Groundwater hydrochemical signatures, nitrate sources, and potential health risks in a typical karst catchment of North China using hydrochemistry and multiple stable isotopes.

Nitrate pollution in aquatic ecosystems has received growing concern, particularly in fragile karst basins. In this study, hydrochemical compositions, multiple stable isotopes (δ2H-H2O, δ18Ο-Η2Ο, δ15Ν-ΝΟ3-, and δ18Ο-ΝΟ3-), and Bayesian stable isotope mixing model (MixSIAR) were applied to elucidate nitrate pollution sources in groundwater of the Yangzhuang Basin. The Durov diagram identified the dominant groundwater chemical face as Ca-HCO3 type. The NO3- concentration ranged from 10.89 to 90.45 mg/L (average 47.34 mg/L), showing an increasing trend from the upstream forest and grassland to the downstream agricultural dominant area. It is worth noting that 47.2% of groundwater samples exceeded the NO3- threshold value of 50 mg/L for drinking water recommended by the World Health Organization. The relationship between NO3-/Cl- and Cl- ratios suggested that most groundwater samples were located in nitrate mixed endmember from agricultural input, soil organic nitrogen, and manure & sewage. The Self-Organizing Map (SOM) and Pearson correlations analysis further indicated that the application of calcium fertilizer, sodium fertilizer, and livestock and poultry excrement in farmland elevated NO3- level in groundwater. The output results of the MixSIAR model showed that the primary sources of NO3- in groundwater were soil organic nitrogen (55.3%), followed by chemical fertilizers (28.5%), sewage & manure (12.7%), and atmospheric deposition (3.4%). Microbial nitrification was a dominant nitrogen conversion pathway elevating NO3- levels in groundwater, while the denitrification can be neglectable across the study area. The human health risk assessment (HHRA) model identified that about 88.9%, 77.8%, 72.2%, and 50.0% of groundwater samples posing nitrate's non-carcinogenic health hazards (HQ > 1) through oral intake for infants, children, females, and males, respectively. The findings of this study can offer useful biogeochemical information on nitrogen pollution in karst groundwater to support sustainable groundwater management in similar human-affected karst regions.

Development of a tannic acid- and silicate ion-functionalized PVA-starch composite hydrogel for in situ skeletal muscle repairing.

The repair capacity of skeletal muscle is severely diminished in massive skeletal muscle injuries accompanied by inflammation, resulting in muscle function loss and scar tissue formation. In the current work, we developed a tannic acid (TA)- and silicate ion-functionalized tissue adhesive poly(vinyl alcohol) (PVA)-starch composite hydrogel, referred to as PSTS (PVA-starch-TA-SiO32-). It was formed based on the hydrogen bonding of TA to organic polymers, as well as silicate-TA ligand interaction. PSTS could be gelatinized in minutes at room temperature with crosslinked network formation, making it applicable for injection. Further investigations revealed that PSTS had skeletal muscle-comparable conductivity and modulus to act as a temporary platform for muscle repairing. Moreover, PSTS could release TA and silicate ions in situ to inhibit bacterial growth, induce vascularization, and reduce oxidation, paving the way to the possibility of creating a favorable microenvironment for skeletal muscle regeneration and tissue fibrosis control. The in vivo model confirmed that PSTS could enhance muscle fiber regeneration and myotube formation, as well as reduce infection and inflammation risk. These findings thereby implied the great potential of PSTS in the treatment of formidable skeletal muscle injuries.

Hydrogeochemical characterization, quality assessment, and potential nitrate health risk of shallow groundwater in Dongwen River Basin, North China.

Assessing groundwater geochemical formation processes and pollution circumstances is significant for sustainable watershed management. In the present study, 58 shallow groundwater samples were taken from the Dongwen River Basin (DRB) to comprehensively assess the hydrochemical sources, groundwater quality status, and potential risks of NO3- to human health. Based on the Box and Whisker plot, the cation's concentration followed the order of Ca2+ > Mg2+ > Na+ > K+, while anions' mean levels were HCO3- > SO42- > NO3- > Cl-. The NO3- level in groundwater samples fluctuated between 4.2 and 301.3 mg/L, with 67.2% of samples beyond the World Health Organization (WHO) criteria (50 mg/L) for drinking. The Piper diagram indicated the hydrochemical type of groundwater and surface water were characterized as Ca·Mg-HCO3 type. Combining ionic ratio analysis with principal component analysis (PCA) results, agricultural activities contributed a significant effect on groundwater NO3-, with soil nitrogen input and manure/sewage inputs also potential sources. However, geogenic processes (e.g., carbonates and evaporite dissolution/precipitation) controlled other ion compositions in the study area. The groundwater samples with higher NO3- values were mainly found in river valley regions with intense anthropogenic activities. The entropy weight water quality index (EWQI) model identified that the groundwater quality rank ranged from excellent (70.7%) and good (25.9%) to medium (3.4%). However, the hazard quotient (HQ) used in the human health risk assessment (HHRA) model showed that above 91.38% of groundwater samples have a NO3- non-carcinogenic health risk for infants, 84.48% for children, 82.76% for females, and 72.41% for males. The findings of this study could provide a scientific basis for the rational development and usage of groundwater resources as well as for the preservation of the inhabitants' health in DRB.

Fabrication of a Nanoscale Magnesium/Copper Metal-Organic Framework on Zn-Based Guided Bone Generation Membranes for Enhancing Osteogenesis, Angiogenesis, and Bacteriostasis Properties.

Recently, zinc (Zn) and its alloys have demonstrated great potential as guided bone regeneration (GBR) membranes to treat the problems of insufficient alveolar bone volume and long-term osseointegration instability during dental implantology. However, bone regeneration is a complex process consisting of osteogenesis, angiogenesis, and antibacterial function. For now, the in vivo osteogenic performance and antibacterial activity of pure Zn are inadequate, and thus fabricating a platform to endow Zn membranes with multifunctions may be essential to address these issues. In this study, various bimetallic magnesium/copper metal-organic framework (Mg/Cu-MOF) coatings were fabricated and immobilized on pure Zn. The results indicated that the degradation rate and water stability of Mg/Cu-MOF coatings could be regulated by controlling the feeding ratio of Cu2+. As the coating and Zn substrate degraded, an alkaline microenvironment enriched with Zn2+, Mg2+, and Cu2+ was generated. It significantly improved calcium phosphate deposition, differentiation of osteoblasts, and vascularization of endothelial cells in the extracts. Among them, Mg/Cu1 showed the best comprehensive performance. The superior antibacterial activity of Mg/Cu1 was demonstrated in vitro and in vivo, which indicated significantly enhanced bacteriostatic activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli as compared to that of the bare sample. Bimetallic Mg/Cu-MOF coating could properly coordinate the multifunction on a Zn membrane and could be a promising platform for promoting its bone regeneration, which could pave the way for Zn-based materials to be used as barrier membranes in oral clinical trials.

Applications of microalga-powered microrobots in targeted drug delivery.

Over the past decade, researchers have proposed a new class of drug delivery systems, bio-hybrid micro-robots, designed with a variety of living cell-driven micro-robots that utilize the unique mobility of natural organisms (bacteria, cells, exosomes, etc.) to transport effective drugs. Microalgae are considered potential drug delivery carriers. Recent studies have shown that microalga-based drug delivery systems exhibit excellent biocompatibility. In addition, microalgae have a large surfactant area, phototaxis, oxygen production, and other characteristics, so they are used as a carrier for the treatment of bacterial infections, cancer, etc. This review summarizes the modification of microalgae including click chemistry and electrostatic adsorption, and can improve the drug loading efficiency through dehydration and hydration strategies. The prepared microalgal drug delivery system can be targeted to different organs by different dosing methods or using external forces. Finally, it summarizes its antibacterial (gastritis, periodontitis, skin wound inflammation, etc.) and antitumor applications.

Identifying the hydrochemical features, driving factors, and associated human health risks of high-fluoride groundwater in a typical Yellow River floodplain, North China.

Fluoride enrichment (> 1.5 mg/L) in groundwater has become a global threat, particularly given the hazards to human health. This study collected 58 unconfined groundwater samples from Fengpei Plain in June 2022 for hydrochemical and stable isotope analyses combined with multiple methods to explore sources, influencing factors, and potential health hazards of groundwater F-. The results showed that groundwater F- concentration ranged from 0.08 to 8.14 mg/L, with an average of 1.91 mg/L; over 41.4% of them exceeded the acceptable level of 1.5 mg/L prescribed by the World Health Organization (WHO). The dominant hydrochemical facies changed from Ca·Mg-HCO3 and Ca·Mg-SO4·Cl type in low-F- groundwater to Na-HCO3 and Na-SO4·Cl water types in high-F- groundwater. The Self-Organizing Map (SOM) and ionic correlation analysis indicated that F- is positively correlated to pH, EC, Na+, K+, SO42-, and TDS, but negatively to Ca2+ and δ18O. Groundwater F- accumulation was primarily driven by F--bearing minerals dissolution such as fluorite. Simultaneously, the carbonates precipitation, positive cation exchange processes, and salt effect were conducive to groundwater F- enrichment. However, competitive adsorption between OH-/HCO3- and F-, evaporation, and anthropogenic activities only had a weak effect on the F- enrichment in groundwater. The hazard quotient (HQ) assessment results show that 67.2% of groundwater samples pose a non-carcinogenic risk (HQ > 1) for infants, followed by 53.4% for children, 32.8% for females, and 25.9% for males. The Monte Carlo simulation results agreed with those of the deterministic model that minors are more susceptible than adults. These findings are vital to providing insights into the geochemical behavior, driving factors, and drinking water safety of high-F- groundwater worldwide.

The Effect of Trans-Sutural Distraction Osteogenesis on Nasal Bone, Nasal Septum, and Nasal Airway in the Treatment for Midfacial Hypoplasia in Growing Patients.

The purposes of this study were to analyze the effect of trans-sutural distraction osteogenesis (TSDO) on nasal bone, nasal septum, and nasal airway in the treatment of midfacial hypoplasia. A total of 29 growing patients with midfacial hypoplasia who underwent TSDO by a single surgeon were enrolled. The 3-dimensional measurement of nasal bone and nasal septum changes was performed using computed tomography (CT) images obtained preoperatively (T0) and postoperatively (T1). One patient was selected to establish 3-dimensional finite element models to simulate the characteristics of nasal airflow field before and after traction. After traction, the nasal bone moved forward significantly ( P <0.01). The septal deviation angle was lower than that before traction (14.43±4.70 versus 16.86 ±4.59 degrees) ( P <0.01). The length of the anterior and posterior margin of the vomer increased by 21.4% ( P <0.01) and 27.6% ( P <0.01), respectively, after TSDO. The length of the posterior margin of the perpendicular plate of ethmoid increased ( P <0.05). The length of the posterior inferior and the posterior superior margin of the nasal septum cartilage increased ( P <0.01) after traction. The cross-sectional area of nasal airway on the deviated side of nasal septum increased by 23.0% after traction ( P <0.05). The analysis of nasal airflow field showed that the pressure and velocity of nasal airflow and the nasal resistance decreased. In conclusion, TSDO can promote the growth of the midface, especially nasal septum, and increase the nasal space. Furthermore, TSDO is conductive to improve nasal septum deviation and decrease nasal airway resistance.

Incorporation of Magnesium and Zinc Metallic Particles in PLGA Bi-layered Membranes with Sequential Ion Release for Guided Bone Regeneration.

Guided bone regeneration (GBR) membranes are commonly used for periodontal tissue regeneration. Due to the complications of existing GBR membranes, the design of bioactive membranes is still relevant. GBR membranes with an asymmetric structure can accommodate the functional requirements of different interfacial tissues. Here, poly(lactic acid-glycolic acid) (PLGA) was selected as the matrix for preparing a bi-layered membrane with both dense and porous structure. The dense layer for blocking soft tissues was incorporated with zinc (Zn) particles, while the porous layer for promoting bone regeneration was co-incorporated with magnesium (Mg) and Zn particles. Mg/Zn-embedded PLGA membranes exhibited 166% higher mechanical strength in comparison with pure PLGA membranes and showed suitable degradation properties with a sequential ion release behavior of Mg2+ first and continuously Zn2+. More importantly, the release of Zn2+ from bi-layered PLGA endowed GBR membranes with excellent antibacterial activity (antibacterial rate > 69.3%) as well as good cytocompatibility with MC3T3-E1 (mouse calvaria pre-osteoblastic cells) and HGF-1 (human gingival fibroblast cells). Thus, the asymmetric bi-layered PLGA membranes embedded with Mg and Zn particles provide a simple and effective strategy to not only reinforce the PLGA membrane but also endow membranes with osteogenic and antibacterial activity due to the continuous ion release profile, which serves as a promising candidate for use in GBR therapy.

Development of polydopamine functionalized porous starch for bleeding control with the assistance of NIR light.

Efficient hemorrhage control of severe wound injuries is an urgent medical need, deserving agents with promising blood coagulation and biocompatible characteristics. Current work developed polydopamine (PDA) functionalized porous starch powder (PS-PDA) for emergency bleeding treatment. The micro-morphology and elements, chemical groups, and porosity of PS-PDA were systematically characterized. Its comparison with porous starch (PS) revealed the promising potential of this composite in medical practice. On one hand, PS-PDA showed superior surface area and biomineralization affinity over PS, along with comparable hemo/cyto-compatibility. On the other hand, the photothermal effect of PDA under near Infrared (NIR) light paved the possibility to accelerate blood coagulation in situ. In vivo studies indicated PS-PDA can significantly reduce blood loss and improvement of hemostasis efficiency accompanied by NIR light exposure. These results suggest that this newly developed PS-PDA powder can serve as a promising hemostatic material for bleeding wound control.

Polydopamine functionalized porous starch (PS-PDA) was developed for bleeding controlPS-PDA showed superior surface area and biomineralization affinity over PSWith assistance of NIR irradiation, PS-PDA can accelerate blood coagulationPS-PDA showed therapeutic potential for both soft and hard tissue bleeding wound.

Effect of Different Temperatures on the Hydration Kinetics of Urea-Doped Cement Pastes.

Urea can solve the problem of concrete cracking due to temperature stress. However, its effect is affected by temperature. The influencing mechanism of temperature on urea-doped cement pastes is still unclear. This paper explores the effect of different temperatures on the hydration kinetics of urea-doped cement pastes. The isothermal calorimeter (TAM Air) was used to test hydration at three constant temperatures (20 °C, 40 °C, and 60 °C). The effects of the urea admixture and temperature on the hydration process and hydration kinetics parameters were investigated. The hydration mechanism was analyzed, and the changes in macroscopic mechanical compressive strength and porosity were tested. The results show that, as the urea content (UC) increases, the rate of hydration gradually decreases, and the increase in temperature promotes the inhibitory effect of urea. At 60 °C, UC of 8% can be reduced by 23.5% compared with the pure cement (PC) group's hydration rate. As the temperature increases from 20 °C to 60 °C, the Krstulovic-Dabic model changes from the NG-I-D process to the NG-D process. The effect of urea on the compressive strength of the cement is mainly shown in the early stage, and its effect on later strength is not obvious. In addition, urea will increase its early porosity. The porosity will gradually decrease in the later stage. The results of the study clarify the effect of temperature on urea-doped cement pastes. The optimal content of urea in cement is about 8%, which will provide theoretical guidance for solving the cracking problem of large-volume concrete due to temperature stress.

Octenyl Succinic Anhydride-Modified Starch Attenuates Body Weight Gain and Changes Intestinal Environment of High-Fat Diet-Fed Mice.

Effects of octenylsuccinate (OS) starch on body composition and intestinal environment in high-fat diet-fed mice were investigated. C57BL/6J mice were treated with a regular-fat (RF) diet, a high-fat (HF) diet, or a high-fat diet supplemented with OS starch (HFOSS). Fecal short-chain fatty acids (SCFAs) were quantified using gas chromatography, and the fecal microbiota profile was analyzed by 16S rDNA sequencing. One-way ANOVA and metastats analysis were performed for statistical analysis. After 22 weeks of feeding, mice in the HFOSS group had significantly lower body weight, body fat, liver weight, and cumulative food intake than those in the HF group but higher than that of the RF group. Fecal total SCFA, acetic, propionic, and butyric acid concentrations were significantly higher in the HFOSS group than that in the HF and RF groups. OS starch intervention increased the relative abundance of Parabacteroides, Alistipes, and Ruminiclostridium_5 and decreased that of Tyzzerella, Oscillibacter, Desulfovibrio, and Anaerotruncus compared with the RF and HF groups. The relative abundance of Lachnospiraceae_UCG-006 in the HFOSS group was lower than that in the HF group but higher than that in the RF group. In conclusion, OS starch prevents fat accumulation in high-fat diet-fed mice and might provide potential health benefits due to its fermentability in the gut and its ability to regulate gut microbial community structure.

A multi-functional SiO32--releasing hydrogel with bioinspired mechanical properties and biodegradability for vascularized skeletal muscle regeneration.

Vascularized skeletal muscle regeneration remains a great medical need but significant challenge. Biomaterial strategies that can facilitate the regeneration of muscle fibers and blood vessels are unavailable. Herein, we report a new cell- and drug-free biomaterial-based strategy for the repair of severely injured skeletal muscles. A novel multi-functional silicate ion-releasing hydrogel (SRH) was developed by dissolving PVA and starch in Na2SiO3 solutions, followed by freeze-thawing treatment. The mechanical properties and degradation profile of the SRH could be easily adjusted by altering the amylose/amylopectin ratio of starch. The SRH efficiently releases silicate ions to create a favorable microenvironment for enhanced skeletal muscle repair, while the mechanical properties and biodegradability of SRHs is adjusted to match the muscle regeneration environment. Silicate ions released from the SRH simultaneously promote myoblast proliferation and myogenic differentiation, decrease oxidative stress, and enhance the angiogenesis of vascular endothelial cells in vitro. Silicate ions released from the SRH scaffold with bioinspired mechanical properties and biodegradability promote the de novo formation of muscle fibers and blood vessels while inhibiting tissue fibrosis, leading to enhanced vascularized muscle regeneration in vivo. With multiple biofunctions and mechanical/degradation tunability, the SRH platform bears great potential in the skeletal muscle tissue engineering and treatment of formidable clinical problems such as volumetric muscle loss and sarcopenia.

Animal Models of Femur Head Necrosis for Tissue Engineering and Biomaterials Research.

Femur head necrosis, also known as osteonecrosis of the femoral head (ONFH), is a widespread disabling pathology mostly affecting young and middle-aged population and one of the major causes of total hip arthroplasty in the elderly. Currently, there are limited number of different clinical or medication options for the treatment or the reversal of progressive ONFH, but their clinical outcomes are neither satisfactory nor consistent. In pursuit of more reliable therapeutic strategies for ONFH, including recently emerged tissue engineering and biomaterials approaches, in vivo animal models are extremely important for therapeutic efficacy evaluation and mechanistic exploration. Based on the better understanding of pathogenesis of ONFH, animal modeling method has evolved into three major routes, including steroid-, alcohol-, and injury/trauma-induced osteonecrosis, respectively. There is no consensus yet on a standardized ONFH animal model for tissue engineering and biomaterial research; therefore, appropriate animal modeling method should be carefully selected depending on research purposes and scientific hypotheses. In this work, mainstream types of ONFH animal model and their modeling techniques are summarized, showing both merits and demerits for each. In addition, current studies and experimental techniques of evaluating therapeutic efficacy on the treatment of ONFH using animal models are also summarized, along with discussions on future directions related to tissue engineering and biomaterial research. Impact statement Exploration of tissue engineering and biomaterial-based therapeutic strategy for the treatment of femur head necrosis is important since there are limited options available with satisfactory clinical outcomes. To promote the translation of these technologies from benchwork to bedside, animal model should be carefully selected to provide reliable results and clinical outcome prediction. Therefore, osteonecrosis of the femoral head animal modeling methods as well as associated tissue engineering and biomaterial research are overviewed and discussed in this work, as an attempt to provide guidance for model selection and optimization in tissue engineering and biomaterial translational studies.

Effects of Optimized Acupuncture and Moxibustion Treatment on Depressive Symptoms and Executive Functions in Patients With Post-Stroke Depression: Study Protocol for a Randomized Controlled Trial.

Background: Post-stroke depression (PSD), a common neuropsychiatric comorbidity after stroke, has a negative impact on the functional recovery and quality of life of survivors. It lacks effective therapeutic drugs with good curative effects and few adverse reactions. Preliminary experiments have shown that the optimized acupuncture and moxibustion treatment (OAMT), including acupuncture, moxibustion, and auricular intradermal acupuncture, improved depressive symptoms and neurological deficits in patients with PSD. However, the evidence for its effectiveness is still insufficient. Hence, we designed this study to evaluate the efficacy and safety of the OAMT in the treatment of PSD and to explore its possible mechanism from the perspective of executive functions. Methods/Design: This is a randomized controlled trial, which comprises a total of 134 patients with PSD. Participants are randomized into intervention group and control group at a 1:1 ratio. All treatments are given five times per week for 4 weeks. The primary outcome is the severity of depression, which is evaluated by the Hamilton Depression Scale-17 (HAMD-17) and the Beck Depression Rating Scale (BDI). Secondary outcomes are executive abilities, which are measured by several neuropsychological tests, including the Stroop Color and Word Test (SCWT), the Trial Making Test (TMT), the Digit Symbol Substitution Test (DSST), and the Matrix Reasoning Test (MRT). All outcomes have been evaluated at baseline and weeks 4, 8, 12, and 20. At the same time, functional MRI (fMRI) is used to measure the functional connectivity in the cognitive control network (CCN) at baseline and 4 weeks after intervention. Discussion: This study aims to provide high-quality evidence for the efficacy and safety of the OAMT for treating PSD. In addition, this trial is the first trial to explore if the improvement condition of depression in the OAMT group is related to the improvement of executive functions and the favorable changes in the structure. Clinical Trial Registration: Chinese Clinical Trial Registry, identifier: ChiCTR2100048431.

Influence of Bone-Borne Trans-Sutural Distraction Osteogenesis Therapy on the Hard Palate of Growing Children With Cleft Lip and Palate.

ABSTRACT: The efficacy of trans-sutural distraction osteogenesis therapy (TSDO) in treating midfacial hypoplasia in children with cleft lip and palate has been confirmed. However, few studies have reported that changes occur in the palate after TSDO treatment. To study the effect of TSDO on palatal morphology and its relative position in the craniofacial region, we retrospectively collected and measured the computed tomography images of 29 growing children with cleft lip and palate and midfacial hypoplasia, before and after TSDO. The results showed that the length and height of the palate did not change significantly, but the width and arch length increased, and the anterior area was more pronounced than the posterior area, with the median palatine suture still centered without obvious deviation. This suggests lateral palate growth after distraction, most likely around the median palatine suture. The distance from the palate to the cranial base also increased after distraction, and the anterior nasal spine moved forward, whereas the palate rotated by an average of 10.04° downward from the center of the anterior nasal spine. The increasing distance between the palate and cranial base may result from the growth of the nasal bone or the skull base. The oropharyngeal airway volume was also increased by an average of 2256.36 mm3, which may be beneficial to children's ventilatory function. In conclusion, TSDO therapy has influence on patients' palatal morphology and position, which should be considered before surgery.

Prediction for HBsAg seroconversion in children with chronic hepatitis B.

BACKGROUND: To establish a prediction of HBsAg seroconversion in children with chronic hepatitis B (CHB), so as to help clinicians to choose therapeutic strategy. METHODS: A total of 63 children with HBeAg-positive CHB aged 1 to 17 years, who admitted to the fifth medical center of Chinese PLA general hospital and treated with interferon α (IFNα) 48 weeks were enrolled, the clinical data were measured. Based on the results of HBsAg seroconversion (HBsAg < 0.05 IU/mL and anti-HBsAg > 10 IU/L) at week 48, the patients were divided into HBsAg seroconversion (S) group and non-HBsAg seroconversion (NS) group. Multivariate COX regression was used to identify the impact factors associated with HBsAg seroconversion. A novel prediction index was established and the area under the receiver operating characteristic curve (AUROC) was used to assess the prediction for HBsAg seroconversion. RESULTS: The 63 patients were divided into S group (20.6%, 13/63) and NS group (79.4%, 50/63). Univariate and multivariate analysis identified age, baseline intrahepatic cccDNA and serum HBsAg levels were independent impact factors for HBsAg seroconversion. Intrahepatic cccDNA was positively correlated with serum HBsAg (r = 0.464, p = 0.000). AUROC of HBV cccDNA was 0.83 (95% CI 0.71 to 0.95) and AUROC of baseline HBsAg was 0.77 (95% CI 0.61 to 0.92). Intrahepatic cccDNA ≤ 0.08 log10 copies/106 cell is regarded as cutoff value, the positive predictive value(PPV) and negative predictive value(NPV) for HBsAg seroconversion were 86.8% and 60.0%, respectively, with a sensitivity of 92.0% and specificity of 56.2%. HBsAg ≤ 3.68 log10 IU/mL is used as cut off value, the PPV and NPV for HBsAg seroconversion were 91.2% and 56.3%, respectively; the sensitivity and specificity was 86.0% of 69.2%, respectively. There was no statistical difference between them for predicting HBsAg seroconversion (p = 0.146). CONCLUSIONS: HBsAg seroconversion can be predicted by the baseline serum HBsAg or intrahepatic cccDNA in children with CHB. Using the index, clinicians can choose more reasonable therapeutic strategy and reduce the waste of medical resources.

Strontium-calcium phosphate hybrid cement with enhanced osteogenic and angiogenic properties for vascularised bone regeneration.

Vascularized bone tissue engineering is regarded as one of the optimal treatment options for large bone defects. The lack of angiogenic properties and unsatisfactory physicochemical performance restricts calcium phosphate cement (CPC) from application in vascularized bone tissue engineering. Our previous studies have developed a starch and BaSO4 incorporated calcium phosphate hybrid cement (CPHC) with improved mechanical strength and handling properties. However, the bioactivity-especially the angiogenic ability-is still absent and requires further improvement. Herein, based on the reported CPHC and the osteogenic and angiogenic properties of strontium (Sr) ions, a strontium-enhanced calcium phosphate hybrid cement (Sr-CPHC) was developed to improve both biological and physicochemical properties of CPC. Compared to CPC, the initial setting time of Sr-CPHC was prolonged from 2.2 min to 20.7 min. The compressive strength of Sr-CPHC improved from 11.21 MPa to 45.52 MPa compared with CPC as well. Sr-CPHC was biocompatible and showed promotion of alkaline phosphatase (ALP) activity, calcium nodule formation and osteogenic relative gene expression, suggesting high osteogenic-inductivity. Sr-CPHC also facilitated the migration and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro and up-regulated the expression of the vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1). In vivo evaluation showed marked new bone formation in a rat calvarial defect model with Sr-CPHC implanted. Sr-CPHC also exhibited enhancement of neovascularization in subcutaneous connective tissue in a rat subcutaneous implantation model. Thus, the Sr-CPHC with the dual effects of osteogenesis and angiogenesis shows great potential for clinical applications such as the repair of ischemic osteonecrosis and critical-size bone defects.

Calcium phosphate-based composite cement: Impact of starch type and starch pregelatinization on its physicochemical properties and performance in the vertebral fracture surgical models in vitro.

Calcium phosphate cement (CPC) modified with native and pregelatinized normal corn and waxy maize starches was studied. Effects of starch pregelatinization and starch type on the physicochemical properties of CPC were investigated. CPC modified with pregelatinized normal corn starch (CPB-PNC) or pregelatinized waxy maize starch (CPB-PW) was evaluated by two vertebral fracture surgical models in vitro. Both granular and pregelatinized starches significantly improved the setting times and injectability of CPC, but only the pregelatinized starches improved the anti-collapsibility and compressive strength of CPC significantly. CPB-PW, whose micro-structure was compact and uniform, showed the best physicochemical properties. Addition of starch did not inhibit the hydro-reaction of CPC. Unmodified CPC had very poor dispersibility and could not apply in the tests of the surgical models. Pregelatinized starch especially waxy maize starch improved the dispersibility of CPC and showed good dispersion area, volume, improved pull-out force and maximum torque in the Sawbones sponge model. Similarly, in the minimally invasive kyphoplasty model, CPB-PNC and CPB-PW could disperse in the osteoporotic sheep vertebrae and improve the compressive strength of the sheep vertebral body. In conclusion, starch pregelatinization and starch botanical source affect the physicochemical properties of CPC significantly. Bone cements modified by different starches also performed differently in surgical models for osteoporotic vertebral fracture. Pregelatinized waxy maize starch may be a better candidate for CPC modification comparing to the pregelatinized normal corn starch.

Ultra-Conformable Ionic Skin with Multi-Modal Sensing, Broad-Spectrum Antimicrobial and Regenerative Capabilities for Smart and Expedited Wound Care.

While rapid wound healing is essential yet challenging, there is also an unmet need for functional restoration of sensation. Inspired by natural skin, an ultra-conformable, adhesive multi-functional ionic skin (MiS) with multi-modal sensing capability is devised for smart and expedited wound care. The base of MiS is a unique skin-like, conductive and self-adaptive adhesive polyacrylamide/starch double-network hydrogel (PSH) and self-powered, flexible, triboelectric sensor(s) is integrated on top of PSH for multi-tactile sensing. MiS could enhance wound contraction, collagen deposition, angiogenesis, and epidermis formation in a full-thickness skin defect wound model in vivo, while significantly inhibiting the biofilm formation of a wide range of microorganisms. MiS also exhibits multi-modal sensing capability for smart and instant therapeutics and diagnostics, including skin displacement or joint motion, temperature, pressure and tissue exudate changes of wound bed, and locally releasing drugs in a pH-responsive manner. More importantly, MiS could restore the skin-mimicking tactile sensing function of both touch location and intensity, and thus could be used as a human-machine interface for accurate external robotic control. MiS demonstrates a new comprehensive paradigm of combining wound diagnosis and healing, broad-spectrum anti-microbial capability and restoration of multi-tactile sensing for the reparation of severe wound.

Porous Core/Dense Shell PLA Microspheres Embedded with High Drug Loading of Bupivacaine Crystals for Injectable Prolonged Release.

Objective of the study was to design an injectable microsphere preparation with high drug loading of bupivacaine for prolonged release and local anesthetic. PLA or PLGA was used as the biodegradable matrix material to fabricate microspheres with the o/w emulsification-solvent evaporation method. The characterization of bupivacaine microspheres was observed by SEM, DSC, and XRPD. The microsphere preparation and extended drug release, as well as the plasma drug concentration and sciatic nerve blockade after injection of the microsphere formulation to rats were investigated. High drug-loading microspheres of more than 70% were successfully obtained with extended drug release over 5 days in vitro depending on the type of matrix and the feed ratio of drug to polymer. SEM, DSC, and XRPD results verified a novel microsphere structure characterized as the porous core composed of PLA material and form II bupivacaine crystals and dense shell formed of PLA layer. The mechanism that bupivacaine was dissolved inside the microsphere and diffused across the dense shell was suggested for drug release in vitro. The optimized PLA microsphere formulation showed low and steady plasma drug concentration over 5 days and prolonged duration of sensory and motor blockade of sciatic nerve lasted more than 3 days. Results indicated that the porous core-shell structure of PLA microsphere formulation would provide enormous potential as an injectable depot for locally prolonged delivery of bupivacaine and control of postoperative pain.