Genome-wide analysis of the ERF Family in Stephania japonica provides insights into the regulatory role in Cepharanthine biosynthesis.

Introduction: Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid (bisBIA) extracted from Stephania japonica, has received significant attention for its anti-coronavirus properties. While ethylene response factors (ERFs) have been reported to regulate the biosynthesis of various alkaloids, their role in regulating CEP biosynthesis remains unexplored. Methods: Genome-wide analysis of the ERF genes was performed with bioinformatics technology, and the expression patterns of different tissues, were analyzed by transcriptome sequencing analysis and real-time quantitative PCR verification. The nuclear-localized ERF gene cluster was shown to directly bind to the promoters of several CEP-associated genes, as demonstrated by yeast one-hybrid assays and subcellular localization assays. Results: In this work, 59 SjERF genes were identified in the S. japonica genome and further categorized into ten subfamilies. Notably, a SjERF gene cluster containing three SjERF genes was found on chromosome 2. Yeast one-hybrid assays confirmed that the SjERF gene cluster can directly bind to the promoters of several CEP-associated genes, suggesting their crucial role in CEP metabolism. The SjERFs cluster-YFP fusion proteins were observed exclusively in the nuclei of Nicotiana benthamiana leaves. Tissue expression profiling revealed that 13 SjERFs exhibit high expression levels in the root, and the qRT-PCR results of six SjERFs were consistent with the RNA-Seq data. Furthermore, a co-expression network analysis demonstrated that 24 SjERFs were highly positively correlated with the contents of various alkaloids and expression levels of CEP biosynthetic genes. Conclusion: This study provides the first systematic identification and analysis of ERF transcription factors in the S.japonica genome, laying the foundation for the future functional research of SjERFs transcription factors.

[Accurate repair of oral and maxillofacial soft tissue defects with ulnar artery flap].

Objective: To investigate the characteristics of the clinical application of ulnar artery flap in the repair of oral and maxillofacial soft tissue defects. Methods: The clinical data of 12 patients with oral and maxillofacial defects repaired with ulnar artery flap between June 2021 and July 2023 was retrospectively analyzed. Among them, 11 cases were male and 1 case was female; their ages ranged from 28 to 76 years, with a mean age of 54.8 years. The lesions were located in the lateral margin of the tongue in 3 cases, the root of the tongue in 2 cases, the base of the tongue in 4 cases, and the buccal region, upper gingiva, and lower lip in 1 case each. The pathological types were squamous cell carcinoma in 11 cases and adenoid cystic carcinoma in 1 case; according to the TNM staging of the International Union Against Cancer (UICC), there were 5 cases of T 3N 0M 0, 2 cases of T 3N 1M 0, 1 case of T 4aN 0M 0, 1 case of T 4aN 1M 0, 1 case of T 4aN 2bM 0, and 2 cases of T 4aN 2cM 0. After complete resection of the lesion, the defect ranged from 6 cm×3 cm to 8 cm×5 cm. Preoperatively, colour Doppler ultrasound was used to detect the non-dominant forearm, measure the thickness of the subcutaneous fat in the donor area, confirm and mark the ulnar artery and reflux vein, and measure the diameter of the vessels, flow velocity, and the perforator position; intraoperatively, the flap was designed, prepared, anastomosed, and positioned according to the corresponding data. The vessels were all anastommosed with one artery and two veins to form a super-reflux. After complete hemostasis, the defects were repaired with sliding flap (2 cases), direct suture (4 cases), biomembrane (2 cases), or razor thin skin graft (4 cases). Results: No vascular crisis occurred after operation, and all the flaps survived in 12 cases. Wounds in the donor site healed by first intention in 10 cases and by second intention in 2 cases. Wounds in the recipient site healed by first intention in all cases. All 12 patients were followed up 5-18 months, with an average of 11.4 months. The colour and texture of the flap were normal. The function of hand and upper limb was evaluated according to the trial standard of upper limb function assessment of the Chinese Society of Hand Surgery of the Chinese Medical Association, and the score was 65-81 (mean, 71.3), and achieved excellent in 1 case and good in 11 cases. The score of Oral Health Impact Scale (OHIP) was 9-18, with an average of 14.2, and the oral function was satisfactory. During the follow-up, 1 case had local recurrence and underwent extended resection again, while the other patients had no recurrence or metastasis. Conclusion: For moderate soft tissue defects with complex oral and maxillofacial function, ulnar artery flap repair is effective.

Do red tide events promote an increase in zooplankton biodiversity?

Red tides occurring off the southern coast of Korea impact the marine ecosystem and aquaculture industries. Zooplankton are crucial in the food web, connecting primary producers to higher predators and interact diversely with red tide organisms. This study explores dynamics of the zooplankton community over seven years including three red tide and four non-red tide years in Tongyeong using metabarcoding. In non-red tide years, zooplankton diversity showed typical seasonal patterns, increasing from June to early October. However, during red tide years, diversity remained high, with a shift in species composition-decreased Copepoda and increased Branchiopoda, Echinodermata, Malacostraca, and Annelida. Diversity indices were significantly higher in red tide years across all periods except for the richness in "after" that showed an insignificant higher value. The differences in zooplankton assemblages across periods were influenced by surface temperatures and the density of the red tide-causing alga Margalefidinium polykrikoides. Eight species emerged as indicator species and showed direct correlations with M. polykrikoides and among them, seven species were indicator species for red tide occurrence years. The ecological characteristics of M. polykrikoides blooms and their recurrent occurrences over several decades suggest that zooplankton may adapt to the toxins and use these blooms as spawning cues. Overall, this study provides comprehensive understanding on changes in zooplankton communities during red tide events, offering novel insights into their ecology.

Equipoise Lost? Trial Conduct Challenges in an Era of Breakthrough Therapies.

FDA Oncology Center's @Falleh_Fallah and colleagues discuss loss of equipoise and other trial conduct challenges in an era of breakthrough therapies - via @JCO_ASCO.

Systemic immune-inflammation and prognostic immune nutritional index in oral squamous cell carcinoma patients.

Aim: To investigate the systemic immune-inflammation index and prognostic immune nutritional index in the prognostic evaluation of oral squamous cell carcinoma.Materials & methods: We analyzed retrospectively the relationship between systemic immune-inflammation index, prognostic immune nutritional index and clinicopathological variables and the overall survival of 262 patients who underwent radical surgery.Results: Multivariate analysis showed high systemic immune-inflammation index (Hazard ratio = 3.062, 95% CI: 1.021-8.251), low prognostic immune nutritional index (Hazard ratio = 0.297, 95% CI: 0.139-0.636), tumor node metastasis classification 3-4 (Hazard ratio = 9.862, 95% CI: 4.658-20.880) patients have worse overall survival.Conclusion: Preoperative systemic immune-inflammation index and prognostic immune nutritional index are independent risk factors for prognostic survival status in oral squamous cell carcinoma.

[Box: see text].

Asteraceae genome database: a comprehensive platform for Asteraceae genomics.

Asteraceae, the largest family of angiosperms, has attracted widespread attention for its exceptional medicinal, horticultural, and ornamental value. However, researches on Asteraceae plants face challenges due to their intricate genetic background. With the continuous advancement of sequencing technology, a vast number of genomes and genetic resources from Asteraceae species have been accumulated. This has spurred a demand for comprehensive genomic analysis within this diverse plant group. To meet this need, we developed the Asteraceae Genomics Database (AGD; http://cbcb.cdutcm.edu.cn/AGD/). The AGD serves as a centralized and systematic resource, empowering researchers in various fields such as gene annotation, gene family analysis, evolutionary biology, and genetic breeding. AGD not only encompasses high-quality genomic sequences, and organelle genome data, but also provides a wide range of analytical tools, including BLAST, JBrowse, SSR Finder, HmmSearch, Heatmap, Primer3, PlantiSMASH, and CRISPRCasFinder. These tools enable users to conveniently query, analyze, and compare genomic information across various Asteraceae species. The establishment of AGD holds great significance in advancing Asteraceae genomics, promoting genetic breeding, and safeguarding biodiversity by providing researchers with a comprehensive and user-friendly genomics resource platform.

Molecular Transformers: Adaptive Multitarget Ligands for Esterase-Induced Transition from Analgesics to Anesthetics.

Multitarget strategies are essential in addressing complex diseases, yet developing multitarget-directed ligands (MTDLs) is particularly challenging when aiming to engage multiple therapeutic targets across different tissues. Here, we present a molecular transformer strategy, enhancing traditional MTDLs. By utilizing esterase-driven hydrolysis, this approach mimics the adaptive nature of transformers for enabling molecules to modify their pharmacological effects in response to the biological milieu. By virtual screening and biological evaluation, we identified KGP-25, a novel compound initially targeting the voltage-gated sodium channel 1.8 (Nav1.8) in the peripheral nervous system (PNS) for analgesia, and later the γ-aminobutyric acid subtype A receptor (GABAA) in the central nervous system (CNS) for general anesthesia. Our findings confirm KGP-25's dual efficacy in cellular and animal models, effectively reducing opioid-related side effects. This study validates the molecular transformer approach in drug design and highlights its potential to overcome the limitations of conventional MTDLs, paving new avenues in innovative therapeutic strategies.

Identification of N-(((1S,3R,5S)-adamantan-1-yl)methyl)-3-((4-chlorophenyl)sulfonyl)benzenesulfonamide as novel Nav1.8 inhibitor with analgesic profile.

Chronic pain is a common and challenging clinical problem that significantly impacts patients' quality of life. The sodium channel Nav1.8 plays a crucial role in the occurrence and development of chronic pain, making it one of the key targets for treating chronic pain. In this article, we combined virtual screening with cell membrane chromatography techniques to establish a novel method for rapid high-throughput screening of selective Nav1.8 inhibitors. Using this approach, we identified a small molecule compound 6, which not only demonstrated high affinity and inhibitory activity against Nav1.8 but also exhibited significant inhibitory effects on CFA-induced chronic inflammatory pain. Compared to the positive drug VX-150, compound 6 showed a more prolonged analgesic effect, making it a promising candidate as a Nav1.8 inhibitor with potential clinical applications. This discovery provides a new therapeutic option for the treatment of chronic pain.

FDA Approval Summary: Durvalumab and Pembrolizumab, Immune Checkpoint Inhibitors for the Treatment of Biliary Tract Cancer.

On September 2, 2022, the Food and Drug Administration (FDA) approved durvalumab in combination with cisplatin and gemcitabine, for the treatment of patients with unresectable or metastatic biliary tract cancers (BTC). On October 31, 2023, the FDA approved pembrolizumab in combination with cisplatin and gemcitabine for the same indication. Approvals were based on two randomized, multiregional, placebo-controlled trials that randomly allocated patients to receive durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966) in combination with chemotherapy or placebo in combination with chemotherapy. Overall survival (OS) was the primary endpoint in both studies. In both studies, a statistically significant and clinically meaningful improvement in OS was demonstrated. In the TOPAZ-1 trial, the median OS of patients receiving durvalumab was 12.8 months [95% confidence interval (CI), 11.1-14.0] and 11.5 months (95% CI, 10.1-12.5) in patients receiving placebo [hazard ratio (HR), 0.80 (95% CI, 0.66-0.97)]. In the KEYNOTE-966 trial, the median OS of patients receiving pembrolizumab was 12.7 months (95% CI, 11.5-13.6) and 10.9 months (95% CI, 9.9-11.6) in patients receiving placebo [HR, 0.83 (95% CI, 0.72-0.95)]. The addition of checkpoint inhibitors to standard of care chemotherapy for this indication did not reveal any new adverse event signals, and the safety profile was generally consistent with the known clinical experience with durvalumab, pembrolizumab, and the backbone chemotherapy regimen. The approvals of durvalumab and pembrolizumab in combination with standard of care cisplatin and gemcitabine for the treatment of unresectable or metastatic BTC add two new therapeutic options for these patients.

An improved genome assembly of Chrysanthemum nankingense reveals expansion and functional diversification of terpene synthase gene family.

BACKGROUND: Terpenes are important components of plant aromas, and terpene synthases (TPSs) are the key enzymes driving terpene diversification. In this study, we characterized the volatile terpenes in five different Chrysanthemum nankingense tissues. In addition, genome-wide identification and expression analysis of TPS genes was conducted utilizing an improved chromosome-scale genome assembly and tissue-specific transcriptomes. The biochemical functions of three representative TPSs were also investigated. RESULTS: We identified tissue-specific volatile organic compound (VOC) and volatile terpene profiles. The improved Chrysanthemum nankingense genome assembly was high-quality, including a larger assembled size (3.26 Gb) and a better contig N50 length (3.18 Mb) compared to the old version. A total of 140 CnTPS genes were identified, with the majority representing the TPS-a and TPS-b subfamilies. The chromosomal distribution of these TPS genes was uneven, and 26 genes were included in biosynthetic gene clusters. Closely-related Chrysanthemum taxa were also found to contain diverse TPS genes, and the expression profiles of most CnTPSs were tissue-specific. The three investigated CnTPS enzymes exhibited versatile activities, suggesting multifunctionality. CONCLUSIONS: We systematically characterized the structure and diversity of TPS genes across the Chrysanthemum nankingense genome, as well as the potential biochemical functions of representative genes. Our results provide a basis for future studies of terpene biosynthesis in chrysanthemums, as well as for the breeding of improved chrysanthemum varieties.

Mitigating Gas Evolution in Electron Beam-Induced Gel Polymer Electrolytes Through Bi-Functional Cross-Linkable Additives.

The current high-capacity lithium-ion batteries (LIBs), reliant on flammable liquid electrolytes (LEs) and nickel-rich cathodes, are plagued by safety hazards, especially the risk of hazardous gas release stemming from internal side reactions. To address these safety concerns, an electron beam (E-beam)-induced gel polymer electrolyte (E-Gel) is introduced, employing dipentaerythritol hexaacrylate (DPH) as a bi-functional cross-linkable additive (CIA). The dual roles of DPH are exploited through a strategically designed E-beam irradiation process. Applying E-beam irradiation on the pre-cycled cells allows DPH to function as an additive during the initial cycle, establishing a protective layer on the surface of the anode and cathode and as a cross-linker during the E-beam irradiation step, forming a polymer framework. The prepared E-Gel with CIA has superior interfacial compatibility, facilitating lithium-ion diffusion at the electrode/E-Gel interface. The electrochemical assessment of 1.2 Ah pouch cells demonstrates that E-Gel substantially reduces gas release by 2.5 times compared to commercial LEs during the initial formation stage and ensures superior reversible capacity retention even after prolonged cycling at 55 °C. The research underscores the synergy of bifunctional CIA with E-beam technology, paving the way for large-scale production of safe, high-capacity, and commercially viable LIBs.

Carbon removal, sequestration and release by mariculture in an important aquaculture area, China.

To combat with climate change, most countries have set carbon neutrality target. However, our understanding on carbon removal, release and sequestration by mariculture remains unclear. Here, carbon removal, release and sequestration by maricultured seaweeds, shellfish and fish in Shandong Province during 2003-2022 were assessed using a comprehensive method that considers the processes of biological metabolism, seawater chemistry and carbon footprint. Saccharina japonica productivity has been largely enhanced since 2014, resulting in increased production and CO2 removal and sequestration. Seaweeds removed 172 Gg C and sequestered 62 Gg C in 2022. CO2 removal and release by shellfish demonstrated a slow increase trend, ranging from 231 to 374 Gg C yr-1 and 897 to 1438 Gg C yr-1 during 2003-2022, respectively. Contrary to seaweed and shellfish, maricultured fish added CO2 to seawater due to the use of feeds. The added CO2 by fish culture achieved the peak of 60 Gg C in 2011 and decreased to 25 Gg C in 2022. Most of this added CO2 was released to atmosphere by microbial mineralization and it was in the range of 21-52 Gg C yr-1 during 2003-2022. After summing up the contribution of seaweeds, shellfish and fish, both total CO2 removal (from 110 to 259 Gg C yr-1) and total CO2 release (from 929 to 1429 Gg C yr-1) increased remarkably during the past 20 years. To neutralize CO2 release by shellfish and fish, Pyropia yezoensis needs the largest culture area (1.65 ± 0.15 × 106 ha) while Gracilariopsis lemaneiformis requires the smallest area (0.11 ± 0.03 × 106 ha). In addition, there are enough available areas for culturing G. lemaneiformis, Ulva prolifera and Sargassum fusifarme to neutralize total CO2 emission in Shandong Province. This study elucidates carbon removal, release and sequestration capacities of mariculture and indicates that seaweed culture has a tremendous potential to achieve carbon neutrality target in Shandong.

Exosome Isolation Using Chitosan Oligosaccharide Lactate-1-Pyrenecarboxylic Acid-Based Self-Assembled Magnetic Nanoclusters.

Exosomes are small extracellular vesicles that play a crucial role in intercellular communication and offer significant potential for a wide range of biomedical applications. However, conventional methods for exosome isolation have limitations in terms of purity, scalability, and preservation of exosome structural integrity. To address these challenges, an exosome isolation platform using chitosan oligosaccharide lactate conjugated 1-pyrenecarboxylic acid (COL-Py) based self-assembled magnetic nanoclusters (CMNCs), is presented. CMNCs are characterized to optimize their size, stability, and interaction dynamics with exosomes. The efficiency of CMNCs in isolating exosomes is systematically evaluated using various analytical methods to demonstrate their ability to capture exosomes based on amphiphilic lipid bilayers. CMNC-based exosome isolation consistently yields exosomes with structural integrity and purity similar to those obtained using traditional methods. The reusability of CMNCs over multiple exosome isolation cycles underscores their scalability and offers an efficient solution for biomedical applications. These results are supported by western blot analysis, which demonstrated the superiority of CMNC-based isolation in terms of purity compared to conventional methods. By providing a scalable and efficient exosome isolation process that preserves both structural integrity and purity, CMNCs can constitute a new platform that can contribute to the field of exosome studies.

BASALT refines binning from metagenomic data and increases resolution of genome-resolved metagenomic analysis.

Metagenomic binning is an essential technique for genome-resolved characterization of uncultured microorganisms in various ecosystems but hampered by the low efficiency of binning tools in adequately recovering metagenome-assembled genomes (MAGs). Here, we introduce BASALT (Binning Across a Series of Assemblies Toolkit) for binning and refinement of short- and long-read sequencing data. BASALT employs multiple binners with multiple thresholds to produce initial bins, then utilizes neural networks to identify core sequences to remove redundant bins and refine non-redundant bins. Using the same assemblies generated from Critical Assessment of Metagenome Interpretation (CAMI) datasets, BASALT produces up to twice as many MAGs as VAMB, DASTool, or metaWRAP. Processing assemblies from a lake sediment dataset, BASALT produces ~30% more MAGs than metaWRAP, including 21 unique class-level prokaryotic lineages. Functional annotations reveal that BASALT can retrieve 47.6% more non-redundant opening-reading frames than metaWRAP. These results highlight the robust handling of metagenomic sequencing data of BASALT.

A haplotype-resolved gap-free genome assembly provides novel insight into monoterpenoid diversification in Mentha suaveolens 'Variegata'.

Mentha is a commonly used spice worldwide, which possesses medicinal properties and fragrance. These characteristics are conferred, at least partially, by essential oils such as menthol. In this study, a gap-free assembly with a genome size of 414.3 Mb and 31,251 coding genes was obtained for Mentha suaveolens 'Variegata'. Based on its high heterozygosity (1.5%), two complete haplotypic assemblies were resolved, with genome sizes of 401.9 and 405.7 Mb, respectively. The telomeres and centromeres of each haplotype were almost fully annotated. In addition, we detected a total of 41,135 structural variations. Enrichment analysis demonstrated that genes involved in terpenoid biosynthesis were affected by these structural variations. Analysis of volatile metabolites showed that M. suaveolens mainly produces piperitenone oxide rather than menthol. We identified three genes in the M. suaveolens genome which encode isopiperitenone reductase (ISPR), a key rate-limiting enzyme in menthol biosynthesis. However, the transcription levels of ISPR were low. Given that other terpenoid biosynthesis genes were expressed, M. suaveolens ISPRs may account for the accumulation of piperitenone oxide in this species. The findings of this study may provide a valuable resource for improving the detection rate and accuracy of genetic variants, thereby enhancing our understanding of their impact on gene function and expression. Moreover, our haplotype-resolved gap-free genome assembly offers novel insights into molecular marker-assisted breeding of Mentha.

A Pooled Analysis of Treatment-Free Survival in Advanced Renal Cell Carcinoma.

PURPOSE: A clinically meaningful attribute of some immune-oncology (IO) regimens is potential durable clinical benefit during a treatment-free interval. We characterize treatment-free survival (TFS) with and without ongoing toxicity in trials of frontline IO-VEGF tyrosine kinase inhibitor (TKI) combinations in patients with advanced renal cell carcinoma (aRCC). EXPERIMENTAL DESIGN: Individual patient data were pooled by treatment arm from randomized trials submitted to the FDA evaluating IO-TKI combination in treatment-naïve aRCC with at least 30 months of median follow-up. OS, TFS, TFS with and without toxicity, and time to all protocol therapy cessation were assessed. TFS was estimated by 30-month restricted mean times, defined as area between Kaplan-Meier curves for two time-to-event endpoints originating at randomization: time to all protocol therapy cessation and time to subsequent systemic therapy initiation or death. RESULTS: Three trials met criteria for analysis; 1,183 patients received IO-TKI versus 1,184 on control arms receiving TKI alone (sunitinib, SUN). IO-TKI and SUN groups spent 9% {2.7 months [95% confidence interval (CI), 1.8-3.5]} and 10% [2.9 months (95% CI, 2.1-3.8)] of the 30-month period alive and treatment-free, respectively. Mean TFS without grade ≥3 toxicity was 1.7 and 2.3 months in IO-TKI and SUN groups, respectively. CONCLUSIONS: In this post hoc partitioned survival analysis, TFS and TFS without toxicity appeared similar in the IO-TKI group compared with the SUN group. These findings may reflect contin-uation of TKI until progression per protocol design in all trials and discontinuation of IO after 2 years in two trials. See related commentary by Stadler and Karrison, p. 3098.

Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery.

Cepharanthine is a secondary metabolite isolated from Stephania. It has been reported that it has anti-conronaviruses activities including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we assemble three Stephania genomes (S. japonica, S. yunnanensis, and S. cepharantha), propose the cepharanthine biosynthetic pathway, and assess the antiviral potential of compounds involved in the pathway. Among the three genomes, S. japonica has a near telomere-to-telomere assembly with one remaining gap, and S. cepharantha and S. yunnanensis have chromosome-level assemblies. Following by biosynthetic gene mining and metabolomics analysis, we identify seven cepharanthine analogs that have broad-spectrum anti-coronavirus activities, including SARS-CoV-2, Guangxi pangolin-CoV (GX_P2V), swine acute diarrhoea syndrome coronavirus (SADS-CoV), and porcine epidemic diarrhea virus (PEDV). We also show that two other genera, Nelumbo and Thalictrum, can produce cepharanthine analogs, and thus have the potential for antiviral compound discovery. Results generated from this study could accelerate broad-spectrum anti-coronavirus drug discovery.

Carbopol 940-based hydrogels loading synergistic combination of quercetin and luteolin from the herb Euphorbia humifusa to promote Staphylococcus aureus infected wound healing.

With the increasing prevalence of Staphylococcus aureus infections, rapid emergence of drug resistance and the slow healing of infected wounds, developing an efficient antibiotic-free multifunctional wound dressing for inhibiting S. aureus and simultaneously facilitating wound healing have become a huge challenge. Due to their excellent biocompatibility and biodegradability, some carbopol hydrogels based on plant extracts or purified compounds have already been applied in wound healing treatment. In China, Euphorbia humifusa Willd. (EuH) has been traditionally used as a medicine and food homologous medicine for the treatment of furuncles and carbuncles mainly caused by S. aureus infection. In an earlier study, EuH-originated flavonoids quercetin (QU) and luteolin (LU) could serve as a potential source for anti-S. aureus drug discovery when used in synergy. However, the in vivo effects of QU and LU on S. aureus-infected wound healing are still unknown. In this study, we found a series of Carbopol 940-based hydrogels loading QU and LU in combination could disinfect S. aureus and also could promote wound healing. In the full-thickness skin defect mouse model infected with S. aureus, the wound contraction ratio, bacterial burden, skin hyperplasia and inflammation score, as well as collagen deposition and blood vessels were then investigated. The results indicate that the optimized QL2 [QU (32 µg mL-1)-LU (8 µg mL-1)] hydrogel with biocompatibility significantly promoted S. aureus-infected wound healing through anti-infection, anti-inflammation, collagen deposition, and angiogenesis, revealing it as a promising alternative for infected wound repair.

Digitally driven surgical guide planning.

To investigate the role of a fully digital process in the surgical treatment of mandibular fractures in children. We analyzed a complete dataset from 22 children with mandibular fractures treated with digital surgical assistance. The patient's treatment process included preoperative thin layer CT (Computed Tomography) scanning, computer-aided design (3D reconstruction, virtual reduction, and internal fixation device determination and shaping), and 3D printing (jaw model, bite plate). We used occlusal and shaping plates during surgery to assist in fracture reduction and fixation. During the follow-up, we observed the occurrence of fracture healing, occlusal relationships, opening degrees, and complications in pediatric patients after surgery. Next, we used the 3D overlay function of MIMICS software to compare the preoperative surgical design with postoperative jaw imaging data to evaluate the overall surgical effect. The postoperative imaging data showed good fracture healing, normal occlusion during follow-up, and significant improvement in opening degrees. The mean preoperative opening degree was 23.59 ± 2.89 mm, and the mean postoperative opening degree was 29.82 ± 1.79 mm; there was a significant difference between these two parameters (p < 0.05). There were no complications such as tooth germ injury, nerve injury or fracture block displacement. The postoperative mandibular imaging data was imported into MIMICS software for 3D overlay visualization, and the postoperative mandibular morphology recovery was well-matched with the preoperative design. We measured the average upper deviation (0.65 ± 0.09) mm and the average lower deviation (-0.57 ± 0.14) mm. The fully digital process has a precise, minimally invasive, and safe effect in the surgical treatment of mandibular fractures in children, and the clinical effect is satisfactory.