Impact of different types of temporomandibular disorders on jaw functional limitation and psychological distress in orthodontic patients.

BACKGROUND: Some orthodontic patients are associated with temporomandibular joint disorders (TMDs), and the differences between jaw function and psychological states in orthodontic patients with different types of TMDs remain unknown. OBJECTIVE: This cross-sectional study aimed to investigate the prevalence of different types of TMDs in orthodontic patients and to evaluate the relationship between different types of TMDs and jaw functional limitation and psychological distress in orthodontic patients. METHODS: A questionnaire was sent to patients willing to participate in this survey, which included questions about the demographic characteristics of the participants, the five TMD symptoms (5Ts) of the Diagnostic Criteria for TMDs, the Jaw Functional Limitation Scale-8 (JFLS-8) and the Patient Health Questionnaire for Depression and Anxiety (PHQ-4). The subjects were divided into three groups: painful TMDs (PT), non-painful TMDs (NPT), and TMD-free according to whether they had TMDs and its subtypes. RESULTS: A total of 670 valid questionnaires were collected from 182 males and 488 females. The prevalence of TMDs was 35.4%, of which the prevalence of PT was 11.8% and the prevalence of NPT was 23.6%. The median JLFS-8 score of TMD patients was significantly higher than TMD-free, and PT patients were significantly higher than NPT (p = .026). After adjusting for confounding factors, the jaw function and psychological states of PT patients and NPT patients were worse than those of the TMD-free group. CONCLUSIONS: Among the orthodontic patients surveyed, more than one-third had TMDs and the prevalence of PT was lower than NPT. Having TMDs is associated with more severe jaw functional limitation, and PT patients were more serious than NPT patients. At the same time, the psychological states of TMDs patients were also worse.

Distinctive Adsorption Mechanism and Kinetics of Immunoglobulin G on a Nanoscale Polymer Surface.

Elucidation of protein adsorption beyond simple polymer surfaces to those presenting greater chemical complexity and nanoscopic features is critical to developing well-controlled nanobiomaterials and nanobiosensors. In this study, we repeatedly and faithfully track individual proteins on the same nanodomain areas of a block copolymer (BCP) surface and monitor the adsorption and assembly behavior of a model protein, immunoglobulin G (IgG), over time into a tight surface-packed structure. With discrete protein adsorption events unambiguously visualized at the biomolecular level, the detailed assembly and packing states of IgG on the BCP nanodomain surface are subsequently correlated to various regimes of IgG adsorption kinetic plots. Intriguing features, entirely different from those observed from macroscopic homopolymer templates, are identified from the IgG adsorption isotherms on the nanoscale, chemically varying BCP surface. They include the presence of two Langmuir-like adsorption segments and a nonmonotonic regime in the adsorption plot. Via correlation to time-corresponding topographic data, the unique isotherm features are explained with single biomolecule level details of the IgG adsorption pathway on the BCP. This work not only provides much needed, direct experimental evidence for time-resolved, single protein level, adsorption events on nanoscale polymer surfaces but also signifies mutual linking between specific topographic states of protein adsorption and assembly to particular segments of adsorption isotherms. From the fundamental research viewpoint, the correlative ability to examine the nanoscopic surface organizations of individual proteins and their local as well as global adsorption kinetic profiles will be highly valuable for accurately determining protein assembly mechanisms and interpreting protein adsorption kinetics on nanoscale surfaces. Application-wise, such knowledge will also be important for fundamentally guiding the design and development of biomaterials and biomedical devices that exploit nanoscale polymer architectures.

Associations among Orthodontic History, Psychological Status, and Temporomandibular-Related Quality of Life: A Cross-Sectional Study.

Objectives: This cross-sectional study aimed to evaluate the associations among orthodontic history, psychological status, and temporomandibular-related quality of life. Methods: A questionnaire was developed and distributed to students in a local college, containing questions about demographic information, the Patient Health Questionnaire-4 (PHQ-4), the Fonseca anamnestic index, and the Oral Health Impact Profile for Temporomandibular Disorders (OHIP-TMD). The respondents were divided into with orthodontic history (OS) group and without OS group. Binary logistic regression and multiple linear regression were performed for statistical analysis. Results: A total of 531 valid questionnaires were collected, covering 161 participants with OS and 370 participants without OS. No statistically significant differences were observed in the scores of PHQ-4 between the two groups. There was statistical difference in the prevalence of TMD (with OS group, 54.66%; without OS group, 40.81%) and the mean value ( ± standard deviations) of the scores of OHIP-TMD (with OS group, 9.64 ± 12.36; without OS group, 6.64 ± 10.79) (p < 0.05). After adjusting confounding factors, participants with OS have worse temporomandibular-related quality of life and a higher risk of having TMD than the participants without OS. Conclusions: Orthodontic history was related with the higher prevalence of TMD and worse temporomandibular-related quality of life, but not related with psychological distress, and the cause-and-effect relationship needs further exploration.

Pnictogens in medicinal chemistry: evolution from erstwhile drugs to emerging layered photonic nanomedicine.

Pnictogens (the non-metal phosphorus, metalloids arsenic and antimony, and metal bismuth) possess diverse chemical characteristics that support the formation of extended molecular structures. As witnessed by the centuries-old (and ongoing) clinical utilities, pnictogen-based compounds have secured their places in history as "magic bullet" therapeutic drugs in medicinal contexts. Moreover, with the development of recent metalloproteomics and bio-coordination chemistry, the pnictogen-based drugs functionally binding to proteins/enzymes in biological systems have been underlaid for "drug repurposing" with promising opportunities. Furthermore, advances in the modern materials science and nonotechnology have stimulated a revolution in other newly discovered forms of pnictogens-phosphorene, arsenene, antimonene, and bismuthine (layered pnictogens). Based on their favorable optoelectronic properties, layered pnictogens have shown dramatic superiority as emerging photonic nanomedicines for the treatment of various diseases. This tutorial review outlines the history and mechanism of action of ancient pnictogen-based drugs (e.g., arsenical compounds in traditional Chinese medicine) and their repurposing into modern therapeutics. Then, the revolutionary use of emerging layered pnictogens as photonic nanomedicines, alongside assessments of their in vivo biosafety, is discussed. Finally, the challenges to further development of pnictogens are set forth and insights for further exploration of their appealing properties are offered. This tutorial review may also provide some deep insights into the fields of integrated traditional Chinese and Western medicines from the perspective of materials science and nanotechnology.

Recurrent retinal detachment after pars plana vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment.

BACKGROUND: The recurrence of retinal detachment following rhegmatogenous retinal detachment (RRD) is a relatively common complication that can lead to reduced visual acuity and requires further surgery. The purpose of this study was to investigate the risk factors and visual outcomes of recurrent RRD following pars plana vitrectomy (PPV) with silicone oil tamponade for primary RRD. METHODS: This was a retrospective follow-up study of 343 eyes that underwent initial PPV surgery with silicone oil tamponade for primary RRD. Patients were divided into a recurrence group and a reattachment group. The main outcome measures included causative factors, visual outcomes related to the recurrence of RRD, and the perioperative factors most affecting the recurrence of RRD. RESULTS: After retinal reattachment, we observed RRD recurrence after PPV for primary RRD in 42 out of 343 eyes (12.2%) during the follow-up period. Most causes of recurrence (69%) occurred within 6 months of surgery. Multivariate logistic regression analysis showed that a PVR ≥ Grade C (odds ratio [OR]: 4.015; 95% confidence interval [CI] 1.721-9.367; P = 0.001) was a significant predictor for the development of recurrent RRD. Compared with the reattachment group, the recurrence group exhibited a significant decline in best-corrected visual acuity (BCVA) at the last follow-up visit (P = 0.000). Eyes with PVR prior to primary surgery, or at the diagnosis of re-detachment, showed a worse final BCVA. CONCLUSIONS: Our analysis shows that the predominant risk factor for the recurrence of RRD is a PVR ≥ Grade C. PVR prior to primary surgery, or at the diagnosis of re-detachment, was also shown to limit the recovery of final visual acuity.

Active targeting of orthotopic glioma using biomimetic liposomes co-loaded elemene and cabazitaxel modified by transferritin.

BACKGROUND: Effective treatment of glioma requires a nanocarrier that can cross the blood-brain barrier (BBB) to target the tumor lesion. In the current study, elemene (ELE) and cabazitaxel (CTX) liposomes were prepared by conjugating liposomes with transferrin (Tf) and embedding the cell membrane proteins of RG2 glioma cells into liposomes (active-targeting biomimetic liposomes, Tf-ELE/CTX@BLIP), which exhibited effective BBB infiltration to target glioma. RESULTS: The findings showed that Tf-ELE/CTX@BLIP was highly stable. The liposomes exhibited highly significant homologous targeting and immune evasion in vitro and a 5.83-fold intake rate compared with classical liposome (ELE/CTX@LIP). Bioluminescence imaging showed increased drug accumulation in the brain and increased tumor penetration of Tf-ELE/CTX@BLIP in orthotopic glioma model nude mice. Findings from in vivo studies indicated that the antitumor effect of the Tf-ELE/CTX@BLIP led to increased survival time and decreased tumor volume in mice. The average tumor fluorescence intensity after intravenous administration of Tf-ELE/CTX@BLIP was 65.2, 12.5, 22.1, 6.6, 2.6, 1.5 times less compared with that of the control, CTX solution, ELE solution, ELE/CTX@LIP, ELE/CTX@BLIP, Tf-ELE/CTX@LIP groups, respectively. Histopathological analysis showed that Tf-ELE/CTX@BLIP were less toxic compared with administration of the CTX solution. CONCLUSION: These findings indicate that the active-targeting biomimetic liposome, Tf-ELE/CTX@BLIP, is a promising nanoplatform for delivery of drugs to gliomas.

Stanene-Based Nanosheets for ß-Elemene Delivery and Ultrasound-Mediated Combination Cancer Therapy.

Ultrasound (US)-mediated sonodynamic therapy (SDT) has emerged as a superior modality for cancer treatment owing to the non-invasiveness and high tissue-penetrating depth. However, developing biocompatible nanomaterial-based sonosensitizers with efficient SDT capability remains challenging. Here, we employed a liquid-phase exfoliation strategy to obtain a new type of two-dimensional (2D) stanene-based nanosheets (SnNSs) with a band gap of 2.3 eV, which is narrower than those of the most extensively studied nano-sonosensitizers, allowing a more efficient US-triggered separation of electron (e- )-hole (h+ ) pairs for reactive oxygen species (ROS) generation. In addition, we discovered that such SnNSs could also serve as robust near-infrared (NIR)-mediated photothermal therapy (PTT) agents owing to their efficient photothermal conversion, and serve as nanocarriers for anticancer drug delivery owing to the inherent 2D layered structure. This study not only presents general nanoplatforms for SDT-enhanced combination cancer therapy, but also highlights the utility of 2D SnNSs to the field of nanomedicine.

The efficacy of analgesics in controlling orthodontic pain: a systematic review and meta-analysis.

BACKGROUND: Patients who had gone through orthodontic treatment experienced pain and discomfort which could be the highest-ranking reason for treatment disturbance or early termination. Thus, this review aimed to assess the efficacy of analgesics on the relief of pain in orthodontic treatment. METHODS: A computerized literature search was conducted in the databases of EMBASE (via OVID, 1974 to 2019 Week 50), MEDLINE (via OVID, 1946 to Dec 2019), the Cochrane Central Register of Controlled Trials (CENTRAL) (December 2019). The Cochrane Collaboration's Review Manager 5.3 software was applied in the present study. And methodological quality was evaluated by the Cochrane Risk of Bias Tool. RESULTS: We identified twelve publications including 587 patients in 19 randomized controlled trials. The results showed that the mean difference of naproxen in visual analogue scale (VAS) were - 1.45 (95% CI -2.72, - 0.19; P = .02), - 2.11 (95% CI -3.96, - 0.26; P = .03) and - 1.90 (95% CI -3.33, - 0.47; P = .009) in 2 h, 6 h and 24 h respectively. As for ibuprofen, the standard mean differences were - 1.10 (95% CI -1.49, - 0.71), - 1.63(95% CI -2.32, - 0.95) and - 1.34 (95% CI -2.12, - 0.55) at 2 h, 6 h, and 24 h, with the overall P values all < 0.001. The mean difference of acetaminophen is - 0.68, - 1.34, - 1.91 at three time points and the overall P values all < 0.01. CONCLUSIONS: This meta-analysis suggests that the use of analgesics is effective for patients in controlling orthodontic pain. Ibuprofen and naproxen are both of stable analgesic effects which could peak at 6 h, while the analgesic effect of acetaminophen increases steadily from 2 h through 24 h. Compared with ibuprofen and acetaminophen, naproxen shows a stronger analgesic effect either at 2 h or 6 h, and its effect lasts to 24 h.

The Preparation, Determination of a Flexible Complex Liposome Co-Loaded with Cabazitaxel and ß-Elemene, and Animal Pharmacodynamics on Paclitaxel-Resistant Lung Adenocarcinoma.

Paclitaxel is highly effective at killing many malignant tumors; however, the development of drug resistance is common in clinical applications. The issue of overcoming paclitaxel resistance is a difficult challenge at present. In this study, we developed nano drugs to treat paclitaxel-resistant lung adenocarcinoma. We selected cabazitaxel and ß-elemene, which have fewer issues with drug resistance, and successfully prepared cabazitaxel liposome, ß-elemene liposome and cabazitaxel-ß-elemene complex liposome with good flexibility. The encapsulation efficiencies of cabazitaxel and ß-elemene in these liposomes were detected by precipitation microfiltration and microfiltration centrifugation methods, respectively. Their encapsulation efficiencies were all above 95%. The release rates were detected by a dialysis method. The release profiles of cabazitaxel and ß-elemene in these liposomes conformed to the Weibull equation. The release of cabazitaxel and ß-elemene in the complex liposome were almost synchronous. The pharmacodynamics study showed that cabazitaxel flexible liposome and ß-elemene flexible liposome were relatively good at overcoming paclitaxel resistance on paclitaxel-resistant lung adenocarcinoma. As the flexible complex liposome, the dosage of cabazitaxel could be reduced to 25% that of the cabazitaxel injection while retaining a similar therapeutic effect. It showed that ß-elemene can replace some of the cabazitaxel, allowing the dosage of cabazitaxel to be reduced, thereby reducing the drug toxicity.

Improved Release of Celecoxib from High Drug Loading Amorphous Solid Dispersions Formulated with Polyacrylic Acid and Cellulose Derivatives.

Amorphous solid dispersions (ASDs) have been extensively exploited as a strategy for improving the dissolution performance of poorly water-soluble drugs. However, factors underpinning the observed dissolution profiles are not clearly understood, and the choice of polymeric carriers is largely empirical. In the current study, the dissolution performance of a high drug loading ASD containing the poorly water-soluble, anti-inflammatory agent, celecoxib, was optimized by using binary polymers combinations. Polyacrylic acid (PAA), a highly water-soluble polymer, was used to substantially increase the dissolution rate of the drug, while hydroxypropyl methyl cellulose (HPMC) or HPMC acetate succinate (HPMCAS) were added to stabilize the solid amorphous matrix against crystallization upon hydration, as well as to maintain supersaturation. Quantitative measurements of the impact of the polymers on the solution nucleation and growth rates of celecoxib revealed that, while the cellulose derivatives are effective nucleation inhibitors, it is more difficult to completely prevent crystal growth in solutions containing seed crystals, in particular at high supersaturations. Therefore, it is critical to prevent the formation of crystals in the dissolving matrix during dissolution. By using certain ratios of HPMC and PAA, both rapid release as well as crystallization inhibition could be achieved, even at high drug loadings. Utilizing combinations of polymers may therefore be useful to tailor release profiles while providing optimized crystallization inhibition.

Dissolution Performance of High Drug Loading Celecoxib Amorphous Solid Dispersions Formulated with Polymer Combinations.

PURPOSE: The aims of this study were twofold. First, to evaluate the effectiveness of selected polymers in inhibiting solution crystallization of celecoxib. Second, to compare the release rate and crystallization tendency of celecoxib amorphous solid dispersions (ASDs) formulated with a single polymer, or binary polymer combinations. METHODS: The effectiveness of polymers, polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMC) or HPMC acetate succinate (HPMCAS), in maintaining supersaturation of celecoxib solutions was evaluated by performing nucleation induction time measurements. Crystallization kinetics of ASD suspensions were monitored using Raman spectroscopy. Dissolution experiments were carried out under non-sink conditions. RESULTS: Pure amorphous celecoxib crystallized rapidly through both matrix and solution pathways. Matrix and solution crystallization was inhibited when celecoxib was molecularly mixed with a polymer, resulting in release of the drug to form supersaturated solutions. Cellulosic polymers were more effective than PVP in maintaining supersaturation. Combining a cellulosic polymer and PVP enabled improved drug release and stability to crystallization. CONCLUSIONS: Inclusion of an effective solution crystallization inhibitor as a minor component in ternary dispersions resulted in prolonged supersaturation following dissolution. This study shows the feasibility of formulation strategies for ASDs where a major polymer component is used to achieve one key property e.g. release, while a minor polymer component is added to prevent crystallization.

Molecular insights into substrate promiscuity of CotA laccase catalyzing lignin-phenol derivatives.

CotA laccases are multicopper oxidases known for promiscuously oxidizing a broad range of substrates. However, studying substrate promiscuity is limited by the complexity of electron transfer (ET) between substrates and laccases. Here, a systematic analysis of factors affecting ET including electron donor acceptor coupling (ΗDA), driving force (ΔG) and reorganization energy (λ) was done. Catalysis rates of syringic acid (SA), syringaldehyde (SAD) and acetosyringone (AS) (kcat(SAD) > kcat(SA) > kcat(AS)) are not entirely dependent on the ability to form phenol radicals indicated by ΔG and λ calculated by Density Functional Theory (SA < SAD ≈ AS). In determined CotA/SA and CotA/SAD structures, SA and SAD bound at 3.9 and 3.7 Å away from T1 Cu coordinating His419 ensuring a similar ΗDA. Abilities of substrate to form phenol radicals could mainly account for difference between kcat(SAD) and kcat(SA). Furthermore, substrate pocket is solvent exposed at the para site of substrate's phenol hydroxyl, which would destabilize binding of AS in the same orientation and position resulting in low kcat. Our results indicated shallow partially covered binding site with propensity of amino acids distribution might help CotA discriminate lignin-phenol derivatives. These findings give new insights for developing specific catalysts for industrial application.

Application of periodontal tissue regeneration combined with orthodontics in oral prosthodontics and its influence and significance on the expressions of IL-1ß, TNF-α and IL-5 in periodontal tissue.

The aim is to investigate the application of periodontal tissue regeneration combined with orthodontics in oral restoration, and explore its effect and significance on the expressions of Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and interleukin-5 (IL-5) in periodontal tissue. The patients in observation group were treated with orthodontics combined with periodontal tissue regeneration, and the control group was treated with periodontal tissue regeneration. The total effective rate, adverse reactions, recurrence rate and treatment satisfaction were compared. The masticatory function, language function, aesthetic level, VAS score, quality of life, gingival index (GI), plaque index (PLI), periodontal pocket probing depth (PD), sulcus bleeding index (SBI), IL-1ß, TNF-α and IL-5 levels were compared. The recurrence rate of observation group was lower than control group, while the treatment satisfaction was higher after treatment. After treatment, the scores of masticatory, language, aesthetics, physiological, social, emotional, cognitive, and emotional functions and overall health score were higher than before treatment. After treatment, the scores of masticatory and language functions, aesthetics and quality of life of observation group were significantly higher than control group. After treatment, the VAS score, GI, PLI, SBI, PD, IL-1ß, TNF-α and IL-5 levels were lower than before. The VAS score, GI, PLI, SBI, PD levels, IL-1ß, TNF-α and IL-5 levels of observation group were lower after treatment. Orthodontics combined with periodontal tissue regeneration can help improve the periodontal condition of patients with periodontitis, reduce inflammatory response, improve the level of efficacy and overall safety, and further improve patients' quality of life and treatment satisfaction.

[Oral health and hygiene behavior in chronic renal failure patients].

PURPOSE: To investigate the oral health and hygiene behavior of chronic renal failure(CRF) patients in Shenzhen, so as to provide basis for formulating education for them. METHODS: The history of renal failure, oral health status and oral health care behavior of 336 patients with chronic renal failure(CRF) in the hemodialysis center of Shenzhen Second People's Hospital were investigated by questionnaire and oral examinations. RESULTS: At an average, dialysis was required for 3.2 years. The main cause of renal failure was glomerulonephritis in 49.11% of patients, hypertensive kidney lesion in 19.35% and diabetic nephropathy in 15.77% of patients; 77.8% of them kept brushing teeth two or more than two times every day; 72.9% patients suffered from oral problems such as toothache in recent 12 months. The rate of visiting a dentist when having complaints was 21.7%. CONCLUSIONS: The state of oral health of CRF is worse than the general population of comparable age in China, while their hygiene behavior is better than the corresponding reference general population. However, their consciousness of dental treatment is poor. Therefore, health education for CRF patients should include knowledge about oral diseases complicated with CRF and correct medical philosophy.

Electrostatic assemblies of molecularly imprinted polymers on the surface of electrospun nanofiber membranes for the point-of-care detection of thiodiglycol, a sulfur mustard poisoning metabolic marker.

In this study, molecularly imprinted polymers (MIPs) were assembled on the surface of ethylene imine polymer (PEI)/poly(vinyl alcohol) (PVA) electrospun nanofiber membranes for the point-of-care testing (POCT) of thiodiglycol (TDG), a sulfur mustard poisoning metabolic marker, using concentrated gold nanoparticles (AuNPs) as the signal reporting units. The MIPs/PEI/PVA nanofiber membranes could capture TDG specifically through the recognition interaction between MIPs and TDG. Then, AuNPs were adsorbed onto the MIPs/PEI/PVA nanofiber membranes through the Au-S interaction between TDG and AuNPs to produce a visible red color. In order to improve the sensitivity, the silver-enhanced solutions were used to deepen the color of the nanofiber membranes and the software Image J was used to read the gray value as the signal response for subsequent analysis. There was a good linear relationship between the color change of the MIPs/PEI/PVA nanofiber membranes and the TDG concentration from 0.1 ng mL-1 to 1.0 µg mL-1, and the limit of detection was 38 pg mL-1. This method was applied for the selective detection of TDG in urine, showing great potential for the clinical diagnosis of mustard gas poisoning.

Facilitated transport of microplastics and nonylphenol in porous media with variations in physicochemical heterogeneity.

Nonylphenol (Noph) has garnered worldwide concern as a typical endocrine disruptor due to its toxicity, estrogenic properties, and widespread contamination. To better elucidate the interaction of Noph with ubiquitously existing microplastics (MPs) and the potential interdependence of their transport behaviors, batch adsorption and column experiments were conducted, paired with mathematical modeling. Compared with sand, MPs and soil colloids show stronger adsorption affinity for Noph due to the formation of hydrogen bonding and the larger numbers of interaction sites that are available on solid surfaces. Limited amount of soil-colloid coating on sand grains significantly influenced transport behaviors and the sensitivity to solution chemistry. These coatings led to a monotonic increase in Noph retention and a nonmonotonic MPs retention in single systems because of the altered physicochemical properties. The mobility of both MPs and Noph was enhanced when they coexisted, resulting from their association, increased electrostatic repulsion, and competition on retention sites. Limited release of MPs and Noph (under reduced ionic strength (IS) and increased pH) indicated strong interactions in irreversible retention. The retention and release of Noph were independent of IS and solution pH. A one-site model with a blocking term and a two-site kinetic model well described the transport of MPs and Noph, respectively. Our findings highlight the essential roles of coexisting MPs and Noph on their transport behaviors, depending on their concentrations, IS, and physicochemical properties of the porous media. The new knowledge from this study refreshes our understanding of the co-transport of MPs and organic contaminants such as Noph in the subsurface.

Opportunities and challenges for co-delivery nanomedicines based on combination of phytochemicals with chemotherapeutic drugs in cancer treatment.

The therapeutic limitations such as insufficient efficacy, drug resistance, metastasis, and undesirable side effects are frequently caused by the long duration monotherapy based on chemotherapeutic drugs. multiple combinational anticancer strategies such as nucleic acids combined with chemotherapeutic agents, chemotherapeutic combinations, chemotherapy and tumor immunotherapy combinations have been embraced, holding great promise to counter these limitations, while still taking including some potential risks. Nowadays, an increasing number of research has manifested the anticancer effects of phytochemicals mediated by modulating cancer cellular events directly as well as the tumor microenvironment. Specifically, these natural compounds exhibited suppression of cancer cell proliferation, apoptosis, migration and invasion of cancer cells, P-glycoprotein inhibition, decreasing vascularization and activation of tumor immunosuppression. Due to the low toxicity and multiple modulation pathways of these phytochemicals, the combination of chemotherapeutic agents with natural compounds acts as a novel approach to cancer therapy to increase the efficiency of cancer treatments as well as reduce the adverse consequences. In order to achieve the maximized combination advantages of small-molecule chemotherapeutic drugs and natural compounds, a variety of functional nano-scaled drug delivery systems, such as liposomes, host-guest supramolecules, supramolecules, dendrimers, micelles and inorganic systems have been developed for dual/multiple drug co-delivery. These co-delivery nanomedicines can improve pharmacokinetic behavior, tumor accumulation capacity, and achieve tumor site-targeting delivery. In that way, the improved antitumor effects through multiple-target therapy and reduced side effects by decreasing dose can be implemented. Here, we present the synergistic anticancer outcomes and the related mechanisms of the combination of phytochemicals with small-molecule anticancer drugs. We also focus on illustrating the design concept, and action mechanisms of nanosystems with co-delivery of drugs to synergistically improve anticancer efficacy. In addition, the challenges and prospects of how these insights can be translated into clinical benefits are discussed.

Accelerating amorphous polymer electrolyte screening by learning to reduce errors in molecular dynamics simulated properties.

Polymer electrolytes are promising candidates for the next generation lithium-ion battery technology. Large scale screening of polymer electrolytes is hindered by the significant cost of molecular dynamics (MD) simulation in amorphous systems: the amorphous structure of polymers requires multiple, repeated sampling to reduce noise and the slow relaxation requires long simulation time for convergence. Here, we accelerate the screening with a multi-task graph neural network that learns from a large amount of noisy, unconverged, short MD data and a small number of converged, long MD data. We achieve accurate predictions of 4 different converged properties and screen a space of 6247 polymers that is orders of magnitude larger than previous computational studies. Further, we extract several design principles for polymer electrolytes and provide an open dataset for the community. Our approach could be applicable to a broad class of material discovery problems that involve the simulation of complex, amorphous materials.

Study on the application of oral digital design in aesthetic restoration of anterior teeth of cleft lip/palate patients.

OBJECTIVES: A study was conducted to investigate the clinical effects of oral digital design on the aesthetic restoration of anterior teeth of cleft lip/palate patients. METHODS: Nine adult cleft lip/palate patients who need aesthetic restoration of anterior teeth were recruited. Digital information of patients' dental arches, the surrounding soft tissue and face were captured by digital camera and scanner. The aesthetic analysis and design were conducted using keynote and 3shape software and were demonstrated to the patients. The optimized treatment plan was ensured by communicating with the patients. Digital wax-up models were exported and printed into resin diagnostic models, which were then utilized in the treatment process to guide the doctors and the technicians in tooth preparation and in making the final restorations, respectively. The adhesive procedure was completed after satisfactory try-in. Aesthetics assessment was conducted in accordance with the anterior esthetic evaluation form. The scores of patient's satisfaction were recorded on a questionnaire containing six items of aesthetic index and doctor-patient communication. Patients were interviewed and examined after 1, 3, 6, and 12 months, respectively, and the clinical effects of restorations were evaluated. RESULTS: All nine patients had satisfactory clinical results. The aesthetic defects of the patients were effectively addressed. All treatments met the requirements of the preoperative digital designs. The patients' scores were all above 90 on the satisfaction scale. At 12 months after the operation, the clinical effects of restorations of all cases achieved A class in each evaluation indicator. CONCLUSIONS: For cleft lip/palate patients with esthetic defect in the anterior teeth, the digital design plays an important role in optimizing the treatment plan and guides the whole treatment process. This design can help clinicians achieve predictable satisfactory aesthetic results.

Measurement of three-dimensional changes in lip vermilion in adult female patients after orthodontic extraction: a retrospective longitudinal study.

BACKGROUND: 3D facial scanning has changed the way facial aesthetic is evaluated and has numerous advantages for facial analysis. The specific relationship between lip vermilion morphological changes after orthodontic extraction treatment has not been fully explained. The objective of this study was to evaluate 3D morphological changes after orthodontic extraction treatment in lip vermilion of adult females with dentoalveolar protrusion using a structured light-based scanner. METHODS: Forty-two female subjects (25.2 ± 1.9 years) were recruited as the treatment group; these patients had undergone extraction treatment and achieved better sagittal profiles. Twenty female subjects (25.5 ± 2.1 years) were enrolled in the non-treatment group; these patients did not require any orthodontic treatment. The follow up time for the treatment group was more than 24 months and for the non-treatment group was more than 12 months. 3D facial scans were captured using 3D CaMega. Six landmarks (Ls, Li, R.Chp, L.Chp, R.Ch, and L.Ch), three linear measurements (mouth height, philtrum width, and mouth width), and three area measurements (upper, lower, and total vermilion area) were measured. The spatial deviations of three volumetric measurements (upper, lower, and total vermilion) were constructed for quantitative analysis. Color-coded displacement map were constructed for visualization of the soft-tissue displacement as qualitative evaluation. RESULTS: Mouth height and philtrum width decreased (-0.93 mm and - 1.08 mm, respectively) significantly (p = 0.008 and p = 0.027, respectively), and no significant (p = 0.488) change in mouth width was observed in the treatment group. The lower and total vermilion surface areas decreased (-51.00mm2 and - 69.82mm2, respectively) significantly (p = 0.003 and p = 0.031, respectively) in the treatment group, but no statistically significant (p = 0.752) change was detected in the upper vermilion. In the treatment group, significant retractions were observed in the color-coded displacement map, and three volumetric measurements of vermilion changed significantly (p = 0.012, p = 0.001 and p = 0.004, respectively). Significant differences were found between the treatment group and the non-treatment group in the linear, area and volumetric measurements. CONCLUSIONS: This study established a method for qualitative and quantitative evaluation of the lip vermilion. Significant 3D retraction of the lip vermilion after the extraction treatment was found, with morphological variation between upper and lower vermilion.