Multiple-Site SUMOylation of FMDV 3C Protease and Its Negative Role in Viral Replication.

Protein SUMOylation represents an important cellular process that regulates the activities of numerous host proteins as well as of many invasive viral proteins. Foot-and-mouth disease virus (FMDV) is the first animal virus discovered. However, whether SUMOylation takes place during FMDV infection and what role it plays in FMDV pathogenesis have not been investigated. In the present study, we demonstrated that SUMOylation suppressed FMDV replication by small interfering RNA (siRNA) transfection coupled with pharmaceutical inhibition of SUMOylation, which was further confirmed by increased virus replication for SUMOylation-deficient FMDV with mutations in 3C protease, a target of SUMOylation. Moreover, we provided evidence that four lysine residues, Lys-51, -54, -110, and -159, worked together to confer the SUMOylation to the FMDV 3C protease, which may make SUMOylation of FMDV 3C more stable and improve the host's chance of suppressing the replication of FMDV. This is the first report that four lysine residues can be alternatively modified by SUMOylation. Finally, we showed that SUMOylation attenuated the cleavage ability, the inhibitory effect of the interferon signaling pathway, and the protein stability of FMDV 3C, which appeared to correlate with a decrease in FMDV replication. Taken together, the results of our experiments describe a novel cellular regulatory event that significantly restricts FMDV replication through the SUMOylation of 3C protease. IMPORTANCE FMD is a highly contagious and economically important disease in cloven-hoofed animals. SUMOylation, the covalent linkage of a small ubiquitin-like protein to a variety of substrate proteins, has emerged as an important posttranslational modification that plays multiple roles in diverse biological processes. In this study, four lysine residues of FMDV 3C were found to be alternatively modified by SUMOylation. In addition, we demonstrated that SUMOylation attenuated FMDV 3C function through multiple mechanisms, including cleavage ability, the inhibitory effect of the interferon signaling pathway, and protein stability, which, in turn, resulted in a decrease of FMDV replication. Our findings indicate that SUMOylation of FMDV 3C serves as a host cell defense against FMDV replication. Further understanding of the cellular and molecular mechanisms driving this process should offer novel insights to design an effective strategy to control the dissemination of FMDV in animals.

Inhibition of Antiviral Innate Immunity by Foot-and-Mouth Disease Virus Lpro through Interaction with the N-Terminal Domain of Swine RNase L.

Foot-and-mouth disease virus (FMDV) is the pathogen of foot-and-mouth disease (FMD), which is a highly contagious disease in cloven-hoofed animals. To survive in the host, FMDV has evolved multiple strategies to antagonize host innate immune responses. In this study, we showed that the leader protease (Lpro) of FMDV, a papain-like proteinase, promoted viral replication by evading the antiviral interferon response through counteracting the 2',5'-oligoadenylate synthetase (OAS)/RNase L system. Specifically, we observed that the titers of Lpro deletion virus were significantly lower than those of wild-type FMDV (FMDV-WT) in cultured cells. Our mechanistic studies demonstrated that Lpro interfered with the OAS/RNase L pathway by interacting with the N-terminal domain of swine RNase L (sRNase L). Remarkably, Lpro of FMDV exhibited species-specific binding to RNase L in that the interaction was observed only in swine cells, not human, monkey, or canine cells. Lastly, we presented evidence that by interacting with sRNase L, FMDV Lpro inhibited cellular apoptosis. Taken together, these results demonstrate a novel mechanism that Lpro utilizes to escape the OAS/RNase L-mediated antiviral defense pathway. IMPORTANCE FMDV is a picornavirus that causes a significant disease in agricultural animals. FMDV has developed diverse strategies to escape the host interferon response. Here, we show that Lpro of FMDV antagonizes the OAS/RNase L pathway, an important interferon effector pathway, by interacting with the N-terminal domain of sRNase L. Interestingly, such a virus-host interaction is species-specific because the interaction is detected only in swine cells, not in human, monkey, or canine cells. Furthermore, Lpro inhibits apoptosis through interacting with sRNase L. This study demonstrates a novel mechanism by which FMDV has evolved to inhibit host innate immune responses.

Decellularized ECM derived from normal bone involved in the viability and chemo-sensitivity in multiple myeloma cells.

Multiple myeloma (MM) is an incurable plasma cell malignancy. The progression of MM is closely related to the bone microenvironment. Bone matrix proteins are remodeled and manipulated to govern cancer growth during the process of MM. However the role of normal bone extracellular matrix in MM is still unclear. In this study the decellularized extracellular matrix derived from normal SD rats' skulls (N-dECM) was prepared by decellularization technology. The CCK 8 assay and the dead-live cell kit assay were used to determine the viability of MM cells and the sensitivity to bortezomib. The Realtime PCR and Western blot assay were used to assay the mRNA and protein related to MM. Under the treatment of N-dECM, we found that the viability of MM cells was inhibited and the sensitivity of MM cells to bortezomib was increased. Additionally, the expression levels of APRIL and TACI, which participated in the progression of MM, were significantly decreased in MM cells. It suggested that N-dECM might inhibit the development of MM via APRIL-TACI axis, and our study may provide a novel and potential biomaterial for MM therapy.

Prevalence and Management of Severe Hand, Foot, and Mouth Disease in Xiangyang, China from 2008-2013.

Therapeutic strategies for severe hand, foot, and mouth disease (HFMD) are currently either inconsequent or deficient in evidence. We retrospectively surveyed HFMD outbreaks in Xiangyang from June 2008 to December 2013. HFMD is staged form I to V according to clinical severity and the case with central nervous system involvement is defined as a severe one. We analyzed risk factors for fatality of severe cases and compared the efficiency and outcome of some therapies by binary logistic regression. The overall HFMD cases included 637 (1.26%) severe cases, 38 fatalities (0.75‰). Analysis indicates that age (<3 y), enterovirus 71 (+), autonomic nervous system dysregulation, pulmonary edema/hemorrhage, CRP (>40 mg/L) and cardiac troponin I (>0.04 ng/mL) are risk factors for fatality (all P < 0.05). Intravenous immunoglobulin (IVIG) and mechanical ventilation applied only in early stage IV significantly improved HFMD progression (both P < 0.05) with odds ratios of 0.24 (95% CI: 0.10-0.57) and 0.01 (95% CI: 0.00-0.10), respectively. Neither methylprednisolone nor milrinone administered in any stage made any significant difference on mortality (all P > 0.05). Precise recognition of the severe HFMD cases in early stage IV and prompt IVIG and mechanical ventilation application may decrease mortality. Mechanical ventilation training programs and dispatching specialists to county-level or district hospitals when there is no chance of transfer critical HFMD cases to a superior hospital are two key successful administrative initiatives. This article is protected by copyright. All rights reserved.

Tailoring bacterial cellulose structure through CRISPR interference-mediated downregulation of galU in Komagataeibacter xylinus CGMCC 2955.

Diverse applications of bacterial cellulose (BC) have different requirements in terms of its structural characteristics. culturing Komagataeibacter xylinus CGMCC 2955, BC structure changes with alterations in oxygen tension. Here, the K. xylinus CGMCC 2955 transcriptome was analyzed under different oxygen tensions. Transcriptome and genome analysis indicated that BC structure is related to the rate of BC synthesis and cell growth, and galU is an essential gene that controls the carbon metabolic flux between the BC synthesis pathway and the pentose phosphate (PP) pathway. The CRISPR interference (CRISPRi) system was utilized in K. xylinus CGMCC 2955 to control the expression levels of galU. By overexpressing galU and interfering with different sites of galU sequences using CRISPRi, we obtained strains with varying expression levels of galU (3.20-3014.84%). By testing the characteristics of BC, we found that the porosity of BC (range: 62.99-90.66%) was negative with galU expression levels. However, the crystallinity of BC (range: 56.25-85.99%) was positive with galU expression levels; galU expression levels in engineered strains were lower than those in the control strains. Herein, we propose a new method for regulating the structure of BC to provide a theoretical basis for its application in different fields.

Flexible liposomal gel dual-loaded with all-trans retinoic acid and betamethasone for enhanced therapeutic efficiency of psoriasis.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease without effective treatment. The utilization of all trans-retinoic acid (TRA) and betamethasone (BT) for the treatment of psoriasis is still facing difficulties, due to their relatively poor stability, limited skin permeation, and systemic side effects. Flexible liposomes are excellent in deeper skin permeation and reducing the side effects of drugs, which is promising for effective treatment of skin disorders. This work aimed to establish dual-loaded flexible liposomal gel for enhanced therapeutic efficiency of psoriasis based on TRA and BT. RESULTS: Flexible liposomes co-loaded with TRA and BT were successfully prepared in our study. The characterization examination revealed that flexible liposomes featured nano-sized particles (around 70 nm), high drug encapsulation efficiency (> 98%) and sustained drug release behaviors. Flexible liposomes remarkably increased the drug skin permeation and retention as compared with free drugs. Results on HaCaT cells suggested that flexible liposomes were nontoxic, and its cellular uptake has a time-dependent manner. In vivo studies suggested the topical application of TRA and BT dual-loaded liposomal gel had the best ability to reduce the thickness of epidermal and the level of cytokines (TNF-α and IL-6), largely alleviating the symptoms of psoriasis. CONCLUSIONS: Flexible liposomal gel dual-loaded with TRA and BT exerted a synergistic effect, which is a promising topical therapeutic for the treatment of psoriasis.

Sialic Acid-Functionalized PEG-PLGA Microspheres Loading Mitochondrial-Targeting-Modified Curcumin for Acute Lung Injury Therapy.

Acute lung injury (ALI) is a serious illness without resultful therapeutic methods commonly. Recent studies indicate the importance of oxidative stress in the occurrence and development of ALI, and mitochondria targeted antioxidant has become a difficult and hot topic in the research of ALI. Therefore, a sialic acid (SA)-modified lung-targeted microsphere (MS) for ALI therapy are developed, with triphenylphosphonium cation (TPP)-modified curcumin (Cur-TPP) loaded, which could specifically target the mitochondria, increasing the effect of antioxidant. The results manifest that with the increase of microsphere, lung distribution of microsphere is also increased in murine mice, and after SA modification, the microsphere exhibits the ideal lung-targeted characteristic in ALI model mice, due to SA efficiently targeting to E-selectin expressed on inflammatory tissues. Further investigations indicate that SA/Cur-TPP/MS has better antioxidative capacity, decreases intracellular ROS generation, and increases mitochondrial membrane potential, contributing to a lower apoptosis rate in human umbilical vein endothelial cells (HUVECs) compared to H2O2 group. In vivo efficacy of SA/Cur-TPP/MS demonstrates that the inflammation has been alleviated markedly and the oxidative stress is ameliorated efficiently. Significant histological improvements by SA/Cur-TPP/MS are further proved via HE stains. In conclusion, SA/Cur-TPP/MS might act as a promising drug formulation for ALI therapy.

Preferential binding between intracellular organic matters and Al13 polymer to enhance coagulation performance.

Coagulation is the best available method for removing intracellular organic matter (IOM), which is released from algae cells and is an important precursor to disinfection by-products in drinking water treatment. To gain insight into the best strategy to optimize IOM removal, the coagulation performance of two Al salts, i.e., aluminum chloride (AlCl3) and polyaluminum chloride (PACl, containing 81.2% Al13), was investigated to illuminate the effect of Al species distribution on IOM removal. PACl showed better removal efficiency than AlCl3 with regard to the removal of turbidity and dissolved organic carbon (DOC), owing to the higher charge neutralization effect and greater stability of pre-formed Al13 species. High pressure size exclusion chromatography analysis indicated that the superiority of PACl in DOC removal could be ascribed to the higher binding affinity between Al13 polymer and the low and medium molecular weight (MW) fractions of IOM. The results of differential log-transformed absorbance at 254 and 350 nm indicated more significant formation of complexes between AlCl3 and IOM, which benefits the removal of tryptophan-like proteins thereafter. Additionally, PACl showed more significant superiority compared to AlCl3 in the removal of <5 kDa and hydrophilic fractions, which are widely viewed as the most difficult to remove by coagulation. This study provides insight into the interactions between Al species and IOM, and advances the optimization of coagulation for the removal of IOM in eutrophic water.

Safety and efficacy of 6-month versus 12-month dual antiplatelet therapy in patients after implantation of multiple biodegradable polymer-coated sirolimus-eluting coronary stents: Insight from the I-LOVE-IT 2 trial.

OBJECTIVE: This study sought to compare the clinical outcomes of 6-month versus 12-month dual antiplatelet therapy (DAPT) in patients receiving multiple biodegradable polymer-coated sirolimus-eluting stents (BP-SES) implants. BACKGROUND: The clinical outcomes for patients who undergo multiple BP-SES implantation with different DAPT durations are uncertain. METHODS: In the I-LOVE-IT 2 trial, 907 patients treated with multiple BP-SES (total stent number ≥2) were assigned to receive 6-month (n = 440) or 12-month (n = 467) DAPT. The primary endpoint was 12-month target lesion failure (TLF), which is a composite of cardiac death, target vessel myocardial infarction (MI) or clinically indicated target lesion revascularization. The major secondary endpoints were 12-month net adverse clinical events, a composite of all causes of death, MI, stroke, any revascularization and bleeding. RESULTS: The number of stents per patient between the 6-month and 12-month DAPT group was similar (2.4 ± 0.7 vs. 2.4 ± 0.7, P = 0.47). The incidence of 12-month TLF was comparable in the 6-month and 12-month DAPT groups (9.3% vs.7.5%, Log-rank P = 0.33). However, landmark analysis showed that 12-month DAPT, compared to 6-month DAPT, was associated with a significantly lower risk of TLF (4.8% vs. 2.4%, Log-rank P = 0.049) at a cost of a slightly increased risk of all bleeding events (0.5% vs. 1.7%, Log-rank P = 0.07) between 6 and 12 months. CONCLUSIONS: In patients treated with multiple BP-SES, 6- and 12-month DAPT had similar impacts on 12-month clinical outcomes. Additionally, 12-month DAPT might reduce TLF between 6 and 12 months at the cost of a slightly increased risk of all bleeding events. © 2017 Wiley Periodicals, Inc.

Methods for improving the properties of zinc for the application of biodegradable vascular stents.

Biodegradable stents can support vessels for an extended period, maintain vascular patency, and progressively degrade once vascular remodeling is completed, thereby reducing the constraints of traditional metal stents. An ideal degradable stent must have good mechanical properties, degradation behavior, and biocompatibility. Zinc has become a new type of biodegradable metal after magnesium and iron, owing to its suitable degradation rate and good biocompatibility. However, zinc's poor strength and ductility make it unsuitable as a vascular stent material. Therefore, this paper reviewed the primary methods for improving the overall properties of zinc. By discussing the mechanical properties, degradation behavior, and biocompatibility of various improvement strategies, we found that alloying is the most common, simple, and effective method to improve mechanical properties. Deformation processing can further improve the mechanical properties by changing the microstructures of zinc alloys. Surface modification is an important means to improve the biological activity, blood compatibility and corrosion resistance of zinc alloys. Meanwhile, structural design can not only improve the mechanical properties of the vascular stents, but also endow the stents with special properties such as negative Poisson 's ratio. Manufacturing zinc alloys with excellent degradation properties, improved mechanical properties and strong biocompatibility and exploring their mechanism of interaction with the human body remain areas for future research.

Nanoparticle technology for mRNA: Delivery strategy, clinical application and developmental landscape.

The mRNA vaccine, a groundbreaking advancement in the field of immunology, has garnered international recognition by being awarded the prestigious Nobel Prize, which has emerged as a promising prophylactic and therapeutic modality for various diseases, especially in cancer, rare disease, and infectious disease such as COVID-19, wherein successful mRNA treatment can be achieved by improving the stability of mRNA and introducing a safe and effective delivery system. Nanotechnology-based delivery systems, such as lipid nanoparticles, lipoplexes, polyplexes, lipid-polymer hybrid nanoparticles and others, have attracted great interest and have been explored for mRNA delivery. Nanoscale platforms can protect mRNA from extracellular degradation while promoting endosome escape after endocytosis, hence improving the efficacy. This review provides an overview of diverse nanoplatforms utilized for mRNA delivery in preclinical and clinical stages, including formulation, preparation process, transfection efficiency, and administration route. Furthermore, the market situation and prospects of mRNA vaccines are discussed here.

Precise tooth design using deep learning-based templates.

OBJECTIVES: In prosthodontic procedures, traditional computer-aided design (CAD) is often time-consuming and lacks accuracy in shape restoration. In this study, we combined implicit template and deep learning (DL) to construct a precise neural network for personalized tooth defect restoration. METHODS: Ninety models of right maxillary central incisor (80 for training, 10 for validation) were collected. A DL model named ToothDIT was trained to establish an implicit template and a neural network capable of predicting unique identifications. In the validation stage, teeth in validation set were processed into corner, incisive, and medium defects. The defective teeth were inputted into ToothDIT to predict the unique identification, which actuated the deformation of the implicit template to generate the highly customized template (DIT) for the target tooth. Morphological restorations were executed with templates from template shape library (TSL), average tooth template (ATT), and DIT in Exocad (GmbH, Germany). RMSestimate, width, length, aspect ratio, incisal edge curvature, incisive end retraction, and guiding inclination were introduced to assess the restorative accuracy. Statistical analysis was conducted using two-way ANOVA and paired t-test for overall and detailed differences. RESULTS: DIT displayed significantly smaller RMSestimate than TSL and ATT. In 2D detailed analysis, DIT exhibited significantly less deviations from the natural teeth compared to TSL and ATT. CONCLUSION: The proposed DL model successfully reconstructed the morphology of anterior teeth with various degrees of defects and achieved satisfactory accuracy. This approach provides a more reliable reference for prostheses design, resulting in enhanced accuracy in morphological restoration. CLINICAL SIGNIFICANCE: This DL model holds promise in assisting dentists and technicians in obtaining morphology templates that closely resemble the original shape of the defective teeth. These customized templates serve as a foundation for enhancing the efficiency and precision of digital restorative design for defective teeth.

Trade-off of abiotic stress response in floating macrophytes as affected by nanoplastic enrichment.

Nanoparticles have been found in large-scale environmental media in recent years, causing toxic effects in various organisms and even humans through food chain transmission. The ecotoxicological impact of microplastics on specific organisms is currently receiving much attention. However, relatively little research to date has examined the mechanisms through which nanoplastic residue may exert an interference effect on floating macrophytes in constructed wetlands. In our study, the aquatic plant Eichhornia crassipes was subjected to 100 nm polystyrene nanoplastics at concentrations of 0.1, 1 and 10 mg L-1 after 28 days of exposure. E. crassipes can decrease the concentration of nanoplastics in water by 61.42∼90.81% through phytostabilization. The abiotic stress of nanoplastics on the phenotypic plasticity (morphological and photosynthetic properties and antioxidant systems as well as molecular metabolism) of E. crassipes was assessed. The presence of nanoplastics reduced the biomass (10.66%∼22.05%), and the functional organ (petiole) diameters of E. crassipes decreased by 7.38%. The photosynthetic efficiency was determined, showing that the photosynthetic systems of E. crassipes are very sensitive to stress by nanoplastics at a concentration of 10 mg L-1. Oxidative stress and imbalance of antioxidant systems in functional organs are associated with multiple pressure modes from nanoplastic concentrations. The catalase contents of roots increased by 151.19% in the 10 mg L-1 treatment groups compared with the control group. Moreover, 10 mg L-1 concentrations of the nanoplastic pollutant interfere with purine and lysine metabolism in the root system. The hypoxanthine content was reduced by 6.58∼8.32% under exposure to different concentrations of nanoplastics. In the pentose phosphate pathway, the phosphoric acid content was decreased by 32.70% at 10 mg L-1 PS-NPs. In the pentose phosphate pathway, the phosphoric acid content was decreased by 32.70% at 10 mg L-1 PS-NPs. Nanoplastics disturb the efficiency of water purification by floating macrophytes, which reduces the chemical oxygen demand (COD) removal efficiency (from 73% to 31.33%) due to various abiotic stresses. This study provided important information for further clarifying the impact of nanoplastics on the stress response of floating macrophytes.

Association between periodontal disease and osteoporosis in postmenopausal women: A systematic review and meta-analysis.

Objective: To evaluate the relationship between periodontitis and postmenopausal osteoporosis. Methods: This research was carried out according to the principles laid down by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline statement. We searched the Web of Science, Embase, PubMed, The Cochrane Library, CNKI, VIP, and WanFang databases from inception to July 1, 2023 to collect all relevant publications, with no restrictions on publication date or Languages. Cochrane's tool for assessing RoB was used to evaluate the RoB for RCTs. The Newcastle-Ottawa Scale was used to assess the RoB for cohort studies and case-control studies. Mean differences (MD) with 95 % confidence intervals (CI) were used for analysis of continuous data. Heterogeneity was measured using the I2 statistic. Revman 5.4 software was used for the meta-analysis. Results: 28 observational studies with 19611 patients, including 5813 cases in the postmenopausal osteoporosis group and 13798 cases in the non-osteoporosis group. The studies showed that the degrees of clinical attachment loss (CAL), probing depth (PD), gingival recession (GR), simplified oral hygiene index (OHIS), and percentage of sites with bleeding on probing (BOP) in the postmenopausal osteoporosis group were higher than those in the non-osteoporosis group[CAL(MD = 0.89(mm), 95 % CI [0.48,1.30], p < 0.00001), PD (MD = 0.27(mm), 95 % CI [0.13, 0.41], p = 0.0001), GR (MD = 0.28(mm), 95 % CI [0.20, 0.35], p < 0.00001), OHIS (MD = 1.32,95 % CI [1.12,1.51], p < 0.00001), BOP(MD = 12.71(%), 95 % CI [3.24,22.18], p = 0.009)]. Eleven studies found that bone mineral density (BMD) in the postmenopausal osteoporosis group was lower than that in non-osteoporosis group (MD = -0.41(U/cm2), 95 % CI [-0.77,-0.05], p = 0.03). The combined analysis results of the studies in the two groups showed that there were no significant differences in the loss of alveolar crestal height (ACH)[(MD = -1.76(%),95%CI [-3.64,0.12], p = 0.07)]. Conclusion: Postmenopausal osteoporosis patients are more likely to suffer from periodontitis, and the condition is easily aggravated.

3Cpro of FMDV inhibits type II interferon-stimulated JAK-STAT signaling pathway by blocking STAT1 nuclear translocation.

Foot-and-mouth disease virus (FMDV) has developed various strategies to antagonize the host innate immunity. FMDV Lpro and 3Cpro interfere with type I IFNs through different mechanisms. The structural protein VP3 of FMDV degrades Janus kinase 1 to suppress IFN-γ signaling transduction. Whether non-structural proteins of FMDV are involved in restraining type II IFN signaling pathways is unknown. In this study, it was shown that FMDV replication was resistant to IFN-γ treatment after the infection was established and FMDV inhibited type II IFN induced expression of IFN-γ-stimulated genes (ISGs). We also showed for the first time that FMDV non-structural protein 3C antagonized IFN-γ-stimulated JAK-STAT signaling pathway by blocking STAT1 nuclear translocation. 3Cpro expression significantly reduced the ISGs transcript levels and palindromic gamma-activated sequences (GAS) promoter activity, without affecting the protein level, tyrosine phosphorylation, and homodimerization of STAT1. Finally, we provided evidence that 3C protease activity played an essential role in degrading KPNA1 and thus inhibited ISGs mRNA and GAS promoter activities. Our results reveal a novel mechanism by which an FMDV non-structural protein antagonizes host type II IFN signaling.

Effects of Kinesio tape on pain and edema following surgical extraction of the third molar: A meta-analysis and systematic review.

BACKGROUND: Kinesio tape (KT) has been in extensive use for the rehabilitation of injuries related to sports, however, only a handful of studies have focused on the efficacy of KT following extraction of a third molar tooth. OBJECTIVE: The study aims to assess whether pain and edema following surgical extraction of the third molar can be reduced by KT. METHOD: This research was carried out following the principles of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Web of Science, Embase, PubMed, The Cochrane Library, CNKI, VIP, and WanFang Data databases were searched for trials published from their inception to eighth October 2021. They included published randomized controlled trials in Chinese or English languages. The methodological quality of the included studies was assessed using the Physiotherapy Evidence Database scale. Mean differences (MDs) with 95% confidence intervals (CIs) were used for the analysis of continuous data. The heterogeneity was measured using the I2 statistics. Then, Revman 5.4 software was employed for performing the meta-analysis. RESULTS: Eight studies comprising 453 participants in total were included. In comparison to the no kinesio tape group, KT did not furnish improved results on mouth opening ([MD = 0.36, 95% CI (-0.67, 1.40), p= 0.49]), and swelling ([MD =-1.24, 95% CI (-3.43, 0.95), p= 0.79]). However, KT manifested a reduction in operation time ([MD =-1.00, 95% CI (-1.93, -0.07), P= 0.04]), edema ([MD =-0.53, 95% CI (-0.88, -0.19), P= 0.003]), and pain intensity ([MD =-1.29, 95% CI (-1.86, -0.73), P< 0.00001]), favouring the kinesio tape group. Overall, the size of the effect was found in the small to moderate range. CONCLUSION: Despite the fact that KT can reduce pain and has been shown to have positive effects in several studies, there is no convincing evidence that it can reduce the swelling after surgical extraction of the third molar.

A pilot-scale study of the integrated floc-ultrafiltration membrane-based drinking water treatment process.

Although applications of the integrated ultrafiltration (UF) membrane have been investigated for years, most studies have been conducted at the lab scale. Here, a case study on the integrated Fe-based floc-UF process was presented. To enhance membrane performance, both pre-filtration (bag filter) and pre-oxidation were used as pretreatments to remove particles and inhibit the development of microorganisms. Results showed that the integrated process operated stably with pre-treatments, and the UF membrane fouling behavior could be divided into three different phases: slow increase rate (phase I), medium increase rate (phase II), and fast increase rate (phase III). In comparison to those in phases II and III, both natural organic matters and colloids were the main membrane fouling mechanisms during phase I, as the pollutants were not successfully removed by flocs initially. With the continuous injection of flocs, a loose cake layer became the main fouling mechanism during phase II, resulting in the deterioration of membrane fouling. During phase III, however, microorganisms (e.g., Proteobacteria) were inevitably nourished within the cake layer and played an important role in aggravating the degree of membrane fouling. During this integrated membrane-based process, several operating factors, including floc concentration, sludge discharge frequency, and the aeration rate during backwashing, played important roles in determining membrane performance. In addition, except for oxygen consumption, all the effluent quality parameters met the drinking water criteria followed in China (GB5749-2006).

Mannose-modified liposome designed for epitope peptide drug delivery in cancer immunotherapy.

BACKGROUND: Based on the interaction between cytotoxic T lymphocyte (CTL) dominant epitopes and dendritic cells (DCs), CD8+T cells are specifically activated into CTL cells. Targeted killing is a type of tumor vaccine for immunotherapy with great development potential. However, because of the disadvantages of poor stability in vivo and low uptake rate of DCs caused by single use of dominant epitope peptide drugs, its use is limited. Here, we investigated the antitumor potential of M-YL/LA-Lipo, a novel liposome drug delivery system. METHODS: We assembled mannose on the surface of liposome, which has a highly targeted effect on the mannose receptor on the surface of DCs. The dominant epitope peptide drugs were encapsulated into the liposome using membrane hydration method, and the encapsulation rate, release rate, in vitro stability, and microstructure were characterized using ultrafiltration method, dialysis method, and negative staining transmission electron microscopy. In addition, its targeting ability was verified by in vitro interaction with DCs, and its anticancer effect was verified by animal experiments. RESULTS: We have successfully prepared a liposome drug delivery system with stable physical and chemical properties. Moreover, we demonstrated that it was highly uptaken by DCs and promoted DC maturation in vitro. Furthermore, in vivo animal experiments indicated that M-YL/LA-Lipo specific CTL significantly inhibited the hematogenous spread of lung metastasis of triple negative breast cancer. CONCLUSIONS: we successfully constructed a new polypeptide liposome drug delivery system by avoiding the disadvantages of single use of dominant epitope peptide drugs and accurate targeted therapy for tumors.

Association between periodontal disease and osteoporosis in postmenopausal women: a protocol for systematic review and meta-analysis.

INTRODUCTION: Periodontal disease and osteoporosis are common chronic diseases, especially for the postmenopausal women. Several original studies explore the association, but there still controversial. Therefore, we will conduct this systematic review and meta-analysis to assess the association between periodontal disease and osteoporosis in postmenopausal women. METHODS AND ANALYSIS: This study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-analyses for Protocols. We will systematically search Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and Scopus from inception to August 2021 to collect all relevant publications, with no restrictions on publication date or languages. Study selection, data extraction and risk of bias assessment will be conducted independently by two trained reviewers independently. The Cochrane's tool for assessing risk of bias, Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality will be used for the risk of bias assessment. OR, HR and risk ratio with 95% CI were considered as the effect size for dichotomous outcomes, weighted mean difference with 95% CI were calculated as the effect size for continuous outcomes. Random-effects models will be used. Heterogeneity between studies will be assessed via the forest plot and I². Publication bias will detected by funnel plots, Begg's test and Egger's test. The subgroup analyses and sensitivity ananlyses will also be used to explore and interpret the heterogeneity. ETHICS AND DISSEMINATION: This study does not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021225746.

Biomimetic Melanosomes Promote Orientation-Selective Delivery and Melanocyte Pigmentation in the H2O2-Induced Vitiligo Mouse Model.

Extremely limited drug retention and depigmentation represent the greatest barriers against vitiligo treatment advancement. Here, inspired by biological melanosomes, the primary melanin transporter, we developed biomimetic melanosomes to combat reactive oxygen species (ROS)-mediated melanocyte damage and depigmentation. Briefly, methylprednisolone (MPS) and melanin-mimicking polydopamine (PDA) were encapsulated inside lysine-proline-valine (KPV)-modified deformable liposomes (KPV-Lipos). Owing to their phospholipid bilayer flexibility and the specific affinity for melanocortin 1 receptor (MC1R), KPV-Lipos exhibited 1.43-fold greater skin deposition than traditional liposomes. The binding of KPV and its receptor also contributed to activating the cAMP-tyrosinase (TYR) signaling pathway, improving the endogenous melanin content. In addition, PDA mimicked melanosomes as it effectively increased the exogenous melanin content and scavenged ROS. Meanwhile, MPS inhibited inflammatory cytokine secretion, limiting the depigmented area. Ultimately, the biomimetic melanosomes affected the skin color of mice with H2O2-induced vitiligo. These melanosomes show potential as a universal platform for the self-supply of melanin by self-driven melanin synthesis with exogenous supplementation. Furthermore, this study offers ideas for the production of artificial packed melanosome substitutes for melanocyte-related diseases.