Radiomics analysis for the prediction of locoregional recurrence of locally advanced oropharyngeal cancer and hypopharyngeal cancer.

PURPOSE: By radiomic analysis of the postcontrast CT images, this study aimed to predict locoregional recurrence (LR) of locally advanced oropharyngeal cancer (OPC) and hypopharyngeal cancer (HPC). METHODS: A total of 192 patients with stage III-IV OPC or HPC from two independent cohort were randomly split into a training cohort with 153 cases and a testing cohort with 39 cases. Only primary tumor mass was manually segmented. Radiomic features were extracted using PyRadiomics, and then the support vector machine was used to build the radiomic model with fivefold cross-validation process in the training data set. For each case, a radiomics score was generated to indicate the probability of LR. RESULTS: There were 94 patients with LR assigned in the progression group and 98 patients without LR assigned in the stable group. There was no significant difference of TNM staging, treatment strategies and common risk factors between these two groups. For the training data set, the radiomics model to predict LR showed 83.7% accuracy and 0.832 (95% CI 0.72, 0.87) area under the ROC curve (AUC). For the test data set, the accuracy and AUC slightly declined to 79.5% and 0.770 (95% CI 0.64, 0.80), respectively. The sensitivity/specificity of training and test data set for LR prediction were 77.6%/89.6%, and 66.7%/90.5%, respectively. CONCLUSIONS: The image-based radiomic approach could provide a reliable LR prediction model in locally advanced OPC and HPC. Early identification of those prone to post-treatment recurrence would be helpful for appropriate adjustments to treatment strategies and post-treatment surveillance.

Real-Time Observation for Dynamic Oscillation during Self-Assembly and Clearance of Aß42.

The dynamic oscillation implicated in structural heterogeneity during the self-assembly of amyloid peptide 1-42 (Aß42) may play a crucial role in eliciting cellular responses. We developed a real-time monitoring platform to observe an oscillatory non-equilibrium interaction that dominated the Aß42 clearance by neuronal cells during interplay with an oscillator (lipopolysaccharide, LPS). Molecular dynamics studies indicated that the electrostatic and hydrophobic segments of LPS involved in the temporary heteromolecular association and slightly decelerated the intrinsic thermally-induced protein dynamics of Aß42. A bait-specific intervention strategy could temporarily slow down the self-propagation of Aß42 to extend the lifetime of autonomous oscillation and augment Aß42 clearance of neuronal cells. The lifetime increment of oscillation shows a bait concentration-dependent manner to reflect the non-equilibrium binding strength. This relationship may serve as a predictor for Alzheimer's disease drug discovery.

Evolutionary dynamics under partner preferences.

The fact that people often have preference rankings for their partners is a distinctive aspect of human behavior. Little is known, however, about how this talent as a powerful force shapes human behavioral traits, including those which should not have been favored by selection, such as cooperation in social dilemma situations. Here we propose a dynamic model in which network-structured individuals can switch their interaction partners within neighborhoods based on their preferences. For the partner switching, we propose two interruption regimes: dictatorial regime and negotiating regime. In the dictatorial regime, focal individuals are able to suspend interactions out of preferences unilaterally. In the negotiating regime, either focal individuals or the associated partners agree to suspend, then these interactions can be successfully suspended. We investigate the evolution of cooperation under both preference-driven partner switching regimes in the context of both the weakened variant of the donation game and the standard one. Specifically, we theoretically approximate the critical conditions for cooperation to be favored by weak selection in the weakened donation game where cooperators bear a unit cost to provide a benefit for each active neighbor and simulate the evolutionary dynamics of cooperation in the standard donation game to test the robustness of the analytical results. Under dictatorial regime, selection of cooperation becomes harder when individuals have preferences for either cooperator or defector partners, implying that the expulsion of defectors by cooperators is overwhelmed by the chasing of defectors towards cooperators. Under negotiating regime, both preferences for cooperator and defector partners can significantly favor the evolution of cooperation, yet underlying mechanisms differ greatly. For preferences over cooperator partners, cooperator-cooperator interaction relationships are reinforced and the associated mutual reciprocity can resist and assimilate defectors. For preferences over defector partners, defector-defector interaction relationships are anchored, weakening defectors' exploitation over cooperators. Cooperators are thus offered much time space to interact among cospecies and spread. Our work may help better understand the critical role of preference-based adaptive partner switching in promoting the evolution of cooperation.

Prediction of poor outcome in stroke patients using radiomics analysis of intraparenchymal and intraventricular hemorrhage and clinical factors.

PURPOSE: To build three prognostic models using radiomics analysis of the hemorrhagic lesions, clinical variables, and their combination, to predict the outcome of stroke patients with spontaneous intracerebral hemorrhage (sICH). MATERIALS AND METHODS: Eighty-three sICH patients were included. Among them, 40 patients (48.2%) had poor prognosis with modified Rankin scale (mRS) of 5 and 6 at discharge, and the prognostic model was built to differentiate mRS ≤ 4 vs. 5 + 6. The region of interest (ROI) of intraparenchymal hemorrhage (IPH) and intraventricular hemorrhage (IVH) were separately segmented. Features were extracted using PyRadiomics, and the support vector machine was applied to select features and build radiomics models based on IPH and IPH + IVH. The clinical models were built using multivariate logistic regression, and then the radiomics scores were combined with clinical variables to build the combined model. RESULTS: When using IPH, the AUC for radiomics, clinical, and combined model was 0.78, 0.82, and 0.87, respectively. When using IPH + IVH, the AUC was increased to 0.80, 0.84, and 0.90, respectively. The combined model had a significantly improved AUC compared to the radiomics by DeLong test. A clinical prognostic model based on the ICH score of 0-1 only achieved AUC of 0.71. CONCLUSIONS: The combined model using the radiomics score derived from IPH + IVH and the clinical factors could achieve a high accuracy in prediction of sICH patients with poor outcome, which may be used to assist in making the decision about the optimal care.

Bronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro.

Although epithelial-mesenchymal transition (EMT) is a common feature of fibrotic lung disease, its role in fibrogenesis is controversial. Recently, aberrant basaloid cells were identified in fibrotic lung tissue as a novel epithelial cell type displaying a partial EMT phenotype. The developmental origin of these cells remains unknown. To elucidate the role of EMT in the development of aberrant basaloid cells from the bronchial epithelium, we mapped EMT-induced transcriptional changes at the population and single-cell levels. Human bronchial epithelial cells grown as submerged or air-liquid interface (ALI) cultures with or without EMT induction were analyzed by bulk and single-cell RNA-Sequencing. Comparison of submerged and ALI cultures revealed differential expression of 8,247 protein coding (PC) and 1,621 long noncoding RNA (lncRNA) genes and revealed epithelial cell-type-specific lncRNAs. Similarly, EMT induction in ALI cultures resulted in robust transcriptional reprogramming of 6,020 PC and 907 lncRNA genes. Although there was no evidence for fibroblast/myofibroblast conversion following EMT induction, cells displayed a partial EMT gene signature and an aberrant basaloid-like cell phenotype. The substantial transcriptional differences between submerged and ALI cultures highlight that care must be taken when interpreting data from submerged cultures. This work supports that lung epithelial EMT does not generate fibroblasts/myofibroblasts and confirms ALI cultures provide a physiologically relevant system to study aberrant basaloid-like cells and mechanisms of EMT. We provide a catalog of PC and lncRNA genes and an interactive browser (https://bronc-epi-in-vitro.cells.ucsc.edu/) of single-cell RNA-Seq data for further exploration of potential roles in the lung epithelium in health and lung disease.

Transdermal Delivery of Succinate Accelerates Energy Dissipation of Brown Adipocytes to Reduce Remote Fat Accumulation.

Weight loss by increasing energy consumption of thermogenic adipocytes to overcome obesity remains a challenge. Herein, we established a transdermal device that was based on the local and temporarily controlled delivery of succinate (SC), a tricarboxylic acid cycle metabolic intermediate to stimulate the thermogenesis pathway of uncoupling protein 1 (UCP1) and accelerate energy dissipation of brown adipose tissue (BAT) under the dorsal interscapular skin, further initiating the consumption of fatty acids by systemic metabolism. SC microneedle patches significantly suppressed weight gain and fat accumulation of remote organs, including liver and peripheral white adipose tissue (WAT) in high-fat diet-induced obese mice. mRNA expression levels of Ucp1 in BAT and other browning markers in WAT were significantly elevated in the mice that were treated with SC microneedle. Thus, the energy dissipation of BAT using UCP1-mediated thermogenesis accelerated by the transdermal delivery of SC may become a potential and effective strategy for preventing obesity.

Evolutionary dynamics of zero-determinant strategies in repeated multiplayer games.

Several studies have confirmed the existence of zero-determinant (ZD) strategies in repeated social dilemmas since Press and Dyson's ingenious discovery of ZD strategies in iterated prisoner's dilemmas. However, less research studies evolutionary performance of multiplayer ZD strategies, especially from a theoretical perspective. Here, we use a state-clustering method to theoretically analyze evolutionary dynamics of two representative ZD strategies: generous ZD strategies and extortionate ZD strategies. We consider two new settings for multiplayer ZD strategies: competitions with all ZD strategies and competitions with all memory-one strategies, apart from the competitions between these strategies and some classical ones. Moreover, we investigate the influence of the level of generosity and extortion on evolutionary dynamics of generous and extortionate ZD strategies, which was commonly ignored in previous studies. Theoretical results show that players with limited generosity are at an advantageous place and extortioners extorting more severely hold their ground more readily. Our results may provide new insights into better understanding evolutionary dynamics of ZD strategies in repeated multiplayer games.

Solid tumor size for prediction of recurrence in large and giant non-functioning pituitary adenomas.

A subset of large non-functioning pituitary adenomas (lNFPA) and giant non-functioning pituitary adenomas (gNFPA) undergoes early progression/recurrence (P/R) after surgery. This study revealed the clinical and image predictors of P/R in lNFPA and gNFPA, with emphasis on solid tumor size. This retrospective study investigated the preoperative MR imaging features for the prediction of P/R in lNFPA (> 3 cm) and gNFPA (> 4 cm). Only the patients with a complete preoperative brain MRI and undergone postoperative MRI follow-ups for more than 1 year were included. From November 2010 to December 2020, a total of 34 patients diagnosed with lNFPA and gNFPA were included (median follow-up time 47.6 months) in this study. A total of twenty-three (23/34, 67.6%) patients had P/R, and the median time to P/R is 25.2 months. Solid tumor diameter (STD), solid tumor volume (STV), and extent of resection are associated with P/R (p < 0.05). Multivariate analysis showed large STV is a risk factor for P/R (p < 0.05) with a hazard ratio of 30.79. The cutoff points of STD and STV for prediction of P/R are 26 mm and 7.6 cm3, with AUCs of 0.78 and 0.79 respectively. Kaplan-Meier analysis of tumor P/R trends showed that patients with larger STD and STV exhibited shorter progression-free survival (p < 0.05). For lNFPA and gNFPA, preoperative STD and STV are significant predictors of P/R. The results offer objective and valuable information for treatment planning in this subgroup.

Factors Associated with patient satisfaction towards a prison detention Clinic Care among male drug-using inmates.

This study assessed patient satisfaction and its associated factors among male drug-using inmates utilizing a prison detention clinic in Taiwan. A cross-sectional design and structured questionnaire were employed to recruit 580 drug-using inmates into the study. The Patient Satisfaction Questionnaire Short Form (PSQ-18), developed by the RAND Corporation, was used as the basis for the short scale of patient satisfaction, and the research data were analyzed using the SPSS for Windows 20.0 statistical software package. The results showed that the research subjects had low patient satisfaction in all the factors assessed compared with the scale's general norms. Among the original seven satisfaction subscales in this study, the highest score was for the financial aspects, and the lowest was for the amount of time spent with doctors. This study also investigated satisfaction with medical lab exams and the pharmacy at the prison's clinic, and the satisfaction scores were higher than the original seven subscales. In multiple logistic regression analyses, the final model indicated that the inmates undergoing observed rehabilitation (OR = 13.837, 95% CI = 2.736-69.983) were more likely satisfied with prison detention clinic c than those serving prison sentences. Those inmates with custodial deposits (high vs. low; OR = 1.813, 95% CI = 1.038-3.168), and meet their physical health needs (met vs. unmet; OR = 4.872, 95% CI = 2.054-11.560) had significant correlated with detention clinic care satisfactory level. Although there is only one study setting cannot give a generalizability for people who are incarcerated in Taiwan, this study highlights that the prison authorities should scrutinize factors associated with detention clinic care satisfaction, such as the type of inmate, economic status in the prison, self-reported health status, and their physical health needs, to increase the level of patient satisfaction.

One-Year Treatment Outcome of Profile Changes After Transcutaneous Maxillary Distraction Osteogenesis in Growing Children With Cleft Lip and Palate.

OBJECTIVE: To evaluate the long-term stability of LeFort I osteotomy followed by distraction osteogenesis with a transcutaneous rigid external device for the treatment of severe maxillary hypoplasia in patients with cleft lip and palate. PATIENTS AND METHODS: Nine patients with cleft lip and palate underwent rigid external distraction after a LeFort I osteotomy for maxillary advancement. Lateral cephalometric films were analyzed for assessment of treatment outcome and stability in 1 month, 6 months, and 1 year after distraction. RESULTS: Significant maxillary advancement was observed in the horizontal direction, with the anterior nasal spine (ANS) distance of the maxilla increasing by an average of 20.5 ± 5.1 mm after distraction. The ANS relapse rates in 6 months and 1 year were 8.7% and 12.8%, respectively. The mean inclination of upper incisors to the palatal plane was almost unchanged (before: 109.8° ± 6.6°; after: 108.9° ± 7.5°). The movement ratios at the nasal tip/ANS, soft tissue A point/A point, and the upper vermilion border/upper incisor edge were 0.36:1, 0.72:1, and 0.83:1, respectively. CONCLUSION: Considerable maxillary advancement was achieved with less change of incisors inclination after distraction. Moreover, the relapse rate after 1 year was minimal. The concave facial profile was improved as well as the facial balance and aesthetics.

Longitudinal alterations of the cisternal segment of trigeminal nerve and brain pain-matrix regions in patients with trigeminal neuralgia before and after treatment.

BACKGROUND: Trigeminal neuralgia (TN) is the most common type of chronic neuropathic facial pain, but the etiology and pathophysiological mechanisms after treatment are still not well understood. The purpose of this study was to investigate the longitudinal changes of the cisternal segment of the trigeminal nerve and brain pain-related regions in patients with TN before and after treatment using readout segmentation of long variable echo-train (RESOLVE) diffusion tensor imaging (DTI) and transverse relaxation (T2)-weighted sampling perfection with application-optimized contrast at different flip angle evolutions (T2-SPACE). METHODS: Twelve patients with TN and four healthy controls were enrolled in this study. All patients underwent assessment of the visual analog scale (VAS), and acquisition of RESOLVE DTI and T2-SPACE images before and at 1, 6, and 12 months after treatments. Regions-of-interest were placed on the bilateral anterior, middle, and posterior parts of the cisternal segment of the trigeminal nerve, the bilateral root entry zone (REZ), bilateral nuclear zone, and the center of pontocerebellar tracts, respectively. Voxel-based morphometry (VBM) analysis was conducted with T2-SPACE images, and gray matter volumes (GMV) were measured from brain pain-matrix regions. RESULTS: The results demonstrated that the VAS scores, the axial diffusivity of the middle part of the affected cisternal trigeminal nerve, the fractional anisotropy of the bilateral nuclear zones, and the mean diffusivity of the center of pontocerebellar tract significantly changed over time before and after treatment. The changes of GMV in the pain-matrix regions exhibited similar trends to the VAS before and after treatment. CONCLUSION: We conclude that magnetic resonance imaging with RESOLVE DTI and VBM with T2-SPACE images were helpful in the understanding of the pathophysiological mechanisms in patients with TN before and after treatment.

Reduction of aldehyde emission and attribution of environment burden in cooking fumes from food stalls using a novel fume collector.

Uncontrolled cooking emissions from commercial kitchens are problematic due to their corresponding health effects and malodors. To reduce cooking emissions, medium and large commercial kitchens install air pollution control devices, such as electrostatic precipitators and wet scrubbers, while small-scale commercial cooking workplaces, such as street-food stalls, use smaller, simpler, and less costly filtration and absorption devices. However, these smaller devices may be poorly designed and recirculate cooking emissions in the workplace. The objectives of this study were to design and implement a novel fume collector and evaluate its effectiveness in reducing aldehydes and the corresponding environmental burden emitted by food stalls. Two stalls, which had malodor problems despite the use of fume collectors, volunteered to participate in the study. To increase the efficiency of the existing fume collectors, a new collector was designed comprising two buckets connected in series, each with pollutant absorption (NaClO-surfactant mixed solution) and particulate filtration (activated-carbon filters) components. Total aldehyde concentrations measured at the exhaust outlets of the original and new collectors were 342.2 and 80.8 µg/m3 for stall A, and 622.7 and 283.1 µg/m3 for stall B, respectively. The corresponding concentration reductions for stall A and B were 76% and 55%, and the emission rate reductions were 91% (from 749 to 71 g/yr) and 76% (from 1040 g/yr to 248 g/h), respectively. These results demonstrate that the effectiveness of the novel collector at removing cooking fumes was significantly improved. The high efficiency and low-cost nature of the collector make it highly applicable in small-scale commercial kitchens and street-food stalls.

Prediction of mTICI 3 recanalization and clinical outcomes in endovascular thrombectomy for acute ischemic stroke: a retrospective study in the Taiwan registry.

PURPOSE: Early recanalization for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) by endovascular thrombectomy (EVT) is strongly related to improved functional outcomes. With data obtained from the Taiwan registry, the factors associated with mTICI 3 recanalization and clinical outcomes in EVT are investigated. METHODS: From January 2014 to September 2016, 108 patients who underwent EVT for AIS due to LVO in 11 medical centers throughout Taiwan were included. Complete recanalization is defined as achieving modified thrombolysis in cerebral infarction (mTICI) grade 3. Good clinical outcomes are defined by the modified Rankin scale (mRS) 0-2 at 3 months after EVT. Clinical and imaging parameters for predicting mTICI 3 recanalization and good clinical outcomes are analyzed. RESULTS: Of the 108 patients who received EVT, 54 (50%) patients had mTICI 3 recanalization. Having received aspiration only and the use of IV-tPA are shown to be significant predictors for mTICI 3 recanalization with odds ratios of 2.61 and 2.53 respectively. Forty-six (42.6%) patients experienced good 3-month clinical outcomes (mRS 0-2). Pretreatment collateral statuses, NIHSS scores, time lapses between symptoms to needle, and the occurrence of hemorrhage at 24 h are all significant predictors for good outcomes with odds ratios of 2.88, 0.91, 0.99, and 0.31 respectively. CONCLUSIONS: Prediction of mTICI 3 recanalization and clinical outcomes offer valuable clinical information for treatment planning in EVT.

Roles of autophagy in orthodontic tooth movement.

INTRODUCTION: Orthodontic tooth movement (OTM) relies on efficient remodeling of alveolar bone. While a well-controlled inflammatory response is essential during OTM, the mechanism regulating inflammation is unknown. Autophagy, a conserved catabolic pathway, has been shown to protect cells from excess inflammation in disease states. We hypothesize that autophagy plays a role in regulating inflammation during OTM. METHODS: A split-mouth design was used to force load molars in adult male mice, carrying a GFP-LC3 transgene for in vivo detection of autophagy. Confocal microscopy, Western blot, and quantitative polymerase chain reaction analyses were used to evaluate autophagy activation in tissues of loaded and control molars at time points after force application. Rapamycin, a Food and Drug Administration-approved immunosuppressant, was injected to evaluate induction of autophagy. RESULTS: Autophagy activity increases shortly after loading, primarily on the compression side of the tooth, and is closely associated with inflammatory cytokine expression and osteoclast recruitment. Daily administration of rapamycin, an autophagy activator, led to reduced tooth movement and osteoclast recruitment, suggesting that autophagy downregulates the inflammatory response and bone turnover during OTM. CONCLUSIONS: This is the first demonstration that shows that autophagy is induced by orthodontic loading and plays a role during OTM, likely via negative regulation of inflammatory response and bone turnover. Exploring roles of autophagy in OTM holds great promise, as aberrant autophagy is associated with periodontal disease and its related systemic inflammatory disorders.

Supramolecular Bait to Trigger Non-Equilibrium Co-Assembly and Clearance of Aß42.

In living systems, non-equilibrium states that control the assembly-disassembly of cellular components underlie the gradual complexification of life, whereas in nonliving systems, most molecules follow the laws of thermodynamic equilibrium to sustain dynamic consistency. Little is known about the roles of non-equilibrium states of interactions between supramolecules in living systems. Here, a non-equilibrium state of interaction between supramolecular lipopolysaccharide (LPS) and Aß42, an aggregate-prone protein that causes Alzheimer's disease (AD), was identified. Structurally, Aß42 presents a specific groove that is recognized by the amphiphilicity of LPS bait in a non-equilibrium manner. Functionally, the transient complex elicits a cellular response to clear extracellular Aß42 deposits in neuronal cells. Since the impaired clearance of toxic Aß42 deposits correlates with AD pathology, the non-equilibrium LPS and Aß42 could represent a useful target for developing AD therapeutics.

Correlation of internal carotid artery diameter and carotid flow with asymmetry of the circle of Willis.

BACKGROUND: The purpose of this study was to clarify the effect of asymmetric COW variants on carotid flow changes, and proposed an easy estimate of the representative carotid flow volume for accurate numerical simulation. METHODS: A total of 210 healthy adults receiving magnetic resonance angiography and carotid duplex sonography were included. Three anterior cerebral artery asymmetry (AA) groups were defined based on the diameter ratio difference (DRD) of bilateral A1 segments: AA1 group, one-side A1 aplasia; AA2, A1 DRD ≥ 50%; AA3, A1 DRD between 10 and 50%. Similarly, 3 posterior communicating artery (PcomA) asymmetry (PA) groups were defined: PA1 group, one fetal-origin posterior cerebral artery and absent contralateral PcomA; PA2, PcomA DRD ≥ 50%; PA3, PcomA DRD between 10 and 50%. RESULTS: With A1 asymmetry, the ICA diameter of the dominant A1 is significantly greater than the contralateral side. Significant differences of bilateral ICA flow were present in the AA1 and AA2 groups (mean flow difference 42.9 and 30.7%, respectively). Significant bilateral ICA diameter and flow differences were only found in the PA1 group. Linear regression analysis of ICA diameter and flow found a moderately positive correlation between ICA diameter and flow in all AA groups, with a 1 mm increment in vessel diameter corresponding to a 62.6 ml increment of flow volume. The product of bilateral ICA diameter and flow volume difference (ICA-PDF) could be a potential discriminator with a cutoff of 4.31 to predict A1 asymmetry ≥50% with a sensitivity of 0.81 and specificity of 0.76. CONCLUSIONS: The study verifies that A1 asymmetry causes unequal bilateral carotid inflow, and consequently different bilateral ICA diameters. Adjustment of the inflow boundary conditions according to the COW variants would be necessary to improve the accuracy of numerical simulation.

Accuracy assessment of computer-aided three-dimensional simulation and navigation in orthognathic surgery (CASNOS).

PURPOSE: This study is aimed for measuring the accuracy of simulation and prediction of our CASNOS protocol in adult patients treated with 2-jaw orthognathic surgery. METHODS: Adult patients with skeletal Class III malocclusions requiring 2-jaw orthognathic surgery were enrolled in the study. Three-dimensional imaging data of 1-month pre-surgical (T1) and 6-month post-surgical (T2) CT were compared to assess accuracy of CASNOS planning. The accuracy of CASNOS protocol was evaluated by calculating the differences in the positions of selected landmarks between simulated surgical and post-surgical 3D images parameters, including ANB, A-Nv, Pog-Nv, and the positions of selected landmarks (ANS, Point A, Point B, Pog) changes in horizontal (x-axis) and vertical (y-axis) directions. Overall geographical discrepancy of planning was assessed by superimposing the color mapping of T1 and T2 imaging. RESULTS: Thirty adult patients with a mean age of 20.6 ± 1.5 years (female/male = 18/12) were enrolled. The geographical changes of overall superimposition between the planned and post-surgical imaging was 0.60 ± 0.19 mm (range: 0.42-1.08 mm). The discrepancies between simulated and post-surgical ANB, A-Nv, Pog-Nv were 1.16 ± 0.36°, 1.25 ± 0.33 mm, 1.19 ± 0.35 mm, respectively. The deviations between simulated and post-surgical Point A and Point B positions were within 1 mm in horizontal and vertical directions. CONCLUSION: The application of the pre-designed bony guiding splints of CASNOS protocol can allow surgeons to treat patients with craniofacial deformities precisely. CASNOS provides a novel approach for orthodontists and surgeons accurately remedying the patients with complex craniofacial discrepancies.

The Bioactive Core and Corona Synergism of Quantized Gold Enables Slowed Inflammation and Increased Tissue Regeneration in Wound Hypoxia.

The progress of wound regeneration relies on inflammation management, while neovascular angiogenesis is a critical aspect of wound healing. In this study, the bioactive core and corona synergism of quantized gold (QG) were developed to simultaneously address these complicated issues, combining the abilities to eliminate endotoxins and provide oxygen. The QG was constructed from ultrasmall nanogold and a loosely packed amine-based corona via a simple process, but it could nonetheless eliminate endotoxins (a vital factor in inflammation also called lipopolysaccharides) and provide oxygen in situ for the remodeling of wound sites. Even while capturing endotoxins through electrostatic interactions, the catalytic active sites inside the nanogold could maintain its surface accessibility to automatically transform the overexpressed hydrogen peroxide in hypoxic wound regions into oxygen. Since the inflammatory stage is an essential stage of wound healing, the provision of endotoxin clearance by the outer organic corona of the QG could slow inflammation in a way that subsequently promoted two other important stages of wound bed healing, namely proliferation and remodeling. Relatedly, the efficacy of two forms of the QG, a liquid form and a dressing form, was demonstrated at wound sites in this study, with both forms promoting the development of granulation, including angiogenesis and collagen deposition. Thus, the simply fabricated dual function nanocomposite presented herein not only offers reduced batch-to-batch variation but also increased options for homecare treatments.

A Supramolecular Trap to Increase the Antibacterial Activity of Colistin.

A strong interaction between colistin, a last-resort antibiotic of the polymyxin family, and free lipopolysaccharide (LPS, also referred to as endotoxin), released from the Gram-negative bacterial (GNB) outer membrane (OM), has been identified that can decrease the antibacterial efficacy of colistin, potentially increasing the dose of this antibiotic required for treatment. The competition between LPS in the GNB OM and free LPS for the interaction with colistin was prevented by using a supramolecular trap to capture free LPS. The supramolecular trap, fabricated from a subnanometer gold nanosheet with methyl motifs (SAuM), blocks lipid A, preventing the interaction between lipid A and colistin. This can minimize endotoxemia and maximize the antibacterial efficacy of colistin, enabling colistin to be used at lower doses. Thus, the potential crisis of colistin resistance could be avoided.

Phenotype affinity mediated interactions can facilitate the evolution of cooperation.

We study the coevolutionary dynamics of the diversity of phenotype and the evolution of cooperation in the Prisoner's Dilemma. Rather than pre-assigning zero-or-one interaction rate, we diversify the rate of interaction by associating it with phenotypes. Individuals each carry a set of potentially expressible traits and expresses a number of such traits at a cost proportional to the number. The set of traits expressed constitutes phenotype. Phenotypes and thus the rate of interaction are evolvable over time. Our results show that nonnegligible cost of expressing traits restrains phenotype diversity, and the evolutionary race mainly proceeds on between cooperative strains and defective strains who express a very few traits. It pays for cooperative strains to express a very few traits. Though such a low level of expression weakens reciprocity between cooperative strains, it decelerates the rate of interaction between cooperative strains and defective strains to a larger degree, leading to the predominance of cooperative strains over defective strains. We also find that evolved diversity of phenotype can occasionally destabilize due to the invasion of defective mutants, implying that cooperation and diversity of phenotype can mutually reinforce each other. Our results may help better understand the coevolution of cooperation and the diversity of phenotype.