Biomineralized Piezoelectrically Active Scaffolds for Inducing Osteogenic Differentiation.

There is an endogenous electric field in living organisms, which plays a vital role in the development and regeneration of bone tissue. Therefore, self-powered piezoelectric material for bone repair has become hot research in recent years. However, the current piezoelectric materials for tissue regeneration still have the shortcomings of lack of biological activity and three-dimensional structure. Here, we proposed a three-dimensional polyurethane foam (PUF) scaffold coated with piezoelectric poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and modified by a calcium phosphate (CaP) mineralized coating. The preferred scaffold has an open circuit voltage and short circuit current output of 5 V and 200 nA. Combining the physical and chemical properties of the CaP coating, the piezoelectric signal of PVDF-HFP and the three-dimensional structure of PUF, the scaffold exhibits superior promotion of cell osteogenic differentiation and ectopic bone formation in vivo. The mechanism is attributed to an increase in intracellular Ca2+ levels in response to chemical and piezoelectric stimulation with the material. This research not only paves the way for the application of piezoelectric scaffolds to stimulate osteoblasts differentiation in situ, but also lays the foundation for the clinical treatment of long-term osteoporosis.

Temporal Trends of Legacy and Emerging PFASs from 2011 to 2021 in Agricultural Soils of Eastern China: Impacts of the Stockholm Convention.

The spatial variation and temporal trends of legacy and emerging per- and polyfluoroalkyl substances (PFASs) from 2011 to 2021 in agricultural soils of Eastern China, which is one of the largest PFAS production and consumption regions in the world, were evaluated. We found that PFOS concentration decreased by 28.2% during this period. Given that agricultural soils are sinks for persistent organic pollutants (POPs), our results suggest that the implementation of the Stockholm Convention and its indirect effects, combined with a voluntary phaseout, are effective for controlling PFOS pollution in agricultural soils in China. In addition, our results show that 19 out of 28 PFASs were detected in >40% of the samples, with concentrations being 17.6-1950 pg/g with a median of 373 pg/g. Further, legacy PFASs were major components, accounting for 63.8% of total PFASs. Based on the source appointment of PFASs via the Positive Matrix Factorization (PMF) model, the contribution ratio of consumer product industries has steadily increased from 6.10 to 26.2%, while both legacy and novel fluoropolymer industries have declined from 24.2 to 1.50 and 19.1 to 5.40%, further confirming the effectiveness of the Convention.

The efficacy of polidocanol sclerotherapy in mucocele of the minor salivary gland.

OBJECTIVES: Mucocele of the minor salivary gland is usually caused when the duct is injured, mucus leaks into the tissue space and the mucous gland are obstructed, which lead to cystic lesion formation and dilatation. Currently, there are multiple therapeutic methods available with various outcomes. This study aims to provide clinical evidence of polidocanol sclerotherapy for the treatment of mucocele of the minor salivary gland. METHODS: In this study, we injected polidocanol into 112 patients who were diagnosed with mucocele of the minor salivary gland and evaluated the treatment efficacy and safety systematically. RESULTS: Of the 122 cases, 102 cases were cured, eight cases showed remarkable remission, and two cases had partial remission. No recurrence was found during follow-up, and none of the cases showed an invalid effect, resulting in a total cure rate of 91.07%. No severe side effects were observed during treatment or the follow-up period. No significant difference in efficacy between different genders was found (P = 0.490). Polidocanol sclerotherapy for mucocele on the lower lip was more effective compared to mucocele on the inferior surface of the lingual apex (P = 0.035). CONCLUSION: Polidocanol sclerotherapy showed satisfying curative effects for mucocele of the minor salivary gland without causing side effects of anesthesia, trauma, or severe pain.

Contributions of Bioactive Molecules in Stem Cell-Based Periodontal Regeneration.

Periodontal disease is a widespread disease, which without proper treatment, may lead to tooth loss in adults. Because stem cells from the inflammatory microenvironment created by periodontal disease exhibit impaired regeneration potential even under favorable conditions, it is difficult to obtain satisfactory therapeutic outcomes using traditional treatments, which only focus on the control of inflammation. Therefore, a new stem cell-based therapy known as cell aggregates/cell sheets technology has emerged. This approach provides sufficient numbers of stem cells with high viability for treating the defective site and offers new hope in the field of periodontal regeneration. However, it is not sufficient for regenerating periodontal tissues by delivering cell aggregates/cell sheets to the impaired microenvironment in order to suppress the function of resident cells. In the present review, we summarize some promising bioactive molecules that act as cellular signals, which recreate a favorable microenvironment for tissue regeneration, recruit endogenous cells into the defective site and enhance the viability of exogenous cells.

Comparison of mandibular cortical thickness and QCT-derived bone mineral density (BMD) in survivors of childhood acute lymphoblastic leukemia: a retrospective study.

OBJECTIVE: To examine whether panoramic radiograph-determined mandibular cortical thickness correlated with quantitative computed tomography-derived bone mineral density (BMD) in survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: We identified patients treated for ALL at St. Jude Children's Research Hospital, seen in the After Completion of Therapy (ACT) Clinic between January of 2006 and January of 2014 who had QCT-derived BMD and panoramic radiographs obtained within 1 month of each other. Panoramic radiographs were independently scored by a pediatric radiologist, two pediatric dentists, and a general dentist using the Klemetti technique. We used the Spearman's rank correlation test and the multivariate regression model to investigate the effect of evaluator experience on results. RESULTS: The study cohort comprised 181 patients with 320 paired studies: 112 (62%) male, 112 (71%) were white. Median age at ALL diagnosis was 6.4 (range, 0-18.8) years. Median age at study was 11.9 (range, 3.3 to 29.4) years. The median average BMD was 154.6 (range, 0.73-256) mg/cc; median QCT Z-score (age and gender adjusted) was -0.875 (range, -5.04 to 3.2). We found very weak association between panoramic radiograph score and both QCT-BMD average (P = 0.53) and QCT Z-score (P = 0.39). Results were not influenced by level of reader experience. CONCLUSIONS: The Klemetti technique of estimating BMD does not predict BMD deficits in children and young adult survivors of ALL, regardless of reviewer expertise. Alternative methods are needed whereby dental healthcare providers can identify and refer patients at risk for BMD deficits for detailed assessment and intervention.

The Kumagai Method Utilizing the Pigeon Bottle Feeder with a Long Nipple: A Descriptive Study for the Development of Feeding Techniques for Children with Cleft Lip and/or Palate.

We aimed to identify the steps involved in the Kumagai method-an experimental nursing procedure to feed children with cleft lip and/or palate, using a feeder with a long nipple. We conducted a descriptive study, enrolling five specialist nurses who have mastered the Kumagai method. Their approaches were examined using structured interviews. Moreover, the participants were asked to perform the sequence of actions involved in this method while describing each step. Therefore, we were able to explore the Kumagai method in depth and step-by-step, including the following aspects: correct infant posture; correct feeding bottle holding position; nipple insertion into the child's mouth; and feeding process initiation, maintenance, and termination. Each step comprises several clinically relevant aspects aimed at encouraging the infant to suck with a closed mouth and stimulating chokubo-zui, i.e., simulation of the natural tongue movement during breastfeeding in children without a cleft palate. In conclusion, when performed correctly, the Kumagai method improves feeding efficiency in children with cleft lip and/or palate. Feeders with long nipples are rarely used in clinical practice; the Kumagai method might popularize their use, thereby improving the management of feeding practices for children with cleft lip and/or palate.

Shear Flow-Assembled Janus Membrane with Bifunctional Osteogenic and Antibacterial Effects for Guided Bone Regeneration.

Guided bone regeneration (GBR) membranes that reside at the interface between the bone and soft tissues for bone repair attract increasing attention, but currently developed GBR membranes suffer from relatively poor osteogenic and antibacterial effects as well as limited mechanical property and biodegradability. We present here the design and fabrication of a bifunctional Janus GBR membrane based on a shear flow-driven layer by a layer self-assembly approach. The Janus GBR membrane comprises a calcium phosphate-collagen/polyethylene glycol (CaP@COL/PEG) layer and a chitosan/poly(acrylic acid) (CHI/PAA) layer on different sides of a collagen membrane to form a sandwich structure. The membrane exhibits good mechanical stability and tailored biodegradability. It is found that the CaP@COL/PEG layer and CHI/PAA layer contribute to the osteogenic differentiation and antibacterial function, respectively. In comparison with the control group, the Janus GBR membrane displays a 2.52-time and 1.84-time enhancement in respective volume and density of newly generated bone. The greatly improved bone repair ability of the Janus GBR membrane is further confirmed through histological analysis, and it has great potential for practical applications in bone tissue engineering.

Graphene/ chitosan tubes inoculated with dental pulp stem cells promotes repair of facial nerve injury.

Introduction: Facial nerve injury significantly impacts both the physical and psychological] wellbeing of patients. Despite advancements, there are still limitations associated with autografts transplantation. Consequently, there is an urgent need for effective artificial grafts to address these limitations and repair injuries. Recent years have witnessed the recognition of the beneficial effects of chitosan (CS) and graphene in the realm of nerve repair. Dental pulp stem cells (DPSCs) hold great promise due to their high proliferative and multi-directional differentiation capabilities. Methods: In this study, Graphene/CS (G/CST) composite tubes were synthesized and their physical, chemical and biological properties were evaluated, then DPSCs were employed as seed cells and G/CST as a scaffold to investigate their combined effect on promoting facial nerve injury repair. Results and Disscussion: The experimental results indicate that G/CST possesses favorable physical and chemical properties, along with good cyto-compatibility. making it suitable for repairing facial nerve transection injuries. Furthermore, the synergistic application of G/CST and DPSCs significantly enhanced the repair process for a 10 mm facial nerve defect in rabbits, highlighting the efficacy of graphene as a reinforcement material and DPSCs as a functional material in facial nerve injury repair. This approach offers an effective treatment strategy and introduces a novel concept for clinically managing facial nerve injuries.

A novel bi-layered asymmetric membrane incorporating demineralized dentin matrix accelerates tissue healing and bone regeneration in a rat skull defect model.

Objectives: The technique of guided bone regeneration (GBR) has been widely used in the field of reconstructive dentistry to address hard tissue deficiency. The objective of this research was to manufacture a novel bi-layered asymmetric membrane that incorporates demineralized dentin matrix (DDM), a bioactive bone replacement derived from dentin, in order to achieve both soft tissue isolation and hard tissue regeneration simultaneously. Methods: DDM particles were harvested from healthy, caries-free permanent teeth. The electrospinning technique was utilized to synthesize bi-layered DDM-loaded PLGA/PLA (DPP) membranes. We analyzed the DPP bilayer membranes' surface topography, physicochemical properties and degradation ability. Rat skull critical size defects (CSDs) were constructed to investigate in vivo bone regeneration. Results: The synthesized DPP bilayer membranes possessed suitable surface characteristics, acceptable mechanical properties, good hydrophilicity, favorable apatite forming ability and suitable degradability. Micro-computed tomography (CT) showed significantly more new bone formation in the rat skull defects implanted with the DPP bilayer membranes. Histological evaluation further revealed that the bone was more mature with denser bone trabeculae. In addition, the DPP bilayer membrane significantly promoted the expression of the OCN matrix protein in vivo. Conclusions: The DPP bilayer membranes exhibited remarkable biological safety and osteogenic activity in vivo and showed potential as a prospective candidate for GBR applications in the future.

[Effects and Mechanisms of Polystyrene Microplastics on Extracellular Antibiotic Resistance Genes in Wastewater].

Microplastics (MPs) and antibiotic resistance genes (ARGs) are typical co-existing emerging pollutants in wastewater treatment plants. MPs have been shown to alter the distribution pattern of ARGs in sludge, but their effects on free extracellular ARGs (feARGs) in wastewater remain unclear. In this study, we used fluorescence quantitative PCR to investigate the dynamics of feARGs (including tetC, tetO, sul1, and sul2) in wastewater and their transition mechanisms after 60 d of exposure to typical MPs (polystyrene, PS). The results showed that the absolute abundance of tetracycline feARGs decreased by 28.4 %-76.0 % and 35.2 %-96.2 %, respectively, under nm-level and mm-level PS exposure and changed by -55.4 %-122.4 % under µm-level PS exposure. The abundance of sul1 showed a trend of nm-level > µm-level > mm-level upon PS exposure, and the changes in sul1 abundance was greater with ρ(PS)=50 mg·L-1 exposure. The relative abundance of sul2 was reduced by 25.4 %-42.6 % and 46.1 %-90.3 % after µm-level and mm-level PS exposure, respectively, and increased by 1.9-3.9 times after nm-level PS exposure, and the sul2 showed a higher reduction at ρ (PS)=50 mg·L-1 exposure than that at ρ (PS)=0.5 mg·L-1. The Pearson correlation analysis showed that the relative abundance of feARGs during PS exposure was positively correlated with cell membrane permeability and typical mobile genetic elements (intI1) abundance and negatively correlated with reactive oxygen species level. Our findings elucidated the effects and corresponding mechanisms of PS on the growth and mobility of feARGs in wastewater, providing a scientific basis for the control of the combined MPs and ARGs pollution in wastewater.

Characterization, hazard identification, and risk assessment of volatile organic compounds in Poly(butylene adipate-co-terephthalate)-based food contact articles.

The chemical safety of poly (butylene adipate-co-terephthalate) (PBAT) based food contact articles (FCAs) has aroused increasing toxicological concerns in recent years, but the chemical characterization and associated risk assessment still remain inadequate as it fails to elucidate the distribution pattern and discern the potential genotoxic and carcinogenic hazards of the identified substances. Herein, the volatile organic compounds (VOCs) in 50 batches of PBAT-based FCAs of representative categories and 10 batches of PLA and PBAT pellets were characterized, by which 237 VOCs of 10 chemical categories were identified and exhibited characteristic distribution patterns in the chemical spaces derived from their molecular descriptors. Chemical hazards associated with the identified VOCs were discerned by a hazard-driven classification scheme integrating hazard-related knowledge from multiple publicly available sources, and 34 VOCs were found to bear genotoxic or carcinogenic hazards and to feature higher average molecular weight than the other VOCs. Finally, the Risk and hazard quotient (HQ) calculated as the metrics of risk suggested that all identified VOCs posed acceptable risks (Risk<10-4 or HQ < 1), whereas oxolane, butyrolactone, N,N-dimethylacetamide, 2-butoxyethanol, benzyl alcohol, and 1,2,3-trichloropropane posed non-negligible (Risk>10-6) genotoxic or carcinogenic risk and thus should be of prioritized concern to promote the chemical safety of PBAT-based FCAs.

Effective Scald Wound Functional Recovery Patch Achieved by Molecularly Intertwined Electrical and Chemical Message in Self-Adhesive Assemblies.

Bioactive materials that communicate with bio-tissues via simultaneous chemical and electrical information promise an advanced medical treatment strategy. Rational design of simultaneous chemically and electrically active materials is still challenging. In this study, we develop a bioactive wound healing patch that enables functional recovery of scald skin wounds by integrating electrically and chemically active units at the molecular level. The patch should be used with massages for 10 min daily during the recovery process. This healing patch consists of a closely intertwined piezoelectric poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF) film and a self-adhesive poly(N,N-dimethylacrylamide) (PDMAA) hydrogel layer, which permits itself to adhere on skin wounds reversibly. Frequency-dependent electrical and chemical dose delivery is achieved in response to mechanical stimuli via the electrical-chemical crosstalk within the healing patch. Animal scald experiments show that the patch can effectively guide the functional recovery of grade I and shallow grade II scald wounds, promoting proper collagen deposition and hair follicle, blood vessel, and gland regeneration. Integrating electrically and chemically active units at the molecular level in treatment devices provides a new design concept for tissue engineering and medical treatment materials.

Successful treatment of new-onset diabetes mellitus and IgA nephropathy after COVID-19 vaccination: a case report.

De novo glomerular injuries or relapse of nephropathy following COVID-19 vaccine has been reported. Here we present the first case of successful treatment of new-onset diabetes mellitus and biopsy-proven IgA nephropathy after COVID-19 vaccination. A 56-year-old man with no known medical history of renal dysfunction or diabetes mellitus developed both within 3 months after receiving a third dose of inactivated COVID-19 vaccine (Vero cells). His symptoms were characterized by brown urine, severe dry mouth, and excessive thirst. Randomly acquired blood glucose levels exceeded 33.3 mmol/L. A kidney biopsy showed IgA nephropathy. He was started on insulin for glycemic control. After glucocorticoid and cyclophosphamide treatment, oral tablets of repaglinide, combined with acarbose, controlled blood glucose and stabilized kidney function. This case is unique because the kidneys and pancreas were simultaneously affected by the vaccine. Successful treatment of the disease proved that cyclophosphamide combined with glucocorticoids were effective and that blood glucose was successfully controlled. This treatment option could be useful in similar cases in the future.

Self-Assembled Core-Shell Nanoscale Coordination Polymer Nanoparticles Carrying a Sialyltransferase Inhibitor for Cancer Metastasis Inhibition.

Despite hypersialylation of cancer cells together with a significant upregulation of sialyltransferase (ST) activity contributes to the metastatic cascade at multiple levels, there are few dedicated tools to interfere with their expression. Although transition state-based ST inhibitors are well-established, they are not membrane permeable. To tackle this problem, herein, we design and construct long-circulating, self-assembled core-shell nanoscale coordination polymer (NCP) nanoparticles carrying a transition state-based ST inhibitor, which make the inhibitor transmembrane and potently strip diverse sialoglycans from various cancer cells. In the experimental lung metastasis and metastasis prevention models, the nanoparticle device (NCP/STI) significantly inhibits metastases formation without systemic toxicity. This strategy enables ST inhibitors to be applied to cells and animals by providing them with a well-designed nanodelivery system. Our work opens a new avenue to the development of transition state-based ST inhibitors and demonstrates that NCP/STI holds great promise in achieving metastases inhibition for multiple cancers.

Facile method for the fabrication of robust polyelectrolyte multilayers by post-photo-cross-linking of azido groups.

In this letter, we have developed a facile method to enhance the stability of polyelectrolyte multilayers. We fabricate conventional polyelectrolyte multilayers of PAH/PAA through electrostatic layer-by-layer (LbL) assembly and then postinfiltrate photosensitive cross-linking agent 4,4'-diazostilbene-2,2'-disulfonic acid disodium salt into the LbL films. After cross-linking by UV irradiation, the stability of the photo-cross-linked multilayer is highly improved as evidenced by the lack of dissolution under ultrasonication in saturated SDS aqueous solutions for 10 min. Moreover, by taking advantage of the different stability of the LbL film before and after UV irradiation, a patterned surface can be achieved.

A healing promoting wound dressing with tailor-made antibacterial potency employing piezocatalytic processes in multi-functional nanocomposites.

Developing a novel antibiotics-free antibacterial strategy is essential for minimizing bacterial resistance. Materials that not only kill bacteria but also promote tissue healing are especially challenging to achieve. Inspired by chemical conversion processes in living organisms, we develop a piezoelectrically active antibacterial device that converts ambient O2 and H2O to ROS by piezocatalytic processes. The device is achieved by mounting nanoscopic polypyrrole/carbon nanotube catalyst multilayers onto piezoelectric-dielectric films. Under stimuli by a hand-held massage device, the sterilizing rates for S. aureus and E. coli reach 84.11% and 94.85% after 10 minutes of operation, respectively. The antibacterial substrate at the same time preserves and releases drugs and presents negligible cytotoxicity. Animal experiments demonstrate that daily treatment for 10 minutes using the device effectively accelerates the healing of infected wounds on the backs of mice, promoting hair follicle generation and collagen deposition. We believe that this report provides a novel design approach for antibacterial strategies in medical treatment.

Dual stimuli-responsive nanocarriers based on polyethylene glycol-mediated schiff base interactions for overcoming tumour chemoresistance.

Multifunctional and stimulus-sensitive intelligent nanodrug delivery systems (NDDSs) can significantly optimize the effectiveness of theranostic agents for cancer treatment. In this study, redox and pH dual-responsive nanocarriers (CPNPs) were prepared through molecular assembly by utilizing the Schiff base interactions of cystamine (Cys), PEG-NH2 and formaldehyde (FA) under aqueous conditions with a one-pot, one-step technique. First, the degradation products of CPNPs exhibited good biocompatibility, and the high concentration of intact CPNPs (200 µg/mL) could inhibit the growth of cells. In addition, doxorubicin (DOX) was encapsulated in CPNPs simply by changing the pH (DOX@CPNPs), and pH/GSH-responsive release behaviour was confirmed. In vitro, CPNPs significantly increased the uptake of DOX and enhanced the cytotoxicity of DOX to tumour cells. More importantly, DOX@CPNPs strongly reversed drug resistance in three different types of cancer cells, exhibiting significant anticancer effects. Collectively, this study presents the easy preparation of nanomedicines that respond to multiple stimuli, which highlights the advantages of Schiff base-based nanomedicines for cancer therapy and reversing chemoresistance.

A Shapable Alginate Hydrogel Resolving the Conflicts between Multifunctionality and Fabrication Simplicity.

Alginate is a naturally derived biocompatible polymer widely used as a drug or food adjuvant. However, its usage as a biofunctional material has been confounded by the lack of shapable strategies. In this study, we report an easily applied ionic cross-linking strategy for fabricating shapable multifunctional SA-Ca(II) hydrogels employing the process of regulated diffusion. The fabrication proceeds in neutral solutions under ambient conditions. The obtained SA-Ca(II) hydrogel presents tunable moduli ranging from 4 to 30 kPa, resembling a series of human tissues. The tunable mechanical strength provides differentiation signals for stem cell polarization. The hydrogel film can lift a weight of 10 kg. The hydrogel can be prepared into various shapes and remains stable over one year upon rinsing in deionized water, but rapidly degrades in alginate lyase solutions. Subcutaneously embedded SA-Ca(II) hydrogels in mice show high biocompatibility and degrade over 4 weeks accompanied by hair follicle regeneration. Wearable protections as well as stimuli-responsive electronic circuits are then achieved, which not only protect the model body against high-temperature environments but also show warning signals when the protection loses effectiveness because of high temperatures. Overall, these results demonstrate that our SA-Ca(II) hydrogel offers appealing comprehensive functionalities from multifaceted perspectives, including mechanical strength, economic and environmental considerations, transparency, forming capability, biocompatibility, and conductivity.

Bioactive NAD+ Regeneration Promoted by Multimetallic Nanoparticles Based on Graphene-Polymer Nanolayers.

The concentration of nicotinamide adenine dinucleotide oxidized form (NAD+) changes during aging, and the production of NAD+ can significantly affect both health span and life span. However, it is still of great challenge to regenerate NAD+ from its precursors. Herein, we introduce a method to prepare multimetallic nanoparticles (including Au, Pt, Cu, and MgO) that can efficiently promote the conversion of NADH to NAD+. The nanoparticles are made by mixing reduced graphene oxide-polyethyleneimine-polyacrylic acid nano-films with metallic salts, where four different metal ions are reduced and grow at the surface of the nanolayers. The morphology, size, and growth rate of nanoparticles can be controlled by adding surfactants, applying an electric field, and so forth. Our multimetallic nanoparticles exhibit excellent catalytic performance that a complete conversion of NADH to NAD+ can be finished in 3 min without introducing additional oxygen. This work presents a way for the preparation of multimetallic nanoparticles to promote NAD+ regeneration, which shows great promise for the future design of high-performance materials for antiaging.

Synergistically Active Piezoelectrical H2 O2 Production Composite Film Achieved from a Catalytically Inert PVDF-HFP Matrix and SiO2 Fillers.

Local and decentralized H2 O2 production via a piezoelectrical process promises smart biological utilization as well as environmental benefits. However, stable, bio/environmentally safe, and easily applied H2 O2 generation materials are still lacking. Here, we report a novel flexible H2 O2 generation polymeric film composed of catalytically inert PVDF-HFP (Poly(vinylidene fluoride-co-hexafluoropropylene)) matrix and SiO2 nanoparticle fillers. The film is bio-/environmentally benign at resting states, but effectively produces H2 O2 upon ultrasonic motivation at a production rate of 492 µmol g SiO 2 - 1 in one hour. Experimental and simulation methods in combination indicate that the effective H2 O2 generation capabilities stem from the synergistic existence of piezoelectrical fields and the air-liquid-solid three-phase regions around the porous film. The chemical conversions are motivated by the adsorbed charges. The silicon hydroxyl groups properly stabilize the *OOH intermediate and facilitate the chemical conversions of 2e- ORR of ambient O2 . We expect the report to inspire H2 O2 piezoelectrical generation materials and promote the novel production strategies of H2 O2 as well as piezoelectrical functional materials.