We also mapped the interactive regions within FMDV IRES and NCL in vitro. We found that NCL serves as a substantial regulator of FMDV IRES-driven translation but not of bulk cellular or vesicular stomatitis virus cap-dependent translation. NCL also modulates the translation of and infection by Seneca Valley virus (type III-like IRES) and classical swine fever virus (type III IRES), which suggests that its function is conserved in unrelated IRES-containing viruses. We also show that NCL affects viral replication by directly regulating the production of viral proteins and indirectly regulating FMDV RNA synthesis. Importantly, we observed that the cytoplasmic relocalization of NCL during FMDV infection is a substantial step for viral IRES-driven translation and that NCL specifically promotes the initiation phase of the translation process by recruiting translation initiation complexes to viral IRES. Finally, the functional importance of NCL in FMDV pathogenicity was confirmed in vivo. Taken together, our findings demonstrate a specific function for NCL in selective mRNA translation and identify a target for the development of a broad-spectrum class of antiviral interventions. IMPORTANCE FMDV usurps the cellular translation machinery to initiate viral protein synthesis via a mechanism driven by IRES elements. It allows the virus to shut down bulk cellular translation, while providing an advantage for its own gene expression. With limited coding capacity in its own genome, FMDV has evolved a mechanism to hijack host proteins to promote the recruitment of the host translation machinery, a process that is still not well understood. Here, we identified nucleolin (NCL) as a positive regulator of the IRES-driven translation of FMDV. Our study supports a model in which NCL relocalizes from the nucleus to the cytoplasm during the course of FMDV infection, where the cytoplasmic NCL promotes FMDV IRES-driven translation by bridging the translation initiation complexes with viral IRES. Our study demonstrates a previously uncharacterized role of NCL in the translation initiation of IRES-containing viruses, with important implications for the development of broad antiviral interventions.

A Heat-Induced Mutation on VP1 of Foot-and-Mouth Disease Virus Serotype O Enhanced Capsid Stability and Immunogenicity.

Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting cloven-hoofed animals that causes a significant economic burden globally. Vaccination is the most effective FMD control strategy. However, FMD virus (FMDV) particles are prone to dissociate when appropriate physical or chemical conditions are unavailable, such as an incomplete cold chain. Such degraded vaccines result in compromised herd vaccination. Therefore, thermostable FMD particles are needed for use in vaccines. This study generated thermostable FMDV mutants (M3 and M10) by serial passages at high temperature, subsequent amplification, and purification. Both mutants contained an alanine-to-threonine mutation at position 13 in VP1 (A1013T), although M3 contained 3 additional mutations. The selected mutants showed improved stability and immunogenicity in neutralizing antibody titers, compared with the wild-type (wt) virus. The sequencing analysis and cryo-electron microscopy showed that the mutation of alanine to threonine at the 13th amino acid in the VP1 protein (A1013T) is critical for the capsid stability of FMDV. Virus-like particles containing A1013T (VLPA1013T) also showed significantly improved stability to heat treatment. This study demonstrated that Thr at the 13th amino acid of VP1 could stabilize the capsid of FMDV. Our findings will facilitate the development of a stable vaccine against FMDV serotype O. IMPORTANCE Foot-and-mouth disease (FMD) serotype O is one of the global epidemic serotypes and causes significant economic loss. Vaccination plays a key role in the prevention and control of FMD. However, the success of vaccination mainly depends on the quality of the vaccine. Here, the thermostable FMD virus (FMDV) mutants (M3 and M10) were selected through thermal screening at high temperatures with improved stability and immunogenicity compared with the wild-type virus. The results of multisequence alignment and cryo-electron microscopy (cryo-EM) analysis showed that the Thr substitution at the 13th amino acid in the VP1 protein is critical for the capsid stability of FMDV. For thermolabile type O FMDV, this major discovery will aid the development of its thermostable vaccine.

Progress, Challenge, and Perspective of Fabricating Cellulose.

Cellulose as the most abundant biopolymers on Earth, presents appealing performance in mechanical properties, thermal management, and versatile functionalization. Developing fabrication methods to design functional materials and open new application areas. However, cellulose is hard to be dissolved or melt due to its recalcitrant property. Herein, the recent progress of fabricating cellulose is summarized. First, the unique hierarchical structure of cellulose is fully investigated and the resulted processability is analysed in directions of down to nanocellulose, dissolution, and thermoplastic processing. Then, the reported fabrication methods are summarized in three aspects: (1) self-assembly from nano/micro cellulose suspensions, especially the formation of cellulose nanocrystals; (2) dissolution-regeneration-drying, covering spinning and solvent infusion processing; and (3) thermoplastic processing, focusing on the setup and the morphology changes of the prepared products. In each aspect, the flowchart of the fabrication method, the mechanism, fabricated products, and effects of processing parameters are explored. Finally, this review provides a perspective on the further direction of fabricating cellulose, especially the challenges toward mass production.

A Comparative Study of Bone Tissue Morphology and Bone Turnover Markers in Different Stages of Kümmell's Disease.

Although the incidence of Kümmell's disease (KD) has increased significantly in recent years, its pathological mechanism is still unclear. The aim of this study is to investigate the histomorphological characteristics and the kinetics of bone turnover markers following KD. This study involves 82 patients with KD, and fasting blood samples were collected to detect the serum concentration of bone turnover markers. A transpedicular bone biopsy was performed to collect bone biopsy specimens during vertebroplasty surgery. According to Li's staging system for KD, all cases were divided into 3 stages. Comparisons of the 3 stages and their kinetics were conducted. 19 (23.2%) patients were classified as Stage I, 39 (47.5%) as Stage II, 24 (29.2%) as Stage III. Bone histomorphological analysis showed that the ratios of WBV and FV reached a peak value (14.23 ± 0.62 and 54.63% ± 3.52%; p = 0.001 and 0.001) at Stage I. The ratios of NBV remained low (4.81% ± 2.61%) in Stage I, but reached a peak value (18.50% ± 2.77%; p = 0.001) in Stage III. Bone metabolism index level showed that the serum concentration of OST and ß-CTX continued to rise after fracture, reaching a peak value of (38.15 ± 3.84 and 1.31 ± 0.16 ng/Ml; p = 0.073 and 0.026), while PINP reached its valley value (48.57 ± 7.25 ng/Ml; p = 0.069) in Stage III. A significant and negative correlation was found between the ratio of ß-CTX and EBV/TV (p= 0.0194, r = -0.2037), and FV/TV (p= 0.0001, r = -0.5368). At the same time, ß-CTX had a positive significant correlation with the NBV/TV (p= 0.0001, r = 0.6218). Bone histomorphometric analysis and bone turnover markers showed that KD has a possibility of healing in the early stage.

Nano-titanium nitride causes developmental toxicity in zebrafish through oxidative stress.

Nano-titanium nitride (Nano-TiN) has strong resistance to wear and corrosion, good biocompatibility, and an attractive metallic luster. Nano-TiN is widely used in medical devices, such as orthopedic implants, syringe needles, coronary stents, and long-term dental implants, and also in imitation gold jewelry. Despite its widespread use, there are few reports describing safety evaluations of Nano-TiN. Here, we exposed healthy zebrafish embryos to different concentrations of Nano-TiN solution for five days, starting at about four hours post fertilization, and found that Nano-TiN caused dose- and time-dependent developmental toxicity. With increasing Nano-TiN concentration and length of exposure, mortality, and deformities gradually increased; body length shortened and hatching rate and motility were significantly reduced. We also found that exposure to Nano-TiN affected development of the heart, liver, nerves, and other organs, and led to elevated levels of reactive oxygen species and reduced antioxidant capacity. Exposure to Nano-TiN resulted in downregulation of expression of antioxidant genes, such as nrf2, gclc, gclm, ho-1, and nqo1. Our results showed that exposure to Nano-TiN caused developmental and organ toxicity in zebrafish embryos and that the toxic effects may be mediated through oxidative stress.