Biosynthesis of the highly oxygenated tetracyclic core skeleton of Taxol.

Taxol is a widely-applied anticancer drug that inhibits microtubule dynamics in actively replicating cells. Although a minimum 19-step biosynthetic pathway has been proposed and 16 enzymes likely involved have been characterized, stepwise biosynthetic reactions from the well-characterized di-oxygenated taxoids to Taxol tetracyclic core skeleton are yet to be elucidated. Here, we uncover the biosynthetic pathways for a few tri-oxygenated taxoids via confirming the critical reaction order of the second and third hydroxylation steps, unearth a taxoid 9α-hydroxylase catalyzing the fourth hydroxylation, and identify CYP725A55 catalyzing the oxetane ester formation via a cascade oxidation-concerted acyl rearrangement mechanism. After identifying a acetyltransferase catalyzing the formation of C7-OAc, the pathway producing the highly-oxygenated 1ß-dehydroxybaccatin VI with the Taxol tetracyclic core skeleton is elucidated and its complete biosynthesis from taxa-4(20),11(12)-diene-5α-ol is achieved in an engineered yeast. These systematic studies lay the foundation for the complete elucidation of the biosynthetic pathway of Taxol.

Evaluation of neck control strategies for oral squamous cell carcinoma of stage I: Neck dissection or potential immunotherapy.

The neck control strategies of early-stage oral squamous cell carcinoma (OSCC) patients with clinical node-negative neck remain uncertain. These patients could be benefit from elective neck dissection (END) alongside primary tumor excision; but current evidence on END versus observation for OSCC of stage I only is not yet analyzed collectively in detail. Herein, this short communication aimed to evaluate the neck control strategies of stage I OSCC, mainly END versus observation. A total of 740 patients with stage I OSCC, comprising 434 underwent END and 306 received observation, were identified from literature. The results showed that stage I OSCC patients would not be benefit from END based on the analysis of neck nodal recurrence and overall survival. An ideal strategy would likely be to avoid neck dissection for stage I OSCC patients with N0 neck. Immune checkpoint therapy is such a potential strategy, which aims at eliciting potent antitumor immune responses within lymph nodes hold promise for treating patients with early-stage OSCC and may prove more efficacious than lymphadenectomy in a variety of scenarios. Consequently, neck dissection for stage I OSCC could be approached with caution, particularly in patients receiving immune checkpoint therapy.

Biosynthesis of the Plant Coumarin Osthole by Engineered Saccharomyces cerevisiae.

Osthole is a coumarin compound found in the traditional Chinese medicine Cnidium monnieri. Extensive studies have shown that osthole exhibits many medicinal properties, and recently, researchers have found that it possesses potent airway-relaxation activity by inhibiting phosphodiesterase 4D activity, making it a potential novel bronchodilator that does not target ß2-adrenoceptors for asthma treatment. Here, we report the complete biosynthesis of osthole in engineered yeast. We created an umbelliferone (UMB)-producing strain by reconstituting the complete UMB pathway in yeast. We found that coumarin synthase (COSY) is essential for the conversion of 2',4'-dihydroxycinnamoyl-CoA into UMB in yeast; this conversion has been treated as a spontaneous step in previously reported UMB-producing microbials. By introducing downstream prenyltransferase and methyltransferase genes and addressing problems such as protein expression and cofactor supply to fulfill the downstream steps, complete biosynthesis of osthole was achieved. Finally, through metabolic engineering, to ensure precursor supply, and the debugging of rate-limited steps, the osthole titer reached 108.10 mg/L in shake flasks and 255.1 mg/L in fed-batch fermentation. Our study is the first to produce osthole using engineered microbes, providing a blueprint for the supply of plant-derived osthole via microbial fermentation, which will remove the barriers of resource limitations for osthole-based drug development.

Coded aperture snapshot spectral imaging fundus camera.

Spectral imaging holds great promise for the non-invasive diagnosis of retinal diseases. However, to acquire a spectral datacube, conventional spectral cameras require extensive scanning, leading to a prolonged acquisition. Therefore, they are inapplicable to retinal imaging because of the rapid eye movement. To address this problem, we built a coded aperture snapshot spectral imaging fundus camera, which captures a large-sized spectral datacube in a single exposure. Moreover, to reconstruct a high-resolution image, we developed a robust deep unfolding algorithm using a state-of-the-art spectral transformer in the denoising network. We demonstrated the performance of the system through various experiments, including imaging standard targets, utilizing an eye phantom, and conducting in vivo imaging of the human retina.

Coded aperture snapshot spectral imaging fundus camera.

Spectral imaging holds great promise for the non-invasive diagnosis of retinal diseases. However, to acquire a spectral datacube, conventional spectral cameras require extensive scanning, leading to a prolonged acquisition. Therefore, they are inapplicable to retinal imaging because of the rapid eye movement. To address this problem, we built a coded aperture snapshot spectral imaging fundus camera, which captures a large-sized spectral datacube in a single exposure. Moreover, to reconstruct a high-resolution image, we developed a robust deep unfolding algorithm using a state-of-the-art spectral transformer in the denoising network. We demonstrated the system performance on both standard targets and an eye phantom.

Endoscopic Removal of a Retained Throat Pack: A Profound Lesson.

Throat packing/pharyngeal packing is typically applied in all oral and maxillofacial surgeries. It prevents the entry of saliva, blood, disinfectant, other liquids, and oral foreign objects (brackets) into the trachea or esophagus. The retention of throat packing results in severe complications such as airway obstruction and digestive tract symptoms. We present a case of postextubation throat pack ingestion. The pack was identified and retrieved successfully from the gastrointestinal tract.

Three-Dimensional-Printed Splint for Use in Pediatric Mandibular Fracture.

Mandibular fractures are the most common type, accounting for about 71% of facial fractures in children. The mandible is the only movable bone in the craniomaxillofacial region. The injury of the mandible has a serious impact on the functions of children's mouth opening, chewing, pronunciation, and occlusion. Therefore, the treatment of children's mandibular fractures is particularly important. Because of the characteristics of children with permanent tooth germ blocking and strong skeletal development, the treatment methods of adults cannot simply be used in children with mandibular fractures. Here, we demonstrate the simple, reliable method using 3-dimensional-printing splint for stability of the fracture segments in pediatric patients.

Preliminary Study of the Treatment Strategy for Retaining Traumatic Foreign Bodies Involving the Carotid Artery.

PURPOSE: Craniomaxillofacial trauma is usually accompanied by indwelling foreign bodies, and some of those are close to the carotid artery, which increases the risks and difficulties of surgical treatment. The introduction of interventional radiology combined with image-guided surgical navigation may be a good solution for precise surgery to remove foreign bodies. PATIENTS AND METHODS: Four patients were included in the study. All patients underwent digital subtraction angiography and enhanced computed tomography before surgery. The patients were divided into 3 categories (A, B, and C) according to the presence of carotid artery damage and its positional relationship with the foreign body, and 3 corresponding treatment strategies were developed. Treatments were completed using interventional radiology and surgical navigation systems. RESULTS: All foreign bodies were completely removed, except for 1 remaining in the jugular foramen in a patient. The prognosis of all patients was good, and no systemic complications occurred. CONCLUSION: The combined interventional radiology and surgical navigation method proposed in this study is an effective method to improve the accuracy and safety of foreign body removal surgery.

OCCS Classification and Treatment Algorithm for Comminuted Mandibular Fractures Based on 109 Patients and 11 Years Experiences: A Retrospective Study.

Comminuted mandibular fractures (CMFs) pose significant challenges to surgeons for their serious complications and poor outcomes. We aimed at proposing a classification with treatment algorithm of each category for CMFs. Patients with CMFs were retrospectively reviewed and classified into five categories: Type I: relatively good occlusion, no or slightly displaced fragments, no continuity destruction or bone defect; Type II: relatively good occlusion, damaged morphology, low comminution degree but intact continuity without bone defect; Type III: damaged morphology and higher comminution degree with intact continuity and relatively good occlusion; Type IV: high comminution, impaired continuity and poor occlusion without segmental bone defect; Type V: segmental bone defect. Conservative treatment, open reduction and internal fixation or microvascular osteocutaneous free flap transplantation was performed, accordingly. Demographics, perioperative data, complications and reasons for reoperations were recorded. The chi-square test was used for statistical analysis. In total, 109 patients were included in the study. After surgery, in the following group, 5 manifested infections, 1 manifested bone non-union, and 2 experienced reoperations, while in the unfollowing group, 10 manifested infections, 5 manifested bone non-union and 8 experienced reoperations. The OCCS classification and algorithm for CMFs achieve better outcomes and with lower complication rate.

Label-free hyperspectral imaging and deep-learning prediction of retinal amyloid ß-protein and phosphorylated tau.

Alzheimer's disease (AD) is a major risk for the aging population. The pathological hallmarks of AD-an abnormal deposition of amyloid ß-protein (Aß) and phosphorylated tau (pTau)-have been demonstrated in the retinas of AD patients, including in prodromal patients with mild cognitive impairment (MCI). Aß pathology, especially the accumulation of the amyloidogenic 42-residue long alloform (Aß42), is considered an early and specific sign of AD, and together with tauopathy, confirms AD diagnosis. To visualize retinal Aß and pTau, state-of-the-art methods use fluorescence. However, administering contrast agents complicates the imaging procedure. To address this problem from fundamentals, ex-vivo studies were performed to develop a label-free hyperspectral imaging method to detect the spectral signatures of Aß42 and pS396-Tau, and predicted their abundance in retinal cross-sections. For the first time, we reported the spectral signature of pTau and demonstrated an accurate prediction of Aß and pTau distribution powered by deep learning. We expect our finding will lay the groundwork for label-free detection of AD.

Identification of a novel multifunctional oxidosqualene cyclase from Zea mays sheds light on the biosynthetic pathway of three pentacyclic triterpenoids.

Zea mays (maize) is an important agricultural crop that produces a variety of valuable terpenoids, including several triterpenoids. However, no oxidosqualene cyclase (OSC) enzymes, which catalyze the first step in triterpenoid biosynthesis, have been identified in maize. Here, we identified a novel OSC (ZmOSC1) in maize using a combination of genomic mining and phylogenetic analyses. To functionally characterize the candidate OSC, we constructed a yeast strain that produced high levels of 2,3-oxidosqualene. When ZmOSC1 was expressed in this strain, three compounds were detected and identified as hop-17(21)-en-3-ol, hopenol B and simiarenol, respectively. For their biosynthesis, we proposed a potential cyclization mechanism catalyzed by ZmOSC1 via the generation of a dammarenyl cation, followed by sequential cationic ring expansion, cyclization, cationic migration and further proton elimination. This study discovered and characterized an OSC from maize for the first time, and laid a foundation to produce three bioactive pentacyclic triterpenes, hop-17(21)-en-3-ol, hopenol B and simiarenol, using synthetic biology approaches.

Three-Dimensional Printed Customized Surgical Guides for the Precise Correction of Complex Midfacial Post-Traumatic Deformities.

PURPOSE: The introduction of intraoperative computed tomography and image-guided navigation have demonstrated some advantages for the correction of midfacial post-traumatic deformities. However, these methods still do not achieve satisfactory results. The authors sought to describe a novel method for the precise correction of complex midfacial post-traumatic deformities using three-dimensional printing customized surgical guides. METHODS: Ten patients with midfacial post-traumatic deformities admitted between January 15, 2018 and August 20, 2020 were included. To design the surgical guide for each patient, preoperative planning and simulation datasets were used as a virtual template. Each surgical guide comprised three-dimensional printing cutting guides and customized titanium plates to guide the osteotomy and repositioning of the fracture fragments intraoperatively. Reduction and fixation were confirmed by intraoperative navigation. Postoperative deviation chromatography analysis and clinical examination were conducted to evaluate the surgical outcome. All operations were successfully performed. RESULTS: The average difference between the virtual plans and postoperative results was less than 1.5 mm. The 3- to 6-month follow-up evaluation demonstrated that symptoms were alleviated, and postoperative function and esthetics improved considerably. CONCLUSIONS: Three-dimensional-printed customized surgical guides can accurately and effectively transfer the virtual surgical plan to the patient and could be considered an ideal and valuable option for this potentially complicated procedure.

Introduction of Digital-Assisted Multidisciplinary Treatment in the Functional and Morphological Reconstruction of Naso-Orbital-Ethmoid Fractures.

ABSTRACT: This study summarizes the process of digital-assisted multidisciplinary treatment (MDT) of naso-orbital-ethmoid (NOE) fractures and evaluates the treatment outcomes. From October 2018 to December 2020, 39 patients with NOE fractures were treated in our department, 21 of whom were diagnosed and treated by a multidisciplinary team. After preoperative multidisciplinary discussions and personalized virtual surgical planning, they received MDT with the assistance of a surgical navigation system. The other 18 patients received traditional single-disciplinary treatment, that is, no preoperative multidisciplinary discussions. Oral and maxil-lofacial surgeons performed surgical design and digitally-assisted surgery alone. After the operation, treatment outcomes were evaluated in terms of aesthetic appearance and function. The duration of preoperative preparation and postoperative aesthetic outcomes were not significantly different in patients who received single-disciplinary treatment and MDT ( P > 0.05). However, postoperative functional outcomes were significantly better in patients who received MDT ( P < 0.05). Furthermore, no significant complications were found. Digital-assisted MDT has a high application value in repair and appearance reconstruction, especially restoring functionality after NOE fracture; thus, it should be promoted in clinical practice.

Classifying and standardizing panfacial trauma according to anatomic categories and Facial Injury Severity Scale: a 10-year retrospective study.

BACKGROUND: The purpose of this study was to identify the epidemiologic factors of panfacial fractures (PFs), and to evaluate the significance of anatomic PF categories and the Facial Injury Severity Scale (FISS) in classifying and standardizing panfacial injuries. METHODS: A retrospective review of all patients treated with PFs at our institution between June 2010 and April 2021 was performed. PF was defined as a concurrent fracture in at least 3 of 4 facial subunits (frontal, upper midface, lower midface, and mandible). Data regarding patient demographics, causes of injury, location of fractures, major concomitant injuries, and postinjury complications were collected, and the FISS score was collected from each patient. Statistical analysis was performed using IBM SPSS Statistics version 22.0. RESULTS: A total of 227 patients were enrolled. The most commonly fractured bones were the maxillary sinus wall (92.1%), mandible (82.8%), and zygomatic arch (75.3%), and the most common fracture sites in PFs were graphically presented. Four PF patterns were defined: FULM (n = 60), FUL (n = 39), ULM (n = 127), and FUM (n = 1). There was a significant association between PF patterns and sex (p = 0.018), the number of concomitant injuries (p = 0.014), and early surgical airway management (p = 0.003). Different PF patterns were significantly correlated with different types of concomitant injuries and complications. The FISS score showed a significant difference with PF patterns (p = 0.000) and sex (p = 0.007), and a FISS value of 11 or more is the appropriate cutoff for the prediction of multiple concomitant injuries and complications. CONCLUSIONS: Both the anatomic PF categories and FISS were significantly correlated with various concomitant injuries and complications. The combination of PF categories and FISS provided a better positive and negative prediction of concomitant injuries and complications for PF patients. Patients with FULM and FISS > 11 had an obviously higher proportion of the need for multiprofessional treatment.

Proposal for the Fusion of Ultrasound and Computed Tomography Images for Image Shift Correction in Craniomaxillofacial Soft Tissue Surgery.

ABSTRACT: Surgical navigation has greatly improved the accuracy of craniomaxillofacial bone surgery and is widely used in the clinic. However, during surgery, craniomaxillofacial soft tissue is always deformed due to traction and compression, which leads to intraoperative image drift. This, in turn, impacts navigation accuracy. In order to improve navigation accuracy, this technical note presents a preliminary proposal for fusion imaging technology, which combines ultrasound and computed tomography to address navigational image drift in craniomaxillofacial soft tissue surgery.

The unprecedented diversity of UGT94-family UDP-glycosyltransferases in Panax plants and their contribution to ginsenoside biosynthesis.

More than 150 ginsenosides have been isolated and identified from Panax plants. Ginsenosides with different glycosylation degrees have demonstrated different chemical properties and bioactivity. In this study, we systematically cloned and characterized 46 UGT94 family UDP-glycosyltransferases (UGT94s) from a mixed Panax ginseng/callus cDNA sample with high amino acid identity. These UGT94s were found to catalyze sugar chain elongation at C3-O-Glc and/or C20-O-Glc of protopanaxadiol (PPD)-type, C20-O-Glc or C6-O-Glc of protopanaxatriol (PPT)-type or both C3-O-Glc of PPD-type and C6-O-Glc of PPT-type or C20-O-Glc of PPD-type and PPT-type ginsenosides with different efficiencies. We also cloned 26 and 51 UGT94s from individual P. ginseng and P. notoginseng plants, respectively; our characterization results suggest that there is a group of UGT94s with high amino acid identity but diverse functions or catalyzing activities even within individual plants. These UGT94s were classified into three clades of the phylogenetic tree and consistent with their catalytic function. Based on these UGT94s, we elucidated the biosynthetic pathway of a group of ginsenosides. Our present results reveal a series of UGTs involved in second sugar chain elongation of saponins in Panax plants, and provide a scientific basis for understanding the diverse evolution mechanisms of UGT94s among plants.

New Solutions to Improve the Accuracy of the Navigation-Guided Foreign Body Removal in Craniomaxillofacial Deep Space.

OBJECTIVE: Surgical navigation-guided removal of foreign bodies in the craniomaxillofacial region has been proven to be an effective method. However, there have been some unsuccessful patients due to reduced navigation accuracy or complicated and undetectable anatomy. This article summarizes the experience and proposes some solutions to achieve better results. STUDY DESIGN: Two solutions were proposed to optimize the surgical navigation procedure: using a 3-dimensionally printed customized mandible retainer to indirectly maintain the consistency of the foreign body's visual images of preoperative planning and intraoperative navigation and importing real-time endoscopic imaging during surgery to provide vision under complex anatomy. Two patients were selected for each method. RESULTS: The foreign bodies were successfully and minimally invasively removed in all patients assisted by optimized surgical navigation. During follow-up at 3 to 6 months postoperatively, no complications were found. CONCLUSION: Improving navigation accuracy and providing real vision might be effective at compensating for insufficient navigation due to navigation positioning errors or the interference of imperceptible and complicated anatomy.

Dermoid Cyst of the Parotid Gland Location.

Dermoid cysts (DCs) can occur anywhere in the body. However, DCs on neck or head are not common, which account for about 7% among all kinds of DCs and mostly occur in superficial areas. These cysts are hardly seen in the parotid gland. It is challenging to make accurate diagnosis before surgery because of its rarity and the ambiguous findings on radiology images. Based on a short review of the literature on DCs in the parotid gland, we discussed their clinical features and histopathological and radiological characteristics.

Hyperspectrally Compressed Ultrafast Photography.

The spatial, temporal, and spectral information in optical imaging play a crucial role in exploring the unknown world and unencrypting natural mysteries. However, the existing optical imaging techniques can only acquire the spatiotemporal or spatiospectral information of the object with the single-shot method. Here, we develop a hyperspectrally compressed ultrafast photography (HCUP) that can simultaneously record the spatial, temporal, and spectral information of the object. In our HCUP, the spatial resolution is 1.26 lp/mm in the horizontal direction and 1.41 lp/mm in the vertical direction, the temporal frame interval is 2 ps, and the spectral frame interval is 1.72 nm. Moreover, HCUP operates with receive-only and single-shot modes, and therefore it overcomes the technical limitation of active illumination and can measure the nonrepetitive or irreversible transient events. Using our HCUP, we successfully measure the spatiotemporal-spatiospectral intensity evolution of the chirped picosecond laser pulse and the photoluminescence dynamics. This Letter extends the optical imaging from three- to four-dimensional information, which has an important scientific significance in both fundamental research and applied science.