Engineering a targeted and safe bone anabolic gene therapy to treat osteoporosis in alveolar bone loss.

Alveolar bone loss in elderly populations is highly prevalent and increases the risk of tooth loss, gum disease susceptibility, and facial deformity. Unfortunately, there are very limited treatment options available. Here, we developed a bone-targeted gene therapy that reverses alveolar bone loss in patients with osteoporosis by targeting the adaptor protein Schnurri-3 (SHN3). SHN3 is a promising therapeutic target for alveolar bone regeneration, because SHN3 expression is elevated in the mandible tissues of humans and mice with osteoporosis while deletion of SHN3 in mice greatly increases alveolar bone and tooth dentin mass. We used a bone-targeted recombinant adeno-associated virus (rAAV) carrying an artificial microRNA (miRNA) that silences SHN3 expression to restore alveolar bone loss in mouse models of both postmenopausal and senile osteoporosis by enhancing WNT signaling and osteoblast function. In addition, rAAV-mediated silencing of SHN3 enhanced bone formation and collagen production of human skeletal organoids in xenograft mice. Finally, rAAV expression in the mandible was tightly controlled via liver- and heart-specific miRNA-mediated repression or via a vibration-inducible mechanism. Collectively, our results demonstrate that AAV-based bone anabolic gene therapy is a promising strategy to treat alveolar bone loss in osteoporosis.

Association between muscle quality index and periodontal disease among American adults aged ≥ 30 years: a cross-sectional study and mediation analysis.

OBJECTIVE: The muscle quality index (MQI) is a measurement of muscle quality that is directly related to overall health. There has been little study on the relationship between the muscle quality index and periodontitis in American people beyond 30 years. Therefore, this study aimed to explore the link between periodontitis and Muscle quality index (MQI) in older Americans. METHODS: Three thousand two hundred fifty-eight individuals (aged 30 to 59) who participated in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were considered eligible for the cross-sectional investigation. A hand dynamometer was used to determine the handgrip strength (HGS). Dual-energy X-ray absorptiometry was employed to calculate ASM (DXA). MQIArm was calculated by dividing the dominant hand's HGS by the dominant arm's ASM (in kg/kg). MQIApp was calculated by dividing the dominant hand's HGS by the ASM (in kg/kg). MQItotal was calculated by dividing the sum of the dominant and non-dominant hands by the ASM (in kg/kg). To investigate the link between muscle quality index and periodontal disease, the weighted multivariable logistic regression models were used. Using generalized additive models, it was determined if a nonlinear connection existed. Then, we developed a two-piece linear regression model and calculated the inflection point using a recursive approach. A mediation study was performed to determine how much of the impact of MQItotal on periodontitis was mediated by potential variables. RESULTS: Three thousand two hundred fifty-eight participants from the United States were enrolled. The OR (95% CI) for the relationship between MQItotal and periodontitis in the regression model with fully adjusted variables was 0.69 (0.53-0.91), for the connection between MQIArm and periodontitis was 0.90 (0.84-0.97), and for the association between MQIApp and periodontitis was 0.49 (0.30-0.80). MQItotal and periodontitis were shown to have a J-shaped relationship with a change point of 3.64. Before the change point, the OR (95% CI) was 0.69 (0.58, 0.82). In the analysis of drinking and married status, the interaction was statistically significant. Analysis of mediation showed that alcohol use was responsible for 0.4% (0.10 to 1.2) of the effect of MQItotal on periodontitis. CONCLUSION: In American adults aged over 30, the Muscle Quality Index (MQI) exhibited an independent negative correlation with moderate to severe periodontitis, demonstrating a J-shaped relationship. Furthermore, alcohol consumption may act as a mediator in the association between MQI and periodontitis.

A new fluorescence method for detection of famotidine based on polyethyleneimine-templated Ag nanoclusters.

A rapid, simple, inexpensive fluorescence analysis method for determination of famotidine based on polyethyleneimine (PEI)-capped Ag nanoclusters (PEI-Ag NCs) was developed. The study showed that addition of famotidine could cause efficient quenching of PEI-Ag NC fluorescence, as the presence of famotidine could cause aggregation of Ag NCs and quench its fluorescence. The sensitivity and selectivity of the method were investigated and experimental conditions such as buffer type, pH, temperature, and reaction time were optimized. Under optimized conditions, the results showed a linear profile from 3.7 × 10-8 to 3.7 × 10-5 mol/L, and had a detection limit of 1.6 × 10-9 mol/L (S/N = 3).

Amphiphilic Block Copolymers: A Novel Substance for Bitter-Masking in Aqueous Solutions.

It is a challenging task to suppress the bitterness of liquid preparations, especially for children. Bitter molecules are highly dispersible in liquids, leading to a strong and instant stimulation of the bitter receptors. At present, there is no effective way to correct this issue except for adding sweeteners, resulting in an unsatisfying taste. Based on the three-point contact theory, which is a universally accepted mechanism of bitterness formation, a new idea and application of amphiphilic block copolymers (ABCs) for bitterness suppression was proposed for the first time. We found that ABCs could widely inhibit the bitterness of four typical bitter substances. The mechanism is that ABCs self-assemble to form association colloids, which attract bitter components and reduce their distribution in the molecular form in solution. The bitter components were demonstrated to automatically embed in the spiral hydrophobic cavity of the hydrophobic chain of the ABCs, and their special interaction dispersed the positive electrostatic potential of bitter groups. The combination did not affect the pharmacokinetic parameters and pharmacodynamics of bitter drugs. These findings highlight the novel application of ABCs for the inhibition of bitterness and illuminate the underlying inhibition mechanisms.

Validation of the AGCU Expressmarker 16 + 22Y Kit: a new multiplex for forensic application.

Genotyping by targeting short tandem repeats (STRs) has been widely used in forensic applications. However, most commercial kits detect autosomal STRs or Y-STRs alone, which waste both time and opportunity. The AGCU Expressmarker 16 + 22Y Kit includes 16 autosomal and 22 Y-chromosomal STR loci and is designed for the forensic science field and obtaining quicker results. Here, we conducted the validation study according to Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines. Validation of PCR-based studies, species specificity, sensitivity, DNA mixture studies, inhibitors, precision, and sizing accuracy were performed. Furthermore, this system was also tested in 346 random male samples from Han, Hui, Tibetan, and Zhuang populations in China, showing its high power for forensic discrimination in the Chinese population. In addition, this system was able to deal with AMELY deletion cases, which can correctly identify sex in forensic criminal investigations. Our results suggested that the AGCU Expressmarker 16 + 22Y Kit is a useful tool for rapid criminal investigation.

Response-guided peginterferon therapy in patients with HBeAg-positive chronic hepatitis B: A randomized controlled study.

BACKGROUND & AIMS: Response-guided therapy has been confirmed to be an effective strategy for the treatment of chronic hepatitis C in the pegylated interferon (PegIFN) era, but no randomized trial utilizing this strategy has been conducted in chronic hepatitis B. METHODS: In this open-label, multicenter, randomized trial, HBeAg positive patients were treated with PegIFN (180µg/week) for 24weeks. Early responders (HBsAg <1500IU/ml and HBV DNA <10(5)copies/ml at week 24) received PegIFN for a further 24weeks (arm A), while non-early responders were randomized to PegIFN for another 24weeks (arm B), another 72weeks (arm C) or PegIFN for another 72weeks plus adefovir for 36weeks (arm D). The primary endpoint was the change of quantitative HBsAg from baseline to the end of follow-up (EOF). RESULTS: For non-early responders, 96-week PegIFN monotherapy did not lead to a greater reduction of HBsAg from baseline to EOF, compared with 48-week PegIFN (-0.71 vs. -0.67log10IU/ml, P=0.407). The rate of HBeAg seroconversion with HBV DNA <2000IU/ml at EOF were similar for arms B, C and D (17.9%, 23.9% and 25.0% respectively). For patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24, 38.4% and 37.0% achieved HBeAg seroconversion with HBV DNA <2000IU/ml at EOF respectively. CONCLUSIONS: Patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24 would benefit from continued PegIFN treatment. Extending the duration of PegIFN with or without adding adefovir did not show superiority over 48weeks PegIFN monotherapy. LAY SUMMARY: Extending the duration of pegylated interferon (PegIFN) alfa-2a is not recommended in HBeAg positive patients as treatment extension beyond 48weeks did not show convincing benefit. Patients who achieved HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml after 24-week PegIFNα-2a showed satisfactory outcome after the withdrawal of finite PegIFNα-2a treatment. CLINICAL TRIAL NUMBER: NCT01086085.

CD22ΔE12 as a molecular target for RNAi therapy.

B-precursor acute lymphoblastic leukaemia (BPL) is the most common form of cancer in children and adolescents. Our recent studies have demonstrated that CD22ΔE12 is a characteristic genetic defect of therapy-refractory clones in paediatric BPL and implicated the CD22ΔE12 genetic defect in the aggressive biology of relapsed or therapy-refractory paediatric BPL. The purpose of the present study is to evaluate the biological significance of the CD22ΔE12 molecular lesion in BPL and determine if it could serve as a molecular target for RNA interference (RNAi) therapy. Here we report a previously unrecognized causal link between CD22ΔE12 and aggressive biology of human BPL cells by demonstrating that siRNA-mediated knockdown of CD22ΔE12 in primary leukaemic B-cell precursors is associated with a marked inhibition of their clonogenicity. Additionally, we report a nanoscale liposomal formulation of CD22ΔE12-specific siRNA with potent in vitro and in vivo anti-leukaemic activity against primary human BPL cells as a first-in-class RNAi therapeutic candidate targeting CD22ΔE12.

An experimental study addressing the promotion of mandibular defect repair through the intermittent subcutaneous injection of parathyroid hormone.

PURPOSE: Parathyroid hormone (PTH) is a major regulator of bone metabolism. Various animal studies and clinical trials have addressed the treatment of osteoporosis and fracture healing with the intermittent administration of PTH, whereas few studies have investigated the effects of PTH on mandibular defect repair. This study sought to examine the feasibility of using recombinant human PTH (rhPTH) to promote the repair of mandibular defects and to provide a preliminary investigation of the underlying mechanisms of this phenomenon. MATERIALS AND METHODS: A mandibular defect model was established using Japanese white rabbits. The experimental animals were randomly divided into a control group that received postoperative subcutaneous injections of normal saline on alternate days and an experimental group that received postoperative subcutaneous injections of rhPTH 25 µg on alternate days. The experimental animals were sacrificed at 1, 2, 3, and 4 weeks after the operation to perform x-ray imaging and bone histomorphometric examinations of the defect areas. Changes in serum levels of bone-specific alkaline phosphatase (bALP) and osteoprotegerin (OPG) over time were examined. RESULTS: Compared with the control group, the experimental group exhibited newly generated bone matrix in the mandibular defect area at earlier stages. In the experimental group, the bone trabeculae were arranged in an orderly manner, and uniform calcification was observed. Marked hyperplasia of osteoblasts was observed in the new bone tissue of the experimental group, but significantly less hyperplasia of osteoblasts was observed in the control group. In the 2 groups, the average serum bALP and OPG levels increased after the operation and then gradually decreased. In the experimental group, levels of bALP and OPG at 1 week and 2 weeks after the operation were significantly different from preoperative levels. In the control group, the OPG level at 2 weeks after the operation was significantly different from the preoperative OPG level. A comparison of serum bALP and OPG levels at each examined time point showed no significant difference between the 2 groups. CONCLUSION: The intermittent subcutaneous injection of rhPTH 25 µg/day promotes the healing of mandibular defects in rabbits. The application of rhPTH may facilitate mandible regeneration by increasing quantities of osteoblasts, accelerating bone turnover metabolism, and upregulating OPG levels.

Preparation of pH-responsive polyurethane nano micelles and their antibacterial application.

Considering the differences in pH between bacterial infection microenvironment and normal tissues, a series of pH-responsive drug-release amphiphilic polyurethane copolymers (DPU-g-PEG) have been prepared in this work. Fourier transform infrared (FT-IR) spectroscopy and 1H NMR was selected to detect the structure of the condensed polymers. The DPU-g-PEG amphiphilic copolymers could form stable micelles with a hydrophilic shell of polyethylene glycol (PEG) and a hydrophobic core of polylactic acid (PLA). We loaded a model drug called triclosan onto DPU-g-PEG micelles and studied how pH affects their particle size, Zeta potential, and drug release performance. The results revealed that when exposed to acidic conditions, the surface potential of DPU-g-PEG micelles changed, the micelles' particle size increased, and the drug release performance was significantly enhanced. These results suggested that the micelles prepared in this study can release more antibacterial substances at sites of bacterial infection. Meanwhile, we also investigated the impact of different ratios of soft and hard segments on the properties of micelles, and the results showed that the pH responsiveness of micelles was strongest when the ratio of soft segments (PLLA diol + PEG 2000): 1,6-hexamethylene diisocyanate (HDI): 2,6-Bis-(2-hydroxy-ethyl)-pyrrolo[3,4-f]isoindole-1,3,5,7-tetraone (DMA) = 1: 1.2: 0.2. Furthermore, the results of inhibition zone test, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) all confirmed the antibacterial activity of triclosan-load DPU-g-PEG micelles. In conclusion, the DPU-g-PEG micelles produced in this study have the potential to be used as intelligent drug delivery systems in the biomedical field.

[Rickets-like genetic diseases].

This paper summarizes the clinical features, causative genes and treatment progress of patients with rickets-like genetic diseases, including X-linked hypophosphatemic rickets (XLH), hypophosphatasia, achondroplasia, vitamin D-dependent rickets, pycnodysostosis and ectodermal dysplasia, who visited the pediatric or child health clinic due to the symptoms of rickets, including bow legs, delayed closure of the anterior fontanelle, and sparse hair. Children with XLH usually go to hospital for bow legs and short stature, and biochemical evaluation reveals significantly low serum phosphorus so it is easily diagnosed. This disease is treated using phosphate mixture and 1,25(OH)2D3, which is different from the treatment of nutritional vitamin D deficiency rickets. Hypophosphatasia is characterized by a significant decrease in serum alkaline phosphatase, as well as normal serum calcium and phosphorus. The disease is caused by mutations in TNSALP gene. Patients with achondroplasia show short-limbed dwarfism and special face in addition to bow legs, but with normal serum calcium, phosphorus and alkaline phosphatase. Bone X-ray and FGFR3 gene test contribute to the diagnosis. Vitamin D-dependent rickets is an autosomal recessive disease, and active vitamin D supplement is effective in treatment of the disease. Patients with pycnodysostosis may be first seen at hospital because of large anterior fontanelle; in addition, they also show obtuse mandibular angle, dental abnormalities and dysplastic nails, which are caused by mutations in TSK gene. Children with ectodermal dysplasia may see a doctor for sparse hair, and they are easily misdiagnosed with nutritional vitamin D deficiency rickets. Ectodermal dysplasia is related to EDA, EDAR, EDARADD and WNT 10A genes.

Mendelian Randomisation Study on Association of Gut Microbiota and Periodontitis.

OBJECTIVE: Several studies have demonstrated the possible association between gut microbiota and periodontitis. The mechanism by which gut microbiota contribute to periodontitis remains unknown. METHODS: A 2-sample Mendelian randomisation (MR) study was conducted using publicly available Genome-Wide Association Studies (GWAS) data of European ancestry. The relationships between gut microbiota and tooth loss and periodontitis were assessed using summary-level data. Moreover, inverse variance weighted (IVW), MR-Egger, weighted median, and simple Mendelian were used. The results were further validated using sensitivity analyses. RESULTS: A total of 211 gut microbiota were studied, including 9 phyla, 16 classes, 20 orders, 35 families, and 131 genera. The IVW method identified 16 bacterial genera related to the risk of periodontitis and tooth loss. Lactobacillaceae was associated with an increased risk of periodontitis (odds ratio [OR], 1.40, 95% confidence interval [CI], 1.03-1.91, P<.001) and tooth loss (OR, 1.12; 95% CIs, 1.02-1.24, P = .002), whereas Lachnospiraceae UCG008 was linked to a lower risk of tooth loss (P = .041). There was no heterogeneity and horizontal pleiotropy in the sensitivity analysis. CONCLUSIONS: Several microorganisms were identified to be linked to the risk of periodontitis. Furthermore, the findings improved our understanding of gut microbiota and periodontitis pathology.

Integrating GWAS and proteome data to identify novel drug targets for MU.

Mouth ulcers have been associated with numerous loci in genome wide association studies (GWAS). Nonetheless, it remains unclear what mechanisms are involved in the pathogenesis of mouth ulcers at these loci, as well as what the most effective ulcer drugs are. Thus, we aimed to screen hub genes responsible for mouth ulcer pathogenesis. We conducted an imputed/in-silico proteome-wide association study to discover candidate genes that impact the development of mouth ulcers and affect the expression and concentration of associated proteins in the bloodstream. The integrative analysis revealed that 35 genes play a significant role in the development of mouth ulcers, both in terms of their protein and transcriptional levels. Following this analysis, the researchers identified 6 key genes, namely BTN3A3, IL12B, BPI, FAM213A, PLXNB2, and IL22RA2, which were related to the onset of mouth ulcers. By combining with multidimensional data, six genes were found to correlate with mouth ulcer pathogenesis, which can be useful for further biological and therapeutic research.

Interspersing CdS nanodots into iodine vacancy-rich BiOI sphere for photocatalytic lignin valorization.

Flower-like BiOI was decorated by CdS nanodots and followed by the introduction of iodine vacancies (VI) for photocatalytic sodium lignosulfonate (SLS) valorization under visible light. The iodine vacancies could adjust the band configuration, strengthen the light absorption and act as electron traps, while the intimate contact between BiOI and CdS nanodots provides a high-speed channel for charge transfer. As a consequence, the photocatalytic performance of SLS conversion into value-added vanillin was greatly improved over CdS/BiOI-VI compared with those of CdS, BiOI and CdS/BiOI. The highest yield of vanillin is 10.95 mg/gSLS over CdS/BiOI-VI, about 5, 8.7, 1.3 times those of CdS, BiOI, CdS/BiOI, respectively, and exceeding most related photocatalysts reported elsewhere. More significantly, as to the lignin from Masson pine and alkali lignin, the corresponding vanillin yield can reach 7.04 and 6.54 mg/glignin, respectively, under the same condition, which suggests the great potential and universality for photocatalytic lignin valorization over such CdS/BiOI-VI heterostructure.

Design and fabrication of intracellular therapeutic cargo delivery systems based on nanomaterials: current status and future perspectives.

Intracellular cargo delivery, the introduction of small molecules, proteins, and nucleic acids into a specific targeted site in a biological system, is an important strategy for deciphering cell function, directing cell fate, and reprogramming cell behavior. With the advancement of nanotechnology, many researchers use nanoparticles (NPs) to break through biological barriers to achieving efficient targeted delivery in biological systems, bringing a new way to realize efficient targeted drug delivery in biological systems. With a similar size to many biomolecules, NPs possess excellent physical and chemical properties and a certain targeting ability after functional modification on the surface of NPs. Currently, intracellular cargo delivery based on NPs has emerged as an important strategy for genome editing regimens and cell therapy. Although researchers can successfully deliver NPs into biological systems, many of them are delivered very inefficiently and are not specifically targeted. Hence, the development of efficient, target-capable, and safe nanoscale drug delivery systems to deliver therapeutic substances to cells or organs is a major challenge today. In this review, on the basis of describing the research overview and classification of NPs, we focused on the current research status of intracellular cargo delivery based on NPs in biological systems, and discuss the current problems and challenges in the delivery process of NPs in biological systems.

Phosphatidylserine-containing liposomes inhibit the differentiation of osteoclasts and trabecular bone loss.

Liposomes containing phosphatidylserine (PS) are engulfed by phagocytes including macrophages, microglia, and dendritic cells. PS liposomes (PSLs) mimic the effects of apoptotic cells on these phagocytes to induce the secretion of anti-inflammatory molecules and to inhibit the maturation of dendritic cells. However, the effects of PSLs on osteoclasts, which are also differentiated from the common myeloid precursors, remain to be determined. This study investigated the effects of PSLs on the osteoclastogenesis. In the rat bone marrow culture system, osteoclast precursors phagocytosed PSLs to secrete TGF-beta1 and PGE(2), which in turn inhibited osteoclastogenesis through the downregulation of receptor activator for NF-kappaB ligand, receptor activator of NF-kappaB, ICAM-1, and CD44. Consistent with these in vitro observations, i.m. injection of PSLs significantly increased the plasma level of TGF-beta1 and PGE(2) and decreased the expression of receptor activator for NF-kappaB ligand, receptor activator of NF-kappaB, and ICAM-1 in the skeletal tissues of ankle joints of rats with adjuvant arthritis (AA). A quantitative analysis using microcomputed tomography revealed that PSLs as well as TGF-beta1 together with PGE(2) significantly inhibited AA-induced trabecular bone loss. These observations strongly suggest that PSLs generate TGF-beta1 and PGE(2) release, leading to inhibit osteoclastogenesis and AA-induced trabecular bone loss. Because PS is a component of the cell membrane, PSLs therefore can be a potentially effective pharmacological intervention against abnormal bone loss, such as osteoporosis without deleterious side effects.

Preparation and characterization of 5-fluorouracil pH-sensitive niosome and its tumor-targeted evaluation: in vitro and in vivo.

The purpose of this study was to investigate preparation, characterization and tumor-targeted effect of pH-sensitive niosomes, composed of a nonionic surfactant mixed with cholesteryl hemisuccinate (CHEMS), a derivative of cholesterol (CHOL), as a pH-sensitive molecule. CHEMS was synthesized with CHOL and succinic acid, the structure of which was analyzed by Mass spectrometry (MS) and ¹H Nuclear magnetic resonance (¹H NMR) spectrum. Niosomes were prepared via film hydration-probe ultrasound method. Both normal niosomes and pH-sensitive niosomes showed spherical morphology under transmission electron microscope (TEM) with a average particle sizes of 172 ± 6.2 nm and 153 ± 4.7 nm, respectively. The thermotropic behavior, structure changes and interaction of 5-fluorouracil (5-Fu) with other materials were characterized by differential scanning calorimetry (DSC), and the disappearance of the melting peak of drug revealed the fact that drug was encapsulated in niosomes. Bulk-equilibrium reverse-dialysis method was chosen to investigate the behavior of drug release from normal niosomes and pH-sensitive niosomes in different pH medium, and the results showed that the noisome containing CHEMS had a pH-sensitive property. Tumor-targeted effect was proved by the fact that pH-sensitive niosomes showed a remarkable high concentration in tumor site of the mice transplanted with tumor cell.

[Etiology surveillance of hand-foot-mouth disease in Henan province between 2008 and 2011].

OBJECTIVE: To understand etiological types and distribution features of hand-foot-mouth disease (HFMD) in Henan province between 2008 and 2011. METHODS: A total of 30 486 specimens of feces, rectal swabs or throat swabs from HFMD patients were collected by each Municipal CDC in Henan from 2008 to 2011. The enterovirus 71 (EV71), coxsackie virus A16 (CA16) and other enterovirus (EV) were detected by RT-PCR or real time RT-PCR. The VP1 gene of EV71 was amplified and the sequences were analyzed by bioinformatics software. A genetic evolution tree of the sequence was constructed as well. RESULTS: The positive rates of EV71, CA16 and other EV were 62.70% (11 209/17 876), 12.03% (2150/17 876), 25.27% (4517/17 876) in 17 876 laboratory diagnosed cases, respectively. The differences were statistically significant (χ(2) = 157.17, P < 0.05). The positive rates of EV71, CA16 and other EV were 63.40% (7370/11 624), 11.58% (1346/11 624) and 25.02% (2908/11 624) in male patients and 61.40% (3839/6252), 12.86% (804/6252) and 25.74% (1609/6252) in female patients, respectively. The differences were statistically significant (χ(2) = 4.06, P < 0.05). The children under 5 years old were high-risk population of HFMD, accounting to 97.67% (17 459/17 876) of the laboratory-diagnosed patients.86.92% (15 537/17 876) cases were children between 1 to 3 years old. Constituent ratio of EV71 changed seasonally during a year, there was a high infection ratio of EV71 between April and June, especially in May, the infection ratio reached 69.34% (2384/3438). The positive rates of EV71, CA16 and other EV were 82.48% (5715/6929), 1.76% (122/6929) and 15.76% (1092/6929) among the 6929 laboratory-diagnosed severe cases, respectively. The positive rates of EV71 was higher than CA16 and other EV (χ(2) = 9259.17, 6170.81, P < 0.05, respectively). There were 117 deaths because of severe HFMD, 55 (47.01%) of which were laboratory confirmed. 50 death cases were infected by EV71, and according to the genetic evolution analysis, the VP1 gene of EV71 strain was belonged to subtype C4 of gene C. CONCLUSION: The EV71 and CA16 were the main pathogens which caused HFMD in Henan province, and EV71 virus was the dominant strain, belonging to C4 subtype of gene C.

Phosphatidylserine-containing liposomes suppress inflammatory bone loss by ameliorating the cytokine imbalance provoked by infiltrated macrophages.

Phosphatidylserine (PS)-containing liposomes (PSLs) strongly inhibit inflammatory bone loss in adjuvant arthritic (AA) rats. This effect was attributed to the inhibition of osteoclastogenesis through the secretion of prostaglandin E(2) and transforming growth factor-ß1 by osteoclast precursors after the phagocytosis of PSLs. However, infiltrated macrophages are considered to secrete anti-inflammatory mediators after phagocytosis of PSLs, which also contribute to inhibiting osteoclastogenesis. In the present study, we have attempted to elucidate the effects of PSLs on the phenotype of infiltrated macrophages during inflammatory bone loss. In AA rats, the ankle joints swelled with the infiltration of both macrophages and helper T cells into the synovium after a complete Freund's adjuvant injection. In the ankle joints of AA rats, approximately half of the infiltrated macrophages underwent a phenotypic change from interleukin (IL)-1ß-producing to IL-10-producing cells after the phagocytosis of PSLs. In lipopolysaccharide (LPS)-stimulated macrophages, PSLs also significantly decreased IL-1ß production, but increased IL-10 production. Moreover, PSLs inhibited the rapid activation of p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB, but enhanced the delayed activation of extracellular signal-regulated kinase (ERK) in LPS-stimulated macrophages. PSL-induced different influence on the activities of p38 MAPK and ERK is a likely underlying mechanism for phenotypic change of infiltrated macrophages after the phagocytosis of PSLs. This phenotypic change may be responsible for a significant decrease in the mean mRNA level of the receptor activator of NF-κB (RANK) and the RANK ligand (RANKL) in the ankle joint of PSL-treated AA rats, resulting in the inhibition of inflammatory bone loss.

In situ growth of amino-functionalized ZIF-8 on bacterial cellulose foams for enhanced CO2 adsorption.

Zeolitic imidazolate frameworks (ZIFs) hold great potential for carbon capture, while a major challenge for the practical application of ZIFs is the development of convenient three-dimensional bulk materials. Here, sustainable and biodegradable bacterial cellulose (BC) was used as the substrate for ZIF growth. Amino-functionalized ZIF-8 (ZIF-8-NH2) was prepared within BC substrate via an in situ growth approach. ZIF crystals were wrapped uniformly over cellulose fibers and the chelating effect between metal (zinc) ions and hydroxyl groups makes the composites have high interface affinity and compatibility. The resulting foams presented a high CO2 adsorption capacity of 1.63 mmol/g (25 °C, 1 bar). Moreover, ZIF-8-NH2@BC foams are facile to be regenerated by heating at 80 °C. This work provides a new avenue to construct ZIF/cellulose composites for gas treatment applications.

Biomechanical effects of reconstruction of the posterior structures after laminectomy with an individualized poly-ether-ether-ketone (PEEK) artificial lamina.

BACKGROUND: Laminectomy is a traditional method for treating lumbar diseases; however, the destruction of the posterior structures may cause postoperative symptoms. An individualized poly-ether-ether-ketone (PEEK) artificial lamina was designed to reconstruct the posterior structures after laminectomy. This study aimed to explore the biomechanical effects of reconstruction of the posterior structures with an individualized PEEK artificial lamina using validated finite element models. OBJECTIVE: To examine the biomechanical effects of individualized PEEK artificial lamina on postlaminectomy lumbar. METHODS: A finite element (FE) model of L3-5 was developed based on computed tomography images. Four surgical models (laminectomy, artificial lamina alone, ligament reconstruction, and osseointegration) were constructed, representing different stages of L4 artificial lamina implantation. The range of motion (ROM), intradiscal pressure (IDP), stresses in the annulus fibrosus at the surgical level and cephalad adjacent level, and stresses in the artificial lamina and screws were measured. RESULTS: The ROM, IDP, and stresses in the annulus fibrosus of the different artificial lamina models decreased compared to those of the laminectomy model at both surgical and adjacent levels for all motion patterns, most notably in the osseointegration model. In addition, the results of the stresses in the implants showed that the artificial lamina could enhance the lumbar isthmus and disperse the abnormally concentrated stresses after laminectomy. CONCLUSION: The application of a PEEK artificial lamina has the potential to stabilize the postlaminectomy lumbar spine and prevent adjacent segment disease (ASD) and iatrogenic lumbar deformities, resulting in a reduction in the incidence of post-lumbar surgery syndrome.