Rapid, portable and visualizing nitrite detection enabled by a rationally designed meso-aminoindole substituted pyronine-based fluorescent probe.

Nitrite (NO2-) widely exists in our daily diet, and its excessive consumption can lead to detrimental effects on the human central nervous system and an elevated risk of cancer. The fluorescence probe method for the determination of nitrite has developed rapidly due to its simplicity, rapidity and sensitivity. Despite establishing various nitrite sensing platforms to ensure the safety of foods and drinking water, the simultaneous achievement of rapid, specific, affordable, visualizing, and on-site nitrite detection remains challenging. Here, we designed a novel fluorescent probe by using Rhodamine 800 as the fluorescent skeleton and 5-aminoindole as the specific reaction group to solve this problem. The probe shows a maximal fluorescence emission at 602 nm, thereby avoiding background emission interference when applied to food samples. Moreover, this unique probe exhibited excellent sensing capabilities for detecting nitrite. These included: a rapid response time within 3 min, a noticeable color change that the naked eye can observe, a low detection limit of 13.8 nM, and a remarkable selectivity and specificity to nitrite. Besides that, the probe can detect nitrite quantitatively in barreled drinking water, ham sausage, and pickles samples, with good recoveries ranging from 89.0 % to 105.8 %. More importantly, based on the probe fixation and signal processing technology, a portable and smart sensing platform was fabricated and made convenient and rapid analysis the content of NO2- in real samples possible. The results obtained in this work provide a new strategy for the design of high-performance nitrite probes and feasible technology for portable, rapid and visual detection of nitrite, and this probe holds the potential as a practical tool for alleviating concern regarding nitrite levels.

Chlorin e6 and BLZ945 Based Self-Assembly for Photodynamic Immunotherapy Through Immunogenic Tumor Induction and Tumor-Associated Macrophage Depletion.

Immunotherapeutic effect is restricted by the nonimmunogenic tumor phenotype and immunosuppression behaviors of tumor-associated macrophages (TAMs). In this work, a drug self-assembly (designated as CeBLZ) is fabricated based on chlorin e6 (Ce6) and BLZ945 to activate photodynamic immunotherapy through tumor immunogenic induction and tumor-associated macrophage depletion. It is found that Ce6 tends to assemble with BLZ945 without any drug excipients, which can enhance the cellular uptake, tumor penetration, and blood circulation behaviors. The robust photodynamic therapy effect of CeBLZ efficiently suppresses the primary tumor growth and also triggers immunogenic cell death to reverse the nonimmunogenic tumor phenotype. Moreover, CeBLZ can deplete TAMs in tumor tissues to reverse the immunosuppression microenvironment, activating abscopal effect for distant tumor inhibition. In vitro and in vivo results confirm the superior antitumor effect of CeBLZ with negligible side effect, which might promote the development of sophisticated drug combinations for systematic tumor management.

Normscan: open-source Python software to create average models from CT scans.

PURPOSE: Age-matched average 3D models facilitate both surgical planning and intraoperative guidance of cranial birth defects such as craniosynostosis. We aimed to develop an algorithm that accepts any number of CT scans as input and generates highly accurate, average models with minimal user input that are ready for 3D printing and clinical use. METHODS: Using a compiled database of 'normal' pediatric computed tomography (CT) scans, we report Normscan, an open-source platform built in Python that allows users to generate normative models of CT scans through user-defined landmarks. We use the basion, nasion, and left and right porions as anatomical landmarks for initial correspondence and then register the models using the iterative closest points algorithm before downstream averaging. RESULTS: Normscan is fast and easy to use via our user interface and also creates highly accurate average models of any number of input models. Additionally, it is highly repeatable, with coefficients of variance for the surface area and volume of the average model being less than 3% across ten independent trials. Average models can then be 3D printed and/or visualized in augmented reality. CONCLUSIONS: Normscan provides an end-to-end pipeline for the creation of average models of skulls. These models can be used for the generation of databases of specific demographic anatomical models as well as for intraoperative guidance and surgical planning. While Normscan was designed for craniosynostosis repair, due to the modular nature of the algorithm, Normscan has many applications in other areas of surgical planning and research.

Alterations in Sphenoid Anatomy in Craniosynostosis: Implications for Fronto-Orbital Advancement.

OBJECTIVE: Fronto-orbital advancement involves removal of the fronto-orbital bandeau. Visualization of the saw blade is lost as it passes through the fronto-orbital-sphenoid junction (FOSJ), placing the temporal lobe at risk of injury. We aim to provide a 3D analysis of the space surrounding this osteotomy to differentiate various types of craniosynostoses. DESIGN: Retrospective cohort. SETTING: Institutional. PATIENTS: Thirty patients with isolated unicoronal synostosis, nonsyndromic bicoronal synostosis, metopic synostosis, Apert syndrome, Crouzon syndrome, and Muenke syndrome. INTERVENTIONS: CT scans conducted between 2 months to 2 years of age were 3D reconstructed to compare craniometrics against normal controls. MAIN OUTCOME MEASURE(S): Craniometrics. RESULTS: The mean bone thickness of the FOSJ at the level of the supraorbital rim was significantly small for the Apert, unicoronal and bicoronal groups. The mean vertical height of the middle cranial fossa from the lesser sphenoid wing was significantly greater in the unicoronal group. The mean vertical height of the tip of the temporal lobe from the lateral sphenoid ridge was greater in the unicoronal, isolated bicoronal, and Apert groups. The mean corneal protrusion beyond the lateral orbital rim was significantly greater in the Apert and unicoronal groups. The mean horizontal depth of the orbit was smallest in the Apert group. The mean vertical distance between the dacryon and the foramen cecum, and the mean volume of temporal lobe beneath the sphenoid shelf were the largest in the Apert group. CONCLUSIONS: Patients with Apert syndrome have the most unfavorable morphology of the anterior and middle cranial fossae.

Rapid quantitative evaluation of total polar materials (TPM) in frying oil based on an "off-on" fluorescence viscosity response probe.

The content of total polar material (TPM) is considered as a comprehensive indicator to evaluate the quality of edible oils which should be discarded and no longer be used when TPM content exceeding 27 %. Nevertheless, there is currently a lack of a convenient and efficient TPM detection method, which is a meaningful challenge. With the increase of TPM content, the viscosity of frying oil grows, and the two maintain a satisfactory positive correlation. Consequently, an "off-on" fluorescence probe TCF-PR method based on viscosity-response has been developed. There exists a good linear relationship between the fluorescence intensity of the probe and the TPM content of soybean oil ((R2 = 0.9936) and salad oil (R2 = 0.9878), accompanying with the advantage of fast response (3 s), which means the rapid detection of TPM can be realized to determine the quality of frying oil in the field of food safety.

Tackling the water solubility dilemma of spiroring-closing rhodamine: Sulfone-functionalization enabling rational designing water-soluble probe for rapid visualizing mercury ions in cosmetics.

Rhodamine derivatives possessing spiroring-closing structures exhibit colorlessness, while the induction of spiroring-opening by metal ions results in notable color changes, rendering them as ideal platform for the development of functional probes with broad applications. However, the spiroring-closing form of rhodamine-based probes exhibits limited water solubility due to its neutral character, necessitating the incorporation of organic solvents to enhance solubility, which may adversely affect the natural system. Designing rhodamine probes with high solubility in both the zwitterionic and neutral form is of utmost importance and presents a significant challenge. This study presents a sulfone-rhodamine-based probe that exhibits good water solubility both in the spiroring opening and closing for detecting Hg2+. Upon the presence of Hg2+, the color undergoes a noticeable change from colorless to pink, with a response time of less than 1 min. probe 1 demonstrates an excellent linear relationship with Hg2+ concentrations within the range of 0-8 µM, and achieves a detection limit is 17.26 nM. The effectiveness of probe 1 was confirmed through the analysis of mercury ions in cosmetic products. Utilizing this probe, test paper strips have been developed to enhance the portability of Hg2+ detection naked eyes.

Chemotherapy-Enabled Colorectal Cancer Immunotherapy of Self-Delivery Nano-PROTACs by Inhibiting Tumor Glycolysis and Avoiding Adaptive Immune Resistance.

The chemo-regulation abilities of chemotherapeutic medications are appealing to address the low immunogenicity, immunosuppressive lactate microenvironment, and adaptive immune resistance of colorectal cancer. In this work, the proteolysis targeting chimera (PROTAC) of BRD4 (dBET57) is found to downregulate colorectal cancer glycolysis through the transcription inhibition of c-Myc, which also inhibits the expression of programmed death ligand 1 (PD-L1) to reverse immune evasion and avoid adaptive immune resistance. Based on this, self-delivery nano-PROTACs (designated as DdLD NPs) are further fabricated by the self-assembly of doxorubicin (DOX) and dBET57 with the assistance of DSPE-PEG2000. DdLD NPs can improve the stability, intracellular delivery, and tumor targeting accumulation of DOX and dBET57. Meanwhile, the chemotherapeutic effect of DdLD NPs can efficiently destroy colorectal cancer cells to trigger a robust immunogenic cell death (ICD). More importantly, the chemo-regulation effects of DdLD NPs can inhibit colorectal cancer glycolysis to reduce the lactate production, and downregulate the PD-L1 expression through BRD4 degradation. Taking advantages of the chemotherapy and chemo-regulation ability, DdLD NPs systemically activated the antitumor immunity to suppress the primary and metastatic colorectal cancer progression without inducing any systemic side effects. Such self-delivery nano-PROTACs may provide a new insight for chemotherapy-enabled tumor immunotherapy.

A novel amidine-based fluorescent probe TPE-4+ for rapid detection of anionic surfactant sodium dodecyl sulfate.

An accurate, fast, and simple surfactant detection method is of great significance for monitoring surfactants pollution. Sodium dodecyl sulfate (SDS) is one of the most commonly used anionic surfactants and has been listed as an important monitoring pollutant for surfactant residues. Herein, a novel fluorescent probe named TPE-4+ with four amidines as the recognition functional group and tetraphenylethene as the fluorophore was fabricated. Due to the special intramolecular environment, the probe showed selectively identification towards SDS which made an aggregation induced fluorescence enhencement. Under the optimum conditions, the fluorescence enhencement of TPE-4+ is linearly related to the concentration of SDS in the range of 5.0-60.0 µM with limit of detection (LOD) of 0.010 µM and limit of quantification (LOQ) of 0.034 µM. Relative to the reported methods, the probe in our work showed better selectivity and sensitivity. The proposed method was successfully applied for the SDS determination of disinfecting bowls.

Incidence of Sinusitis Postoperatively in Orthognathic Surgery: A Systematic Review and Meta-Analysis.

Maxillary osteotomies as a component of orthognathic surgery disrupt the normal anatomy and function of the sinus. The osteotomy with advancement of the inferior component of the sinus leaves a bony and mucosal opening in the sinus. Immediately after surgery, nasal drainage is impeded because of intranasal swelling. Acute and chronic maxillary sinusitis would be expected; however, its incidence as an expected complication is not well documented. A systematic review and meta-analysis was completed using PubMed to determine the incidence of sinusitis after maxillary orthognathic surgery. Studies were reviewed by two authors, and incidence data were extracted. Two hundred six articles were identified with 24 meeting the criteria for analysis. The incidence of sinusitis was based on 4213 participants who had undergone orthognathic surgery. Twenty-three studies reported a total number of sinusitis cases, and the results demonstrated a pooled incidence of 3.3% (95% confidence interval: 1.77, 6.06). One study did not report a total number of cases but reported chronic sinusitis survey-duration-based and Lund-Mackay scores. These scores, respectively, worsened from 7.6 to 14.8 and from 1.58 to 2.90 postoperatively. Despite the variability of maxillary surgery, the surgical technique, and the postoperative management, the incidence is low but sinusitis does occur. Prospective studies with validated questionnaires within the context of a specific protocol may further elucidate the causality of sinusitis. Further, patients with sinonasal symptoms postsurgery should be encouraged to consult with an otolaryngologist to ensure prompt treatment.

Chimeric Peptide Engineered Nanomedicine for Synergistic Suppression of Tumor Growth and Therapy-Induced Hyperlipidemia by mTOR and PCSK9 Inhibition.

Chemotherapy-induced side effects restrain anti-tumor efficiency, with hyperlipidemia being the most common accompanying disease to cause treatment failure. In this work, a chimeric peptide-engineered nanomedicine (designated as PRS) was fabricated for the synergistic suppression of tumor growth and therapy-induced hyperlipidemia. Within this nanomedicine, the tumor matrix-targeting peptide palmitic-K(palmitic)CREKA can self-assemble into a nano-micelle to encapsulate Rapamycin (mTOR inhibitor) and SBC-115076 (PCSK9 inhibitor). This PRS nanomedicine exhibits a uniform nano-distribution with good stability which enhances intracellular drug delivery and tumor-targeting delivery. Also, PRS was found to synergistically inhibit tumor cell proliferation by interrupting the mTOR pathway and reducing Rapamycin-induced hyperlipidemia by increasing the production of LDLR. In vitro and in vivo results demonstrate the superiority of PRS for systematic suppression of tumor growth and the reduction of hyperlipidemia without initiating any other toxic side effects. This work proposes a sophisticated strategy to inhibit tumor growth and also provides new insights for cooperative management of chemotherapy-induced side effects.

Virtual Reality Planning in Reconstructive Surgery for Orbital Prosthetic Rehabilitation Using ImmersiveTouch Platform: Preliminary Report.

BACKGROUND/PURPOSE: Virtual reality (VR) is emerging as an effective and intuitive surgical planning and 3D visualization tool. Digital surgical planning is the gold standard for planning the placement of implants in maxillofacial prosthetics, but the field lacks a platform exclusively designed to perform the task. Virtual reality planning (VRP) specific for maxillofacial prosthetics offers the clinician improved control of the presurgical planning and the potential to limit the need to adapt other advanced segmentation software. Furthermore, the virtual plan can be directly translated to the patient through custom 3D printed (3DP) surgical guides and visual aids. To the best of our knowledge, this article outlines the development of the world's first virtual reality planning platform and workflow for pre-operatory planning within a VR environment for clinical use specific to facial prosthetics and anaplastology. METHOD: The workflow was applied to managing 2 patients presenting with unilateral total exenteration and severe contracture enucleation, respectively (n=2). A cone-beam CT was acquired for each patient, and their data set was directly imported into the ImmersiveView Surgical Plan VR environment (ImmersiveTouch Inc, Chicago, IL). The clinicians virtually selected appropriately sized craniofacial implants and placed the implants in the desired orientation. Various measurement tools are available to aid in clinical decision-making. The ideal location of craniofacial implants was set according to an orbital and auricular prosthetic reconstruction. The resultant VR plan was exported for 3DP. The patients were evaluated preoperatively and postoperatively using the proposed VRP treatment. The workflow's data accuracy was validated postoperatively by comparing posterative CT data and the proposed VRP. Analysis was performed using Mimics software (Materialise, Leuven, Belgium). RESULT: It takes, on average, 10 minutes to place 4 implants in the virtual reality space. The 3DP files resulting from VRP take ~2 hours to print and are constructed with a biocompatible resin appropriate for clinical use as surgical guides. Our user-friendly VRP workflow allows for an accurate simulation of surgical and nonsurgical procedures with an average displacement in XYZ of 0.6 mm and an SD of 0.3 mm. In addition, VRP is an excellent tool to simulate the craniofacial placement procedure and improves unsupervised self-learning teaching. CONCLUSION: VRP is an exciting tool for training clinicians and students in complex surgical procedures. This study shows the promising applicability and efficiency of VR in clinical planning and management of facial rehabilitation. Patients allowed to interact with VR have been engaged, which would aid their treatment acceptance and patient education. A valuable advantage of surgical simulation is the reduced costs associated with renting instruments, buying implant dummies, and surgical hardware. The authors will explore VR to plan and treat surgical and nonsurgical reconstructive procedures and improve soft tissue manipulation. This study outlines the development of an original platform and workflow for segmentation, preoperative planning, and digital design within a VR environment and the clinical use in reconstructive surgery and anaplastology.

Light-responsive benzobisthiazole as oxidase mimic for rapid determination of glutathione in food and vegetable.

Accurate determination of glutathione (GSH) in food and vegetable is significant to instruct the appropriate supplementation of GSH in the human body. Light-responsive enzyme mimics have been widely used in detecting GSH due to controllable temporal and spatial accuracy. However, exploring a potential organic mimic enzyme with excellent catalytic efficiency keeps challenging. Herein, a benzobisthiazole organic oxidase mimic was successfully prepared by a simple and low-cost method. Based on its high light-responsive oxidase-like activity, it was used for high reliable colorimetric determination of GSH in food and vegetable for only 1 min with a large linear range of 0.02-30 µM and a low detection limit of 5.3 nM. This study provides a novel strategy to obtain powerful light-responsive oxidase mimics and holds great potential for rapid and accurate detection of GSH in food and vegetables.

Airway changes in patients with unilateral cleft lip/palate (UCL/P) after maxillary advancement.

OBJECTIVES: To assess the effect on the retropalatal airway (RPA), retroglossal airway (RGA), and total airway (TA) volumes and cephalometrics (SNA, SNB, ANB, PP-SN, Occl-SN, N-A, A-TVL, B-TVL) after maxillary advancement orthognathic surgery in patients with unilateral cleft lip/palate (UCL/P) using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: The CBCT scans of 30 patients (13 males and 17 females, 17-20 years old) with UCL/P were evaluated at two time points: preoperative (T1) and postoperative (T2). The interval between T1 and T2 ranged from 9-14 weeks, except for two patients in whom the interval was 24 weeks. Intraexaminer reliability was measured with an intraclass correlation coefficient test. A paired t-test was used to compare the airway and cephalometric measurements between T1 and T2, with a P value of .05 being considered significant. RESULTS: From T1 to T2, significant increases were found in the volumes of RPA (from 9574 ± 4573 to 10,472 ± 4767, P = .019), RGA (from 9736 ± 5314 to 11,358 ± 6588, P = .019), and TA (from 19,121 ± 8480 to 21,750 ± 10,078, P = .002). In addition, the RGA (from 385 ± 134 to 427 ± 165, P = .020) and TA (from 730 ± 213 to 772 ± 238, P = .016) sagittal area increased significantly. For minimal cross-sectional area (MCA), only the RPA increased significantly (from 173 ± 115 to 272 ± 129, P = .002). All cephalometric changes were statistically significant between T1 and T2 except for SNB. CONCLUSIONS: Maxillary advancement in patients with UCL/P produces statistically significant increases in the retropalatal (volumetric and MCA), retroglossal (volumetric and sagittal), and total (volumetric and sagittal) airways based on data from CBCT imaging.

Carrier-Free Nano-PROTACs to Amplify Photodynamic Therapy Induced DNA Damage through BRD4 Degradation.

Therapy-induced DNA damage is the most common strategy to inhibit tumor cell proliferation, but the therapeutic efficacy is limited by DNA repair machinery. Carrier-free nanoproteolysis targeting chimeras (PROTACs), designed as SDNpros, have been developed to enhance photodynamic therapy (PDT) by blocking the DNA damage repair pathway through BRD4 degradation. Specifically, SDNpros are constructed through noncovalent interactions between the photosensitizer of chlorine e6 (Ce6) and PROTACs of BRD4 degrader (dBET57) via self-assembly. SDNpro has favorable dispersibility and a uniform nanosize distribution without drug excipients. Upon light irradiation, SDNpro produces abundant reactive oxygen species (ROS) to induce DNA oxidative damage. Meanwhile, the DNA repair pathway would be interrupted by the concurrent degradation of BRD4, which could intensify the oxidative DNA damage and elevate PDT efficiency. Beneficially, SDNpro suppresses tumor growth and avoids systemic side effects, providing a promising strategy to promote the clinical translation of PROTACs for tumor treatment.

Coordination-Driven Self-Assembly of Biomedicine to Enhance Photodynamic Therapy by Inhibiting Proteasome and Bcl-2.

Tumor cells resist oxidative damage and apoptosis by activating defense mechanisms. Herein, a self-delivery biomedicine (designated as BSC) is developed by the self-assembly of Bortezomib (BTZ), Sabutoclax (Sab) and Chlorin e6 (Ce6). Interestingly, BTZ can be coordinated with Sab to promote the assembly of uniform ternary biomedicine through non-covalent intermolecular interactions. Moreover, BTZ as a proteasome inhibitor can prevent tumor cells from scavenging damaged proteins to reduce their oxidative resistance. Sab can downregulate B-cell lymphoma 2 (Bcl-2) to decrease the antiapoptotic protein. Both the proteasome and Bcl-2 inhibitions contribute to increasing cell apoptosis and amplifying photodynamic therapy (PDT) efficacy of Ce6. Encouragingly, carrier-free BSC receives all biological activities of these assembly elements, including photodynamic performance as well as inhibitory capabilities of proteasome and Bcl-2. Besides, BSC has a preferable cellular uptake ability and tumor retention property, which increase the drug delivery efficiency and bioavailability. In vitro and in vivo research demonstrate the superior PDT efficiency of BSC by proteasome and Bcl-2 inhibitions. Of special note, the coordination-driven self-assembly of BSC is pH-responsive, which can be disassembled for controlled drug release upon tumor acidic microenvironment. This study will expand the applicability of self-delivery nanomedicine with sophisticated mechanisms for tumor treatment.

Paraptosis Inducer to Effectively Trigger Immunogenic Cell Death for Metastatic Tumor Immunotherapy with IDO Inhibition.

Paraptosis is characterized by the extensive vacuolization of endoplasmic reticulum (ER) and mitochondria, which will cause the release of damage-associated molecular patterns to promote immunogenic cell death (ICD). However, the tumor can develop an immunosuppressive microenvironment to affect the ICD activation for the purpose of immune escape. Herein, a paraptosis inducer (CMN) is constructed to amplify the ICD effect for efficient immunotherapy by inhibiting the activity of indoleamine 2,3-dioxygenase (IDO). Initially, CMN is prepared by the assembly of copper ions (Cu2+), morusin (MR), and IDO inhibitor (NLG919) through noncovalent interactions. Without the need for extra drug carriers, CMN possesses very high drug contents and exhibits a favorable GSH responsiveness for disassembly. Subsequently, the released MR can trigger paraptosis to cause extensive vacuolization of ER and mitochondria, contributing to activating ICD for immunotherapy. Moreover, NLG919 would inhibit IDO to remodel the tumor microenvironment and promote the activation of cytotoxic T cells, leading to an intensive antitumor immunity. Abundant in vivo studies indicate that CMN is superior in suppressing the proliferations of not only primary tumor but also metastatic and rechallenged tumors. Such a GSH-responsive paraptosis inducer might provide a promising strategy to trigger ICD and enhance tumor immunotherapy.

Targeting glutamine metabolism with photodynamic immunotherapy for metastatic tumor eradication.

Immune checkpoint blockade (ICB) has shown significant clinical success, yet its responses can vary due to immunosuppressive tumor microenvironments. To enhance antitumor immunity, combining ICB therapy with tumor metabolism reprogramming may be a promising strategy. In this study, we developed a photodynamic immunostimulant called BVC aiming to boost immune recognition and prevent immune escape for metastatic tumor eradication by reprogramming glutamine metabolism. BVC, a carrier free self-assembled nanoparticle, comprises a photosensitizer (chlorin e6), an ASCT2 inhibitor (V9302) and a PD1/PDL1 blocker (BMS-1), offering favorable stability and enhanced drug delivery efficiency. The potent photodynamic therapy (PDT) capability of BVC is attributed to its regulation of glutamine metabolism, which influences the redox microenvironment within tumor tissues. By targeting ASCT2-mediated glutamine metabolism, BVC inhibits glutamine transport and GSH synthesis, leading to the upregulation of Fas and PDL1. Additionally, BVC-mediated PDT induces immunogenic cell death, triggering a cascade of immune responses. Consequently, BVC not only enhances immune recognition between CD8+ T cells and Fas-overexpressing tumor cells but also reduces tumor cell immune escape through PD1/PDL1 blockade, significantly benefiting metastatic tumor eradication. This study paves a novel approach for multi-synergistic tumor treatment.

Virtual Reality and Augmented Reality in Plastic and Craniomaxillofacial Surgery: A Scoping Review.

Virtual reality (VR) and augmented reality (AR) have evolved since their introduction to medicine in the 1990s. More powerful software, the miniaturization of hardware, and greater accessibility and affordability enabled novel applications of such virtual tools in surgical practice. This scoping review aims to conduct a comprehensive analysis of the literature by including all articles between 2018 and 2021 pertaining to VR and AR and their use by plastic and craniofacial surgeons in a clinician-as-user, patient-specific manner. From the initial 1637 articles, 10 were eligible for final review. These discussed a variety of clinical applications: perforator flaps reconstruction, mastectomy reconstruction, lymphovenous anastomosis, metopic craniosynostosis, dermal filler injection, auricular reconstruction, facial vascularized composite allotransplantation, and facial artery mapping. More than half (60%) involved VR/AR use intraoperatively with the remainder (40%) examining preoperative use. The hardware used predominantly comprised HoloLens (40%) and smartphones (40%). In total, 9/10 Studies utilized an AR platform. This review found consensus that VR/AR in plastic and craniomaxillofacial surgery has been used to enhance surgeons' knowledge of patient-specific anatomy and potentially facilitated decreased intraoperative time via preoperative planning. However, further outcome-focused research is required to better establish the usability of this technology in everyday practice.

Patient-specific Composite Anatomic Models: Improving the Foundation for Craniosynostosis Repair.

Preoperative surgical planning incorporating computer-aided design and manufacturing is increasingly being utilized today within the fields of craniomaxillofacial, orthopedic, and neurosurgery. Application of these techniques for craniosynostosis reconstruction can include patient-specific anatomic reference models, "normal" reference models or patient-specific cutting/marking guides based on the presurgical plan. The major challenge remains the lack of tangible means to transfer the preoperative plan to the operating table. We propose a simple solution to utilize a digitally designed, 3D-printed "composite model" as a structural template for cranial vault reconstruction. The composite model is generated by merging the abnormal patient cranial anatomy with the "dural surface topography" of an age-matched, sex-matched, and ethnicity-matched normative skull model. We illustrate the applicability of this approach in 2 divergent cases: 22-month-old African American male with sagittal synostosis and 5-month-old White male with metopic synostosis. The aim of this technical report is to describe our application of this computer-aided design and modeling workflow for the creation of practical 3D-printed skulls that can serve as intraoperative frameworks for the correction of craniosynostosis. With success in our first 2 cases, we believe this approach of a composite model is another step in reducing our reliance on subjective guesswork, and the fundamental aspect of the workflow has a wider application within the field of craniofacial surgery for both clinical patient care and education.

N4-acetylcytidine modification of lncRNA CTC-490G23.2 promotes cancer metastasis through interacting with PTBP1 to increase CD44 alternative splicing.

Although N4-acetylcytidine (ac4C) modification affects the stability and translation of mRNA, it is unknown whether it exists in noncoding RNAs, and its biological function is unclear. Here, nucleotide-resolution method for profiling CTC-490G23.2 ac4C sites and gain- and loss-of-function experiments revealed that N-acetyltransferase 10 (NAT10) is responsible for ac4C modification of long noncoding RNAs (lncRNAs). NAT10-mediated ac4C modification leads to the stabilization and overexpression of lncRNA CTC-490G23.2 in primary esophageal squamous cell carcinoma (ESCC) and its further upregulation in metastatic tissues. CTC-490G23.2 significantly promotes cancer invasion and metastasis in vitro and in vivo. Mechanistically, CTC-490G23.2 acts as a scaffold to increase the binding of CD44 pre-mRNA to polypyrimidine tract-binding protein 1 (PTBP1), resulting in a oncogenic splicing switch from the standard isoform CD44s to the variant isoform CD44v(8-10). CD44v(8-10), but not CD44s, binds to and increases the protein stability of vimentin. Expression levels of CTC-490G23.2 and CD44v(8-10) can predict poor prognosis in cancer patients. Furthermore, the antisense oligonucleotide (ASO)/SV40-LAH4-L1 peptide self-assembled nanocomplexes targeting CTC490G23.2 exerts a significantly suppressive effect on cancer metastasis. The outcome of this study will provide new mechanistic insight into the ac4C modification of lncRNAs and useful clues for the development of novel systemic therapies and prognostic biomarkers.