[Bionic design, preparation and clinical translation of oral hard tissue restorative materials].

Oral diseases concern almost every individual and are a serious health risk to the population. The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour. Based on the principle of "learning from the nature", Deng Xuliang's group of Peking University School and Hospital of Stomatology has proposed a new concept of "microstructural biomimetic design and tissue adaptation of tooth/jaw materials" to address the worldwide problems of difficulty in treating dentine hypersensitivity, poor prognosis of restoration of tooth defects, and vertical bone augmentation of alveolar bone after tooth loss. The group has broken through the bottleneck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects, and invented key technologies such as crystalline/amorphous multi-level assembly, ion-transportation blocking, and multi-physical properties of the micro-environment reconstruction, etc. The group also pioneered the cationic-hydrogel desensitizer, digital stump and core integrated restorations, and developed new crown and bridge restorative materials, gradient functionalisation guided tissue regeneration membrane, and electrically responsive alveolar bone augmentation restorative membranes, etc. These products have established new clinical strategies for tooth/jaw defect repair and achieved innovative results. In conclusion, the research results of our group have strongly supported the theoretical improvement of stomatology, developed the technical system of oral hard tissue restoration, innovated the clinical treatment strategy, and led the progress of the stomatology industry.

A Multidrug Delivery Microrobot for the Synergistic Treatment of Cancer.

Multidrug combination therapy provides an effective strategy for malignant tumor treatment. This paper presents the development of a biodegradable microrobot for on-demand multidrug delivery. By combining magnetic targeting transportation with tumor therapy, it is hypothesized that loading multiple drugs on different regions of a single magnetic microrobot can enhance a synergistic effect for cancer treatment. The synergistic effect of using two drugs together is greater than that of using each drug separately. Here, a 3D-printed microrobot inspired by the fish structure with three hydrogel components: skeleton, head, and body structures is demonstrated. Made of iron oxide (Fe3 O4 ) nanoparticles embedded in poly(ethylene glycol) diacrylate (PEGDA), the skeleton can respond to magnetic fields for microrobot actuation and drug-targeted delivery. The drug storage structures, head, and body, made by biodegradable gelatin methacryloyl (GelMA) exhibit enzyme-responsive cargo release. The multidrug delivery microrobots carrying acetylsalicylic acid (ASA) and doxorubicin (DOX) in drug storage structures, respectively, exhibit the excellent synergistic effects of ASA and DOX by accelerating HeLa cell apoptosis and inhibiting HeLa cell metastasis. In vivo studies indicate that the microrobots improve the efficiency of tumor inhibition and induce a response to anti-angiogenesis. The versatile multidrug delivery microrobot conceptualized here provides a way for developing effective combination therapy for cancer.

Investigation of microplastics in sludge from five wastewater treatment plants in Nanjing, China.

Municipal wastewater treatment plants (WWTPs) have been regarded as the main receptors of microplastics in industrial and domestic wastewater. The excess sludge they generate is an important carrier for the microplastics to enter the environment. In China, relevant regional studies are still in an initial phase. In this work, microplastics in the sewage sludges at different sampling points of five WWTPs in Nanjing City (an important city in the Yangtze River basin) were investigated, including their abundance, morphology and chemical composition. Furthermore, the influence factors such as population density, economic development level, wastewater source and treatment process were also discussed. The analysis results through optical microscope and FT-IR showed that the detected microplastics were divided into fragments, films, fibers and granules. Their chemical component reached up to 19 species, including small amounts of petroleum resins which was scarcely detected in other studies. Wastewater source was the primary factor influencing the microplastic abundance and size in sludge. And the microplastic shape and chemical components were closely related to the industrial type. Furthermore, because the removal effect on the microplastics with different morphologies were varied with the treatment process, the preliminary suggestions on the technology for particular wastewater were proposed. This study provides partial regional data and analysis for the microplastics contained in the sludge of WWTPs, expecting to provide a certain theoretical support for the operations management of WWTPs and standardized sludge treatment.

Dysfunction of the 4-coumarate:coenzyme A ligase 4CL4 impacts aluminum resistance and lignin accumulation in rice.

The root cell wall is the first and primary target of aluminum (Al) toxicity. Monocots such as rice (Oryza sativa) can accumulate appreciable levels of hydroxycinnamic acids (HCAs) to modify and cross-link hemicellulose and/or lignin of the cell wall. Nevertheless, it is unclear whether this HCA-mediated modification of the cell wall is important for Al accumulation and resistance. We previously isolated and characterized a rice ral1 (resistance to aluminum 1) mutant that shows enhanced Al resistance. In this study, we cloned RAL1 and found that it encodes the 4-coumarate:coenzyme A ligase 4CL4, an enzyme putatively involved in lignin biosynthesis. Mutation of RAL1/4CL4 reduces lignin content and increases the accumulation of its substrates 4-coumaric acid (PA) and ferulic acid (FA). We demonstrate that altered lignin accumulation is not required for the enhanced Al resistance in ral1/4cl4 mutants. We found that the increased accumulation of PA and FA can reduce Al binding to hemicellulose and consequently enhance Al resistance in ral1/4cl4 mutants. Al stress is able to trigger PA and FA accumulation, which is likely caused by the repression of the expression of RAL1/4CL4 and its homologous genes. Our results thus reveal that Al-induced PA and FA accumulation is actively and positively involved in Al resistance in rice through the modification of the cell wall and thereby the reduced Al binding to the cell wall.

The effect of low-level laser therapy as an adjunct to periodontal surgery in the management of postoperative pain and wound healing: a systematic review and meta-analysis.

The meta-analysis and systematic review aimed to evaluate the effect of low-level laser therapy (LLLT) as an adjunct to periodontal surgery in the management of postoperative pain and wound healing. An electronic search in 4 databases (PubMed, Embase, Cochrane, and OpenGrey) was conducted for randomized clinical trials reporting the effectiveness of LLLT used as an adjunct to periodontal surgery to alleviate pain and accelerate wound healing compared with surgery alone. Finally, 13 studies were eligible and included. The results showed a significant difference of pain relief between groups at day 3 post-surgery, whereas no difference was found at day 7. Moreover, a significant reduction was observed in the mean analgesic intake during the first week in the LLLT group. On day 14, the adjunctive use of LLLT showed significantly faster re-epithelialization and better wound healing in palatal donor sites following free gingival graft procedures. Based on the results, LLLT used as an adjunct to periodontal surgery positively influenced postsurgical pain control. Low power (≤ 500 mW) combined with energy density ≥ 5 J/cm2 might be more appropriate for postoperative pain relief. Moreover, adjunctive LLLT to free gingival grafts could significantly accelerate wound healing of palate sites at early healing phase. Multicenter studies using different LLL parameters without postsurgical analgesics are needed to determine optimal laser settings.

The effect of drug dose and duration of adjuvant Amoxicillin-plus-Metronidazole to full-mouth scaling and root planing in periodontitis: a systematic review and meta-analysis.

OBJECTIVES: The aim is to explore the optimal drug dose and duration of adjunctive Amoxicillin-plus-Metronidazole (AMX/MET) to full-mouth scaling and planing (FMSRP) in periodontitis. METHODS: An electronic search in four databases and manual search in four journals were conducted for randomised clinical trials comparing AMX/MET adjunct to FMSRP with FMSRP alone for at least 3 months. RESULTS: Eleven studies were eligible and included. The primary outcome was clinical attachment level (CAL) gain, the secondary outcomes were periodontal pocket depth (PPD) reduction and adverse events. Our results showed a beneficial effect of adjunctive AMX/MET with higher drug dose to FMSRP for CAL gain and PPD reduction at 3 months, and the benefit remained stable at 6 months. However, minimal difference among three-seven-and ten-day drug duration was observed. In addition, the risk difference of adverse events was minimal between two groups. CONCLUSION: FMSRP adjunct to a high drug dose of 500/500 mg of AMX/MET showed a significant and stable improvement on 6-month follow-up period. No decision for drug duration could be made due to limited evidence. CLINICAL RELEVANCE: On 6-month follow-up, higher dose of AMX/MET adjunct to FMSRP could provide a stable clinical effect. No recommendation for drug duration could be made.

Epidemiological and clinical characteristics of severe hand-foot-and-mouth disease (HFMD) among children: a 6-year population-based study.

BACKGROUND: Hand-foot-and-mouth disease (HFMD) is considered to be self-limited, however, severe HFMD is a deadly threat for children worldwide, therefore, it is essential to define the clinical and epidemiologic characteristics of children with severe HFMD and identify the risk factors of death. METHODS: Between 2013 and 2018, children who diagnosed with severe HFMD from Chongqing, China were enrolled in this population-based study. A total of 459 severe HFMD children cases were identified during the study period, including 415 survivors and 44 fatal cases. Demographic, geographical, epidemiological and clinical data of the cases were acquired and analyzed. RESULTS: Risk factors of the death because of severe HFMD children included female, aged 1 ~ 3 years, enterovirus 71 infection, falling ill in winter, more than one children in home, being taken care of by grandparents, the caregivers' education not more than 9 years, having fever more than 3 days, consciousness disorders, general weakness, vomiting, general weakness, abnormal pupillary light reflex, repeated cough, tachypnea, moist rales, white frothy sputum, pink frothy sputum, and cyanosis on lips or the whole body, tachycardia, arrhythmia, cold limbs, pale complexion, weakened pulse. (all p < 0.05). Spatial-temporal analysis detected high-value clusters, the most likely cluster located at rural countries in the northern parts of Chongqing, from January, 2015 to July, 2017. (p < 0.01). Besides, some urban districts were also found high incidence of severe HFMD cases according to the incidence maps. CONCLUSIONS: The detection of clinical risk factors and the temporal, spatial and socio-demographic distribution epidemiological characteristics of severe HFMD contribute to the timely diagnosis and intervention, the results of this study can be the reference of further clinical and public health practice.

Study on the adsorption of polystyrene microplastics by three-dimensional reduced graphene oxide.

In this paper, a study on the removal of imitated polystyrene (PS) microplastics in water was carried out based on the adsorption capacity of three-dimensional reduced graphene oxide (3D RGO). Scanning electron microscopy and X-ray diffractometry characterization showed that the freeze-dried 3D RGO formed a distinct porous spatial structure. Different experimental parameters, such as pH, ion concentration (C0), contact time (t), and temperature (T), were studied to investigate the PS microplastic adsorption performance of 3D RGO. The adsorption mechanism was mainly attributed to the strong π-π interaction between the carbon ring of 3D RGO and the benzene ring of PS microplastics. Sorption kinetic and isothermal data were obtained by the well-fitted Langmuir adsorption isotherm model and pseudo-second-order kinetic model. Furthermore, the result of thermodynamic analysis showed that the adsorption of PS microplastics was a spontaneous endothermic process. Under the optimal conditions of pH = 6, C0 = 600 mg/L, t = 120 min, and T = 26 °C, the maximum adsorption capacity of the prepared 3D RGO on PS microplastics was 617.28 mg/g. Furthermore, this method exhibited good feasibility in tap water and lake water.

Adjunctive subgingival application of Chlorhexidine gel in nonsurgical periodontal treatment for chronic periodontitis: a systematic review and meta-analysis.

BACKGROUND: Subgingival applications of chlorhexidine (CHX) gel are commonly used as an adjunct in nonsurgical periodontal treatment (NSPT) for chronic periodontitis (CP). However, there is lack of systematic review and meta-analysis justifying the effects of adjunctive CHX gel on clinical outcomes. The objective of this meta-analysis was to evaluate the efficacy of adjunctive subgingival administration of CHX gel in NSPT compared to NSPT alone for CP. METHODS: An electronic search of four databases and a manual search of four journals were conducted up to August 2019. Only randomized controlled trials reporting on the clinical outcomes of subgingival use of CHX gel adjunct to scaling and root planing (SRP), as compared to SRP alone or with placebo, for at least 3 months were included. Primary outcomes were probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain at 3 and 6 months, when data on at least three studies were obtained. RESULTS: Seventeen studies were included for qualitative analysis and seven studies for quantitative analysis (four studies for the application of CHX gel adjunct to SRP at selected sites with at least pocket depth ≥ 4 mm and three studies for comparison of full-mouth disinfection (FMD) with subgingival use of CHX gel and full-mouth scaling and root planing (FMSRP). For subgroups, the clinical outcomes between adjunctive use of Xanthan-based CHX gel (XAN-CHX gel) and CHX gel were analyzed. Results indicated a significant improvement of PPD reduction following local adjunctive administration of XAN-CHX gel for SRP at selected sites (MD: 0.15 mm). However, no difference was found in CAL gain. Moreover, no significant difference was observed in PPD and CAL at both 3 and 6 months post-treatment between FMD and FMSRP. CONCLUSION: Adjunctive subgingival administration of XAN-CHX gel at individual selected sites in NSPT appears to provide slight benefits in PPD reduction compared to NSPT alone for CP. Due to the lack of high-quality studies, further studies with larger sample sizes and strict standards are needed to confirm the conclusions.

Smart hydrogels with high tunability of stiffness as a biomimetic cell carrier.

Human tissues are sophisticated ensembles of various distinct cell types encapsulated in the biomechanical cues of the extracellular matrix. It has been known matrix stiffness plays a pivot role in cellular events and tissue-scale biological processes. Thus, materials that can mimic mechanical environments of tissues in vitro and possess wide, physiologically relevant elasticity are highly desirable. Hydrogels provide a good cell platform to mimic native cellular environment. However, the limited stiffness tunability, and hinders the efforts to reproduce the biomechanical microenvironment of many in vivo progresses. These problems have been addressed by the recently emerged great quantity of exquisitely designed smart hydrogels. Smart hydrogels that respond sensitively to external stimuli are good choices due to the convenience in regulating their mechanical properties. In this review, we summarize the latest progress in the development of stimuli-responsive hydrogels as a cell carrier (platform for cell culture) which spans a wide range of stiffness. Different kinds of smart hydrogels corresponding to various stimuli, including pH, temperature, light, metal ions, and forces, are introduced and their stiffness modulation through physicochemical procedures are reported.

Pre-augmentation soft tissue expansion improves scaffold-based vertical bone regeneration - a randomized study in dogs.

OBJECTIVE: Soft tissue (ST) dehiscence with graft exposure is a frequent complication of vertical augmentation. Flap dehiscence is caused by failure to achieve tension-free primary wound closure and by the impairment of flap microcirculation due to surgical trauma. Soft tissue expansion (STE) increases ST quality and quantity prior to reconstructive surgery. We hypothesized that flap preconditioning using STE would reduce the incidence of ST complications after bone augmentation and that optimized ST healing would improve the outcome of bone regeneration. MATERIALS AND METHODS: Self-filling tissue expanders were implanted in mandibular bone defects in ten beagle dogs. After expansion, alloplastic scaffolds were placed for vertical bone augmentation in STE sites and in control sites without STE pre-treatment. ST flap microcirculation was analysed using laser Doppler flowmetry. The incidence of graft exposures was evaluated after 2 weeks. Bone formation was assessed after 2 months, using histomorphometry and immunohistochemistry. RESULTS: Test sites showed significantly less impairment of perfusion and faster recovery of microcirculation after bone augmentation. Furthermore, no flap dehiscences occurred in STE sites. Bone regeneration was found in both groups; however, significantly greater formation of new bone was detected in test sites with preceding STE. CONCLUSIONS: Preconditioning using STE improved ST healing and bone formation after vertical augmentation. The combination of STE and the subsequent placement of alloplastic scaffolds may facilitate the reconstruction of severe bone defects.

Seasonal modeling of hand, foot, and mouth disease as a function of meteorological variations in Chongqing, China.

Hand, foot, and mouth disease (HFMD) is an enterovirus-induced infectious disease, mainly affecting children under 5 years old. Outbreaks of HFMD in recent years indicate the disease interacts with both the weather and season. This study aimed to investigate the seasonal association between HFMD and weather variation in Chongqing, China. Generalized additive models and distributed lag non-linear models based on a maximum lag of 14 days, with negative binomial distribution assumed to account for overdispersion, were constructed to model the association between reporting HFMD cases from 2009 to 2014 and daily mean temperature, relative humidity, total rainfall and sun duration, adjusting for trend, season, and day of the week. The year-round temperature and relative humidity, rainfall in summer, and sun duration in winter were all significantly associated with HFMD. An inverted-U relationship was found between mean temperature and HFMD above 19 °C in summer, with a maximum morbidity at 27 °C, while the risk increased linearly with the temperature in winter. A hockey-stick association was found for relative humidity in summer with increasing risks over 60%. Heavy rainfall, relative to no rain, was found to be associated with reduced HFMD risk in summer and 2 h of sunshine could decrease the risk by 21% in winter. The present study showed meteorological variables were differentially associated with HFMD incidence in two seasons. Short-term weather variation surveillance and forecasting could be employed as an early indicator for potential HFMD outbreaks.

Early Healing Events after Periodontal Surgery: Observations on Soft Tissue Healing, Microcirculation, and Wound Fluid Cytokine Levels.

Early wound healing after periodontal surgery with or without enamel matrix derivative/biphasic calcium phosphate (EMD/BCP) was characterized in terms of soft tissue closure, changes of microcirculation, and expression of pro- and anti-inflammatory cytokines in gingival crevicular fluid/wound fluid (GCF/WF). Periodontal surgery was carried out in 30 patients (18 patients: application of EMD/BCP for regeneration of bony defects; 12 patients: surgical crown lengthening (SCL)). Healthy sites were observed as untreated controls. GCF/WF samples were collected during two post-surgical weeks. Flap microcirculation was measured using laser Doppler flowmetry (LDF). Soft tissue healing was evaluated after two weeks. GCF/WF levels of interleukin 1ß (IL-1ß), tumour necrosis factor (TNF-α), IL-6, and IL-10 were determined using a multiplex immunoassay. Surgery caused similar reductions of flap microcirculation followed by recovery within two weeks in both EMD/BCP and SCL groups. GCF/WF and pro-inflammatory cytokine levels were immediately increased after surgery, and returned only partially to baseline levels within the two-week observation period. Levels of IL-10 were temporarily reduced in all surgical sites. Flap dehiscence caused prolonged elevated levels of GCF/WF, IL-1ß, and TNF-α. These findings show that periodontal surgery triggers an immediate inflammatory reaction corresponding to the early inflammatory phase of wound healing, and these inflammation measures are temporary in case of maintained closure of the flap. However, flap dehiscence causes prolonged inflammatory exudation from the periodontal wound. If the biological pre-conditions for periodontal wound healing are considered important for the clinical outcome, care should be taken to maintain primary closure of the flap.

Improvement of microcirculation and wound healing in vertical ridge augmentation after pre-treatment with self-inflating soft tissue expanders - a randomized study in dogs.

OBJECTIVES: We investigated the effect of soft tissue expansion (STE) on vertical ridge augmentation with regard to the incidence of wound dehiscences and the impairment of microcirculation in dogs, and the applicability of laser Doppler flowmetry (LDF) to explore the relation between microcirculation and wound healing. MATERIAL AND METHODS: Bone defects were created on both mandibular sides in ten beagle dogs by extraction of premolars and removal of bone. Six weeks later, self-filling tissue expanders were implanted in randomly assigned test sites. After 5 weeks of expansion, vertical augmentation was carried out in test and control sites using calvarial onlay grafts side by side with granular biphasic calcium phosphate covered with a resorbable polyethylene glycol membrane. Microcirculation was evaluated with laser Doppler flowmetry (LDF). The incidence of wound dehiscences was evaluated after 2 weeks. The validity of LDF to predict dehiscences was evaluated by construction of receiver operating characteristic (ROC) curves. RESULTS: After augmentation, test sites showed significantly better perfusion than control sites without preceding STE (P = 0.012). Three days after surgery, perfusion was still significantly decreased in control sites (P = 0.005), while microcirculation in test sites had returned to pre-surgical levels. After 2 weeks, healing in test sites was good, whereas eight dehiscences were found in control sites (P = 0.002). ROC curves showed that microcirculation levels immediately after augmentation surgery significantly predicted subsequent wound dehiscences (AUC = 0.799, CI 0.642-0.955, P = 0.006). CONCLUSIONS: Laser Doppler flowmetry is suitable for evaluation of soft tissue microcirculation after ridge augmentation. STE reduced the impairment of microcirculation caused by vertical ridge augmentation and decreased the incidence of wound dehiscences in the investigated animal model.

Submucosal implantation of soft tissue expanders does not affect microcirculation.

AIM: To investigate the effect of submucosal implantation of self-filling osmotic tissue expanders on mucosal microcirculation. MATERIAL AND METHODS: In ten beagle dogs, all premolars were extracted on both sides of the mandible. Tooth-supporting bone and excess soft tissue were removed to mimic a severely resorbed edentulous ridge. Six weeks later, tissue expanders with 0.7 ml final volume were implanted into a submucosal pouch at randomly selected test sites, while contralateral sites served as untreated controls. Microcirculation was assessed in perfusion units (PU) before surgery, after local anaesthesia, directly after surgery, and after 1 and 3 days, using Laser Doppler flowmetry. RESULTS: Local anaesthesia caused a significant decrease of blood flow from baseline (zero) to -6.4 PU (median; Q1 -10.5; Q3 -0.9; P = 0.006); however, no additional significant decrease was recorded after completion of surgery. Blood flow showed significant increases to -3.6 PU (median; Q1 -11.3, Q3 2.1; P = 0.02) and -4.0 PU (median; Q1 -9.2, Q3 1.1; P = 0.013) after 1 and 3 days, respectively, when compared to the measurements obtained after application of local anaesthesia and completion of surgery. Blood flow had returned to unimpaired baseline levels 1 day after surgery (P > 0.05). CONCLUSIONS: Submucosal implantation of self-filling osmotic tissue expanders results in only momentary disturbance of microcirculation. The minor impairment of perfusion may explain the consistently good outcomes of submucosal implantation of these tissue expanders.

The Effect of Local Application of Tea Tree Oil Adjunctive to Daily Oral Maintenance and Nonsurgical Periodontal Treatment: A Systematic Review and Meta-Analysis of Randomised Controlled Studies.

PURPOSE: To evaluate the efficacy of the adjunctive use of tea tree oil (TTO) for dental plaque control and nonsurgical periodontal treatment (NSPT). MATERIALS AND METHODS: Three electronic databases were searched from 2003. The reference lists of the included articles and relevant reviews were also manually searched. Randomised controlled trials reporting the clinical outcomes of the topical use of TTO as an adjunct to daily oral hygiene or scaling and root planing (SRP) were included. Regarding the use of TTO as an adjunctive to daily oral hygiene, the primary outcome was plaque index (PI) reduction. Regarding the use of TTO as an adjunctive to SRP, probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain were the primary outcomes. The secondary outcomes were adverse events. RESULTS: Eleven studies were included for qualitative analysis, 9 studies were included for quantitative analysis, and 6 studies were included to examine the application of TTO mouthwash as an adjunctive to daily oral hygiene. In addition, three studies were included to analyse the subgingival use of TTO adjunctive to SRP at selected sites. The results indicated a nonsignificant improvement in PI reduction in the TTO mouthwash group compared with placebo. The incidence of adverse events was statistically significantly greater in the CHX group than in the TTO group. For subgingival use of TTO adjunctive to SRP, beneficial effects were observed in the TTO group compared with SRP alone in terms of PPD and CAL at both three and six months post-treatment. However, an unpleasant taste was reported in three out of four studies. CONCLUSION: There is a lack of strong evidence to support the beneficial effects of TTO. Studies with larger sample sizes and standardised evaluation criteria are needed to further demonstrate the clinical relevance of TTO.

Recent advances in cellulose microgels: Preparations and functionalized applications.

Microgels are soft, deformable, permeable, and stimuli-responsive microscopic polymeric particles that are now emerging as prospective multifunctional soft materials for delivery systems, interface stabilization, cell cultures and tissue engineering. Cellulose microgels are emerging biopolymeric microgels with unique characteristics such as abound hydroxyl structure, admirable designability, multiscale pore network and excellent biocompatibility. This review summarizes the fabrication strategies for microgel, then highlights the fabrication routes for cellulose microgels, and finally elaborates cellulose microgels' bright application prospects with unique characteristics in the fields of controlled release, interface stabilization, coating, purification, nutrition/drug delivery, and bio-fabrication. The challenges to be addressed for further applications and considerable scope for development in future of cellulose microgels are also discussed.

Chitosan Hydrogel-Delivered ABE8e Corrects PAX9 Mutant in Dental Pulp Stem Cells.

Hypodontia (dental agenesis) is a genetic disorder, and it has been identified that the mutation C175T in PAX9 could lead to hypodontia. Cas9 nickase (nCas9)-mediated homology-directed repair (HDR) and base editing were used for the correction of this mutated point. This study aimed to investigate the effect of HDR and the base editor ABE8e in editing PAX9 mutant. It was found that the chitosan hydrogel was efficient in delivering naked DNA into dental pulp stem cells (DPSCs). To explore the influence of the C175T mutation in PAX9 on the proliferation of DPSCs, hydrogel was employed to deliver PAX9 mutant vector into DPSCs, finding that the PAX9-containing C175T mutation failed to promote the proliferation of DPSCs. Firstly, DPSCs stably carrying PAX9 mutant were constructed. Either an HDR or ABE8e system was delivered into the above-mentioned stable DPSCs, and then the correction efficiency using Sanger sequencing and Western blotting was determined. Meanwhile, the ABE8e presented significantly higher efficiency in correcting C175T compared with HDR. Furthermore, the corrected PAX9 presented enhanced viability and differentiation capacity for osteogenic and neurogenic lineages; the corrected PAX9 even possessed extremely enhanced transcriptional activation ability. In summary, this study has powerful implications for studies into base editors, chitosan hydrogel, and DPSCs in treating hypodontia.

Doxorubicin-Loaded Liposome with the Function of "Killing Two Birds with One Stone" against Glioma.

The blood-brain barrier (BBB) continues to be one of the main clinical obstacles in the treatment of glioma. Current chemotherapies always bring many different side effects, some even permanent. To date, nanomaterial-based vehicles have shown great potential in treating glioma. Herein, we developed a dual targeting liposomal delivery vector loaded with the anticancer drug doxorubicin (DOX) to treat glioma. SS31, a small peptide, has shown dual targeting effects of penetrating the BBB and specifically targeting mitochondria. In this study, a new liposomal delivery system, LS-DOX, was prepared by modifying DOX-loaded liposomes with SS31 for the treatment of in situ glioma. The liposomes demonstrated a high drug encapsulation rate and drug-loading capacity, satisfactory biocompatibility, high glioma accumulation ability, and good stability in vitro. Experimental results showed that the liposomes could effectively cross the BBB and target gliomas, and mitochondria-targeting of SS31 enhances cell uptake. In addition, the liposomes showed a good therapeutic effect on nude mice with glioma in situ with no obvious toxicity and side effects. Therefore, the present research will provide a novel alternative and reference for the effective treatment of glioma.

Non-linear association between daily mean temperature and children's hand foot and mouth disease in Chongqing, China.

Chongqing was seriously affected by hand, foot, and mouth disease (HFMD), but the relationships between daily mean temperature and the incidence of HFMD remain unclear. This study used distributed lag nonlinear model to evaluate the effect of daily mean temperature on the incidence of HFMD in children aged < 5 years in Chongqing. Daily HFMD data from 2012 to 2019 in Chongqing were retrieved from the notifiable infectious disease surveillance system. A total of 413,476 HFMD cases aged < 5 years were reported in Chongqing from 2012 to 2019. The exposure-response curve of daily mean temperature and daily HFMD cases was wavy-shaped. The relative risks (RRs) increased as daily mean temperature below 5.66 °C or above 9.43 °C, with two peaks at 16.10 °C and 26.68 °C. The RRs reached the highest when the daily mean temperature at 26.68 °C on the current day (RR = 1.20, 95% CI 1.09-1.32), followed by the daily mean temperature at 16.10 °C at lag 5 days (RR = 1.07, 95% CI 1.05-1.08). The RRs for girls and daycare children were much higher than those for boys and scattered children, respectively. Taken together, daily mean temperature has strong effect on HFMD in children aged < 5 years old in Chongqing, particularly for girls and daycare children.