Urchin-like Hydroxyapatite/Graphene Hollow Microspheres as pH-Responsive Bone Drug Carriers.

Hydroxyapatite (HA) is the main inorganic component of human bones and teeth. It has good biocompatibility and bioactivity, which promotes its good application prospects in the field of bone drug carriers. In this study, tetraethylenepentamine-graphene (rGO-TEPA)/CaCO3:HA composite microspheres were prepared via microwave hydrothermal synthesis using rGO-TEPA/CaCO3 solid microspheres as intermediates. Furthermore, the incompletely transformed CaCO3 was removed by soaking in a citric acid buffer to obtain rGO-TEPA/HA hollow composite microspheres. The two types of as-prepared composite microspheres exhibited sea urchin-like structures, large BET surface areas, and good dispersibility. Mouse preosteoblast cells (MC3T3-E1) were used for in vitro cytotoxicity experiments. The in vitro cell viability test showed that the two composite drug carriers exhibited noncytotoxicity. Moreover, the doxorubicin (DOX) loading and releasing investigations revealed that the two types of prepared carriers had mild storage-release behaviors and good pH responsiveness. Hence, these rGO-TEPA/HA hollow microspheres have promising applications as bone drug carriers.

Pretreatment of rice straw with recycled ionic liquids by phase-separation process for low-cost biorefinery.

An efficient ionic liquids (ILs) recycle technology will increase the economic viability of lignocellulosic biorefinery. The availability of recycling 1-butyl-3-methylimidazolium chloride for rice straw (RS) pretreatment was conducted. The kosmotropic salt K3 PO4 (TKP) solution was used as antisolvent for cellulose precipitation and forming a three-phase system consisting of biomass, ILs-rich, and salt-rich phases. The upper ILs phase and the bottom TKP phase were recycled without additional purification, which significantly simplifies the process for recovering ILs. Subsequently, the RS pretreated with multiple reusing ILs (RPRS) were investigated by components analysis, structure evolution, enzymatic hydrolysis, and fermentation experiments. The results showed that unpurified reusing ILs led to further delignification and improvement of enzyme accessibility of the pretreated RS. The reducing sugar yield of RS pretreated with 8th reusing IL (8th RPRS) could still reach 98.9%, and the ethanol and succinic acid concentrations achieved 91.9 and 29.3 g/L by simultaneous saccharification and cofermentation. The present study demonstrated that the ILs recovered by phase-separation process could be used for RS pretreatment, and achieving high titer ethanol fermentation.

Efficient Uptake of 177 Lu-Porphyrin-PEG Nanocomplexes by Tumor Mitochondria for Multimodal-Imaging-Guided Combination Therapy.

The benefits to intracellular drug delivery from nanomedicine have been limited by biological barriers and to some extent by targeting capability. We investigated a size-controlled, dual tumor-mitochondria-targeted theranostic nanoplatform (Porphyrin-PEG Nanocomplexes, PPNs). The maximum tumor accumulation (15.6 %ID g-1 , 72 h p.i.) and ideal tumor-to-muscle ratio (16.6, 72 h p.i.) was achieved using an optimized PPN particle size of approximately 10 nm, as measured by using PET imaging tracing. The stable coordination of PPNs with 177 Lu enables the integration of fluorescence imaging (FL) and photodynamic therapy (PDT) with positron emission tomography (PET) imaging and internal radiotherapy (RT). Furthermore, the efficient tumor and mitochondrial uptake of 177 Lu-PPNs greatly enhanced the efficacies of RT and/or PDT. This work developed a facile approach for the fabrication of tumor-targeted multi-modal nanotheranostic agents, which enables precision and radionuclide-based combination tumor therapy.

Underwater drag-reducing effect of superhydrophobic submarine model.

To address the debates on whether superhydrophobic coatings can reduce fluid drag for underwater motions, we have achieved an underwater drag-reducing effect of large superhydrophobic submarine models with a feature size of 3.5 cm × 3.7 cm × 33.0 cm through sailing experiments of submarine models, modified with and without superhydrophobic surface under similar power supply and experimental conditions. The drag reduction rate reached as high as 15%. The fabrication of superhydrophobic coatings on a large area of submarine model surfaces was realized by immobilizing hydrophobic copper particles onto a precross-linked polydimethylsiloxane (PDMS) surface. The pre-cross-linking time was optimized at 20 min to obtain good superhydrophobicity for the underwater drag reduction effect by investigating the effect of pre-cross-linking on surface wettability and water adhesive property. We do believe that superhydrophobic coatings may provide a promising application in the field of drag-reducing of vehicle motions on or under the water surface.

Synergistic Effect of PEI and PDMAEMA on Transgene Expression in Vitro.

Polyethylenimine (PEI) and poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) have both been used for DNA delivery. PDMAEMA has been shown to exhibit better gene transfection efficiency but lower expression ability than PEI. We mixed the two polymers at different ratios to investigate whether the resulting "dual" polyplex (PEI/PDMAEMA/DNA) could enhance both gene transfection efficiency and DNA expression ability. Experimental results showed a significant increase in DNA internalization and DNA expression for the PDMAEMA/PEI/DNA polyplexes at a ratio of 1:3 or 1:9 (PDMAEMA: PEI), depending on cell type, in comparison with PEI/DNA, PDMAEMA/DNA, and PDMAEMA/PEI/DNA at other ratios. PDMAEMA/PEI/DNA polyplexes did not reduce cell viability. In contrast to with the conventional approach using covalently modified PEI, the proposed "combination" approach provided a more convenient and effective way to improve transgene expression efficiency.

Polydimethylsiloxane SlipChip for mammalian cell culture applications.

This paper reports a polydimethylsiloxane (PDMS) SlipChip for in vitro cell culture applications, multiple-treatment assays, cell co-cultures, and cytokine detection assays. The PDMS SlipChip is composed of two PDMS layers with microfluidic channels on each surface that are separated by a thin silicone fluid (Si-fluid) layer. The integration of Si-fluid enables the two PDMS layers to be slid to different positions; therefore, the channel patterns can be re-arranged for various applications. The SlipChip design significantly reduces the complexity of sample handling, transportation, and treatment processes. To apply the developed SlipChip for cell culture applications, human lung adenocarcinoma epithelial cells (A549) and lung fibroblasts (MRC-5) were cultured to examine the biocompatibility of the developed PDMS SlipChip. Moreover, embryonic pluripotent stem cells (ES-D3) were also cultured in the device to evaluate the retention of their stemness in the device. The experimental results show that cell morphology, viability and proliferation are not affected when the cells are cultured in the SlipChip, indicating that the device is highly compatible with mammalian cell culture. In addition, the stemness of the ES-D3 cells was highly retained after they were cultured in the device, suggesting the feasibility of using the SlipChip for stem cell research. Various cell experiments, such as simultaneous triple staining of cells and co-culture of MRC-5 with A549 cells, were also performed to demonstrate the functionalities of the PDMS SlipChip. Furthermore, we used a cytokine detection assay to evaluate the effect of endotoxin (lipopolysaccharides, LPS) treatment on the cytokine secretion of A549 cells using the SlipChip. The developed PDMS SlipChip provides a straightforward and effective platform for various on-chip in vitro cell cultures and consequent analysis, which is promising for a number of cell biology studies and biomedical applications.

Conjugated polymer/nanocrystal nanocomposites for renewable energy applications in photovoltaics and photocatalysis.

Conjugated polymer/nanocrystal composites have attracted much attention for use in renewable energy applications because of their versatile and synergistic optical and electronic properties. Upon absorbing photons, charge separation occurs in the nanocrystals, generating electrons and holes for photocurrent flow or reduction/oxidation (redox) reactions under proper conditions. Incorporating these nanocrystals into conjugated polymers can complement the visible light absorption range of the polymers for photovoltaics applications or allow the polymers to sensitize or immobilize the nanocrystals for photocatalysis. Here, the current developments of conjugated polymer/nanocrystal nanocomposites for bulk heterojunction-type photovoltaics incorporating Cd- and Pb-based nanocrystals or quantum dots are reviewed. The effects of manipulating the organic ligands and the concentration of the nanocrystal precursor, critical factors that affect the shape and aggregation of the nanocrystals, are also discussed. In the conclusion, the mechanisms through which conjugated polymers can sensitize semiconductor nanocrystals (TiO2 , ZnO) to ensure efficient charge separation, as well as how they can support immobilized nanocrystals for use in photocatalysis, are addressed.

Characteristics of corn starch/polyvinyl alcohol composite film with improved flexibility and UV shielding ability by novel approach combining chemical cross-linking and physical blending.

With the aim of effectively improving the performance of bio-friendly food packaging and circumventing the hazards associated with petroleum-based plastic food packaging, composite films of corn starch and polyvinyl alcohol were prepared using a new method that involved chemical cross-linking of glutaraldehyde and blending with cinnamon essential oil nanoemulsion (CNE). Glutaraldehyde and CNE enhance the film's network structure by chemical bonding and hydrogen bonding, respectively. This results in improved surface smoothness, mechanical properties, and UV shielding ability of the film. However, the films' surface hydrophilicity increased as a result of CNE, which is harmful for food preservation in high humidity. Overall, glutaraldehyde and CNE have a synergistic effect on some of the properties of the film which is mainly attributed to the films' structure improvement. The films have great potential for preparing flexible and UV-shielding films and offer new ideas for developing biodegradable films.

Targeting TGFß receptor-mediated snail and twist: WSG, a polysaccharide from Ganoderma lucidum, and it-based dissolvable microneedle patch suppress melanoma cells.

Cutaneous melanoma is a lethal skin cancer variant with pronounced aggressiveness and metastatic potential. However, few targeted medications inhibit the progression of melanoma. Ganoderma lucidum, which is a type of mushroom, is widely used as a non-toxic alternative adjunct therapy for cancer patients. This study determines the effect of WSG, which is a water-soluble glucan that is derived from G. lucidum, on melanoma cells. The results show that WSG inhibits cell viability and the mobility of melanoma cells. WSG induces changes in the expression of epithelial-to-mesenchymal transition (EMT)-related markers. WSG also downregulates EMT-related transcription factors, Snail and Twist. Signal transduction assays show that WSG reduces the protein levels in transforming growth factor ß receptors (TGFßRs) and consequently inhibits the phosphorylation of intracellular signaling molecules, such as FAK, ERK1/2 and Smad2. An In vivo study shows that WSG suppresses melanoma growth in B16F10-bearing mice. To enhance transdermal drug delivery and prevent oxidation, two highly biocompatible compounds, polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), are used to synthesize a dissolvable microneedle patch that is loaded with WSG (MN-WSG). A functional assay shows that MN-WSG has an effect that is comparable to that of WSG alone. These results show that WSG has significant potential as a therapeutic agent for melanoma treatment. MN-WSG may allow groundbreaking therapeutic approaches and offers a novel method for delivering this potent compound effectively.

Surface self-assembled PEGylation of fluoro-based PVDF membranes via hydrophobic-driven copolymer anchoring for ultra-stable biofouling resistance.

Stable biofouling resistance is significant for general filtration requirements, especially for the improvement of membrane lifetime. A systematic group of hyper-brush PEGylated diblock copolymers containing poly(ethylene glycol) methacrylate (PEGMA) and polystyrene (PS) was synthesized using an atom transfer radical polymerization (ATRP) method and varying PEGMA lengths. This study demonstrates the antibiofouling membrane surfaces by self-assembled anchoring PEGylated diblock copolymers of PS-b-PEGMA on the microporous poly(vinylidene fluoride) (PVDF) membrane. Two types of copolymers are used to modify the PVDF surface, one with different PS/PEGMA molar ratios in a range from 0.3 to 2.7 but the same PS molecular weights (MWs, ∼5.7 kDa), the other with different copolymer MWs (∼11.4, 19.9, and 34.1 kDa) but the similar PS/PEGMA ratio (∼1.7 ± 0.2). It was found that the adsorption capacities of diblock copolymers on PVDF membranes decreased as molar mass ratios of PS/PEGMA ratio reduced or molecular weights of PS-b-PEGMA increased because of steric hindrance. The increase in styrene content in copolymer enhanced the stability of polymer anchoring on the membrane, and the increase in PEGMA content enhanced the protein resistance of membranes. The optimum PS/PEGMA ratio was found to be in the range between 1.5 and 2.0 with copolymer MWs above 20.0 kDa for the ultrastable resistance of protein adsorption on the PEGylated PVDF membranes. The PVDF membrane coated with such a diblock copolymer owned excellent biofouling resistance to proteins of BSA and lysozyme as well as bacterium of Escherichia coli and Staphylococcus epidermidis and high stable microfiltration operated with domestic wastewater solution in a membrane bioreactor.

Neutralization of five subgenotypes of Enterovirus 71 by Taiwanese human plasma and Taiwanese plasma derived intravenous immunoglobulin.

Enterovirus 71 (EV71) commonly occurs in children, causing hand, foot and mouth disease (HFMD) in about 29% of patients. Studies have suggested that patients develop meningitis and encephalopathy with a mortality rate of 4-26%. EV71 subgenotypes including B4, B5, C2, C4 and C5 have caused HFMD epidemics in Taiwan. In terms of therapeutical strategy, intravenous immunoglobulin (IVIG) has been shown to improve patient conditions. In this study, the EV71 neutralizing titer was evaluated in 75 human plasmas and 8 lots of Taiwanese plasma derived IVIG. Results showed that human plasmas and IVIG significantly neutralized B4 and C2 subgenotypes. Four percent of human plasma contained neutralizing antibody titer of 1:128 against B4 and C2. Most IVIG lots possessed a median effective dose of over 100 against B4 and C2. IVIG lots had an average neutralizing capacity of 5.60, 0.90, 4.30, 1.12 and 0.77 log10 CCID50/ml against B4, B5, C2, C4 and C5, respectively. In conclusion, effective neutralization of B4 and C2 could be due to their earlier appearance in the EV71 epidemiology timeline of Taiwan. IVIG derived from Taiwanese plasma may be desirable for treatment of patients infected with EV71 of specific subgenotypes.

Manganese ferrite modified agricultural waste-derived biochars for copper ions adsorption.

Biochar is an eco-friendly, low-cost, and carbon-rich material. This study synthesized the biochars from three agricultural wastes, pinecone, white popinac, and sugarcane bagasse, and then modified them by manganese ferrite (MnFe2O4) co-precipitation. These biochars were applied as adsorbents for the removal of Cu(II) ions from water. All three different MnFe2O4-biochars have similar adsorption performances: rapid adsorption kinetics with equilibrium being reached within 5 hr of contact and significantly enhanced adsorption capacities of Cu(II) ions from water. The principal adsorption mechanisms were identified as complexation reactions, contributed by the carboxyl and hydroxyl groups by pristine biochars and by the Mn-O and Fe-O groups for all three MnFe2O4-biochars. The MnFe2O4-biochars can be reused for three cycles, with the maximum adsorption capacities of Cu(II) of the regenerated biochars declining with the loss of precipitated MnFe2O4.

Evaluation of Copper Levels in Dental Calculus of OSF Patients with Chewing Dried Areca-Nut Quids in Hunan Province of Mainland China.

Dental calculus is a potential material that can be used for assessing chronic exposure to trace heavy metals in oral cavity as it is a long-term reservoir. The aim of this study was to investigate the correlation between dental calculus copper levels and risk of oral submucous fibrosis (OSF) due to chewing dried areca-nut quids in Mainland China. This study included 34 OSF (grade 1) sufferers with dried areca-nut quids chewing as the patient group and 23 healthy individuals without areca-nut chewing as the control group. The dental calculus sample was obtained from all 57 participants and evaluated by inductively coupled plasma mass spectrometry (ICP-MS) for dental calculus level of copper. This work revealed that the mean copper level of dental calculus was significantly higher in OSF (grade 1) sufferers with areca-nut chewing than those in healthy individuals without areca-nut chewing (p < 0.001). This work provided an evidence to support that there may be a positive correlation between elevated levels of copper in dental calculus caused by chewing dried areca-nut quids and an increased risk of developing OSF in Mainland China.

Biomechanical analysis of alveolar bone stress around implants with different thread designs and pitches in the mandibular molar area.

Threaded implants have been shown to play an important role in increasing mechanical osseointegration. The aim of this study was to determine bone stress distribution when using different types of implant thread pitches and designs. Five 3D finite element models were constructed to simulate bone stresses induced in implant bodies with two types of thread form: triangular ("Tri" prefix) and trapezoidal ("Trap" prefix). The former had thread pitches of 0.8, 1.2, and 1.6 mm, while the latter had thread pitches of 1.2 and 1.6 mm. A biting load of 143 N was applied vertically and obliquely to the occlusal central fossa of the crown. The main effects of each level of the three factors investigated (loading type, pitch, and thread form) in terms of the stress value were computed for all models. Results indicated that the loading type was the main factor of influence on the peak compressive stress of the alveolar bone. Optimal thread pitch was 1.2 mm for a triangular-thread implant, and a trapezoidal-threaded implant with thread pitch of 1.6 mm had the lowest stress value among trapezoidal-threaded implants. This study concluded that each thread form has its unique optimal thread pitch with regard to lower concentration of bone stress. Clinically, this study suggests that in biomechanical consideration, thread pitch exceeding 0.8 mm is more appropriate for a screwed implant. For clinical cases that require greater bone-implant interface, trapezoidal-threaded implants with thread pitch of 1.6 mm provide greater primary stability and lower concentration of bone stress under different loading directions.

[Analysis of the causes of residual back pain in the early and late stages after percutaneous vertebral augmentation].

OBJECTIVE: To explore the influencing factors of the residual back pain in patient with osteoporotic vertebral compression fractures(OVCFs) in the early and late stages after percutaneous vertebral augmentation(PVA), and analyze the correlation between these factors and the residual back pain after PVA. METHODS: From March 2018 to December 2019, 312 patients with OVCFs who treated with PVA were collected. According to the inclusion and exclusion criteria, a total of 240 patients were included in this retrospective study. There were 59 males and 181 females, aged from 50 to 95 years old with an average of (76.11±10.72) years old, and 50 cases of fractures located in the thoracic region (T5-T10), 159 cases in the thoracolumbar region (T11-L2), and 31 cases in the lumbar region (L3 and below). The first day after PVA was regarded as the early postoperative period, and the seventh day was regarded as the late postoperative period. According to the visual analogue scale (VAS), the patients were divided into 4 groups:early postoperative pain relief group(group A, VAS≤4 scores), there were 121 patients, including 29 males and 92 females, aged from 50 to 90 years with an average of (75.71±11.00) years;early postoperative pain relief was not an obvious group (group B, VAS >4 scores), there were 119 patients, including 30 males and 89 females, aged from 53 to 95 years with an average of (76.51±10.46) years; late postoperative pain relief group (group C, VAS≤ 4 scores), there were 172 patients, including 42 males and 130 females, aged from 50 to 95 years with an average of (76.20±10.68) years; late postoperative pain relief was not obvious group (group D, VAS>4 scores), there were 68 patients, including 17 males and 51 females, aged from 53 to 94 years old with an average of (75.88±10.91) years old. The age, gender, bone mineral density(BMD), injured vertebral segment, preoperative thoracolumbar fascial condition, surgical methods, single or bilateral puncture, the amount of bone cement injection, anterior vertebral height recovery rate and central vertebral height recovery rate in the 4 groups were analyzed by univariate analysis. The statistically significant factors were put into a Logistic regression to analyze the correlation between these factors and residual back pain after PVA. RESULTS: Univariate analysis showed that the residual back pain in the early stage after PVA was correlated with BMD, preoperative thoracolumbar fascial injury, single or bilateral puncture, the amount of bone cement injection, anterior vertebral height recovery rate and central vertebral height recovery rate(P<0.05). The residual back pain in the late postoperative period was related to BMD, injured vertebral segment, surgical methods, the amount of bone cement injection, anterior vertebral height recovery rate and central vertebral height recovery rate(P<0.05). Multivariate Logistic regression analysis showed that thoracolumbar fascial injury(OR=4.938, P=0.001), single or bilateral puncture(OR=5.073, P=0.002) were positively correlated with the residual back pain in the early stage after PVA(B>0), which were risk factors;the BMD (OR=0.211, P=0.000) and anterior vertebral height recovery rate (OR=0.866, P=0.001) were negatively correlated with the residual back pain in the early stage after PVA(B<0), which were protective factors. In the late stage after PVA, the BMD(OR=0.448, P=0.003), the amount of bone cement injection (OR=0.648, P=0.004) and anterior vertebral height recovery rate (OR=0.820, P=0.000) were negatively correlated with residual back pain(B<0), which were protective factors. CONCLUSION: The decrease of BMD, injury of the thoracolumbar fascia, single or bilateral puncture, poor recovery of anterior vertebral height and insufficient injection of bone cement are closely related to the occurrence of residual back pain after PVA, which affect the relief of residual back pain in the early and late postoperative periods.

Logistic regression analysis on risk factors of augmented vertebra recompression after percutaneous vertebral augmentation.

OBJECTIVE: To explore the high-risk factors of augmented vertebra recompression after percutaneous vertebral augmentation (PVA) in the treatment of osteoporotic vertebral compression fracture (OVCF) and analyze the correlation between these factors and augmented vertebra recompression after PVA. METHODS: A retrospective analysis was conducted on 353 patients who received PVA for a single-segment osteoporotic vertebral compression fracture from January 2017 to December 2018 in our department according to the inclusion criteria. All cases meeting the inclusion and exclusion criteria were divided into two groups: 82 patients in the recompression group and 175 patients in the non-compression group. The following covariates were reviewed: age, gender, body mass index (BMI), injured vertebral segment, bone mineral density (BMD) during follow-up, intravertebral cleft (IVC) before operation, selection of surgical methods, unilateral or bilateral puncture, volume of bone cement injected, postoperative leakage of bone cement, distribution of bone cement, contact between the bone cement and the upper or lower endplates, and anterior height of injured vertebrae before operation, after surgery, and at the last follow-up. Univariate analysis was performed on these factors, and the statistically significant factors were substituted into the logistic regression model to analyze their correlation with the augmented vertebra recompression after PVA. RESULTS: A total of 257 patients from 353 patients were included in this study. The follow-up time was 12-24 months, with an average of 13.5 ± 0.9 months. All the operations were successfully completed, and the pain of patients was relieved obviously after PVA. Univariate analysis showed that in the early stage after PVA, the augmented vertebra recompression was correlated with BMD, surgical methods, volume of bone cement injected, preoperative IVC, contact between bone cement and the upper or lower endplates, and recovery of anterior column height. The difference was statistically significant (P < 0.05). Among them, multiple factors logistic regression elucidated that more injected cement (P < 0.001, OR = 0.558) and high BMD (P = 0.028, OR = 0.583) were negatively correlated with the augmented vertebra recompression after PVA, which meant protective factors (B < 0). Preoperative IVC (P < 0.001, OR = 3.252) and bone cement not in contact with upper or lower endplates (P = 0.006, OR = 2.504) were risk factors for the augmented vertebra recompression after PVA. The augmented vertebra recompression after PVP was significantly less than that of PKP (P = 0.007, OR = 0.337). CONCLUSIONS: The augmented vertebra recompression after PVA is due to the interaction of various factors, such as surgical methods, volume of bone cement injected, osteoporosis, preoperative IVC, and whether the bone cement is in contact with the upper or lower endplates.

Biochar boosts dark fermentative H2 production from sugarcane bagasse by selective enrichment/colonization of functional bacteria and enhancing extracellular electron transfer.

The influence of biochar (BC) on anerobic digestion (AD) of organic wastes have been widely studied. However, the effect of BC on rate-limiting step during AD of lignocellulosic waste, i.e. the hydrolysis and acidogenesis step, is rarely studied and the underlying mechanisms have not been investigated. In this study, the benefits of BC with respect to dark fermentative hydrogen production were explored in a fermentation system by a heat-shocked consortium from sewage sludge (SS) with pretreated sugarcane bagasse (PSCB) as carbon source. The results showed that biochar boosted biohydrogen production by 317.1% through stimulating bacterial growth, improving critical enzymatic activities, manipulating the ratio of NADH/NAD+ and enhancing electron transfer efficiency of fermentation system. Furthermore, cellulolytic Lachnospiraceae was efficiently enriched and electroactive bacteria were selectively colonized and the ecological niche was formed on the surface of biochar. Synergistic effect between functional bacteria and extracellular electron transfer (EET) in electroactive bacteria were assumed to be established and maintained by biochar amendment. This study shed light on the underlying mechanisms of improved performance of biohydrogen production from lignocellulosic waste during mesophilic dark fermentation by BC supplementation.

Case Report: Variations in the ALPL Gene in Chinese Patients With Hypophosphatasia.

Background: Hypophosphatasia (HPP) is an autosomal genetic disorder characterized biochemically by abnormal of bone parameters and serum alkaline phosphatase (ALP) activity as well as clinically by deficiency of teeth and bone mineralization. The clinical presentation is a continuum ranging from a prenatal lethal form with no skeletal mineralization to a mild form with late adult onset presenting with non-pathognomonic symptoms. ALP deficiency is the key to the pathogenesis of abnormal metabolism and skeletal system damage in HPP patients. Methods: We investigated five patients with skeletal dysplasia in the clinic. Whole-exome sequencing was performed in order to aid diagnosis of the patients. Results: Eight variants in the ALPL gene in the five unrelated Chinese patients (PA-1: c.649_650insC and c.707A > G; PA2: c.98C > T and c.707A > G; PA3: c.407G > A and c.650delTinsCTAA; PA4: c.1247G > T (homozygous); PA5: c.406C > T and c.1178A > G; NM_000478.5) were found. These variations caused two types of HPP: perinatal HPP and Odonto HPP. All cases reported in this study were autosomal recessive. Among the variants, c.1247G > T/p.Gly416Val (PA-4); c.1178A > G/p.Asn393Ser (PA-5) and c.707A > G/p.Tyr236Cys (PA-1, PA-2) have never been reported before. Conclusion: Clinical phenotypes of perinatal HPP (PA-1,PA-2,PA-3 and PA-4) include skeletal dysplasia, shorter long bones, bowing of long bones, tetraphocomelia, abnormal posturing and abnormal bone ossification. Odonto HPP (PA-5) only presents as dental abnormality with severe dental caries and decreased ALP activity. Our study extends the pool of ALPL variants in different populations.

Effect of 3D printed polycaprolactone scaffold with a bionic structure on the early stage of fat grafting.

Mature adipocytes are sensitive to stress and hypoxia, which are the two major obstacles in large-volume fat grafting. Bionic scaffolds are considered beneficial for fat grafting; however, their mechanism is still unclear. In this study, polycaprolactone scaffolds were fabricated by a 3D-printing technique and compounded with liposuction fat. They were implanted subcutaneously into nude mice. At different times, gross and histological observations were performed to evaluate the retention rates and histological morphologies. Adipocyte viability, apoptosis, and vascularization were analyzed by special immunostaining. Quantitative polymerase chain reaction was used to detect the variations in hypoxia and inflammation. The results showed that the volume and weight retentions in the scaffold group were higher than those in the fat group with the former exhibiting fewer vacuoles and less fibrosis. In immunostaining, elevated CD31+ capillaries, more perilipin+ adipocytes, and fewer TUNEL+ apoptotic cells were observed in the scaffold group by week 4. The lower expression of HIF-1α indicated the alleviation of hypoxia. In conclusion, the scaffold provided mechanical support to resist skin tension, thereby decreasing the interstitial pressure, and improving substance exchange and vascular ingrowth. In this regard, the scaffold attenuated hypoxia and promoted vascularization, making it a feasible method to increase long-term retention in fat grafting using scaffolds with suitable degradation rates and additional vascular maturation stimulation.

A self-doping conductive polymer hydrogel that can restore electrical impulse propagation at myocardial infarct to prevent cardiac arrhythmia and preserve ventricular function.

Following myocardial infarction (MI), necrotic cardiomyocytes (CMs) are replaced by fibroblasts and collagen tissue, causing abnormal electrical signal propagation, desynchronizing cardiac contraction, resulting in cardiac arrhythmia. In this work, a conductive polymer, poly-3-amino-4-methoxybenzoic acid (PAMB), is synthesized and grafted onto non-conductive gelatin. The as-synthesized PAMB-G copolymer is self-doped in physiological pH environments, making it an electrically active material in biological tissues. This copolymer is cross-linked by carbodiimide to form an injectable conductive hydrogel (PAMB-G hydrogel). The un-grafted gelatin hydrogel is prepared in a similar manner as a control. Both test hydrogels not only provide an optimal matrix for CM adhesion and growth but also maintain CM morphology and functional proteins. The conductivity of PAMB-G hydrogel is ca. 12 times higher than that of gelatin hydrogel. Microelectrode array analyses reveal that a heart placed on the PAMB-G hydrogel has a higher field potential amplitude than that placed on the gelatin hydrogel and can pass current from one heart to excite another heart at a distance. The injection of PAMB-G hydrogel into the scar zone following an MI in a rat heart improves electrical impulse propagation over that in a heart that has been treated with gelatin hydrogel, and synchronizes heart contraction, leading to preservation of the ventricular function and reduction of cardiac arrhythmia, demonstrating its potential for use in treating MI.