PHGDH/SYK: a hub integrating anti-fungal immunity and serine metabolism.

Immune cells modify their metabolic pathways in response to fungal infections. Nevertheless, the biochemical underpinnings need to be better understood. This study reports that fungal infection drives a switch from glycolysis to the serine synthesis pathway (SSP) and one-carbon metabolism by inducing the interaction of spleen tyrosine kinase (SYK) and phosphoglycerate dehydrogenase (PHGDH). As a result, PHGDH promotes SYK phosphorylation, leading to the recruitment of SYK to C-type lectin receptors (CLRs). The CLR/SYK complex initiates signaling cascades that lead to transcription factor activation and pro-inflammatory cytokine production. SYK activates SSP and one-carbon metabolism by inducing PHGDH activity. Then, one-carbon metabolism supports S-adenosylmethionine and histone H3 lysine 36 trimethylation to drive the production of pro-inflammatory cytokines and chemokines. These findings reveal the crosstalk between amino acid metabolism, epigenetic modification, and CLR signaling during fungal infection.

GmBSK1-GmGSK1-GmBES1.5 regulatory module controls heat tolerance in soybean.

INTRODUCTION: Heat stress poses a severe threat to the growth and production of soybean (Glycine max). Brassinosteroids (BRs) actively participate in plant responses to abiotic stresses, however, the role of BR signaling pathway genes in response to heat stress in soybean remains poorly understood. OBJECTIVES: In this study, we investigate the regulatory mechanisms of GmBSK1 and GmBES1.5 in response to heat stress and the physiological characteristics and yield performance under heat stress conditions. METHODS: Transgenic technology and CRISPR/Cas9 technology were used to generated GmBSK1-OE, GmBES1.5-OE and gmbsk1 transgenic soybean plants, and transcriptome analysis, LUC activity assay and EMSA assay were carried out to elucidate the potential molecular mechanism underlying GmBSK1-GmBES1.5-mediated heat stress tolerance in soybean. RESULTS: CRISPR/Cas9-generated gmbsk1 knockout mutants exhibited increased sensitivity to heat stress due to a reduction in their ability to scavenge reactive oxygen species (ROS). The expression of GmBES1.5 was up-regulated in GmBSK1-OE plants under heat stress conditions, and it directly binds to the E-box motif present in the promoters of abiotic stress-related genes, thereby enhancing heat stress tolerance in soybean plants. Furthermore, we identified an interaction between GmGSK1 and GmBES1.5, while GmGSK1 inhibits the transcriptional activity of GmBES1.5. Interestingly, the interaction between GmBSK1 and GmGSK1 promotes the localization of GmGSK1 to the plasma membrane and releases the transcriptional activity of GmBES1.5. CONCLUSION: Our findings suggest that both GmBSK1 and GmBES1.5 play crucial roles in conferring heat stress tolerance, highlighting a potential strategy for breeding heat-tolerant soybean crops involving the regulatory module consisting of GmBSK1-GmGSK1-GmBES1.5.

Spatial Transcriptomics Reveals the Transcriptomic Signatures in a Mouse Model of Pediatric Metabolic Dysfunction-Associated Steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is considered the progressive form of metabolic dysfunction-associated steatotic liver disease, which is the leading cause of chronic liver disease in children. However, the pathogenesis of pediatric MASH remains poorly understood because of the lack of animal models. In this study, we developed a mouse model of pediatric MASH and characterized the hepatic transcriptomic profile using spatial transcriptomics technology. C57BL/6J mice were fed a Western diet (WD) along with weekly injections of carbon tetrachloride (CCl4) from the age of 3 to 8 weeks. After 5 weeks of feeding, WD + CCl4-treated mice showed significant liver injury without the development of insulin resistance. Histologically, WD + CCl4 induced key features of type 2 MASH, the most common type observed in children, characterized by liver steatosis, portal inflammation, and portal fibrosis. Through spatial transcriptomics analysis of liver tissues, we identified that cluster 0 in the mouse from the WD + CCl4 group was enriched in pathways associated with lipid metabolism. Further investigation revealed that cytochrome p450 2E1 was the top marker gene of cluster 0, and its expression was increased in the periportal area of mice from the WD + CCl4 group. These findings suggest that our mouse model of pediatric MASH mirrors the histologic features of human MASH, and the up-regulation of cytochrome p450 2E1 may be linked to the disease pathogenesis.

The application of lung immune prognostic index in predicting the prognosis of 302 STS patients.

Background: Soft tissue sarcoma (STS) are heterogeneous and rare tumors, and few studies have explored predicting the prognosis of patients with STS. The Lung Immune Prognostic Index (LIPI), calculated based on baseline serum lactate dehydrogenase (LDH) and the derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR), was considered effective in predicting the prognosis of patients with pulmonary cancer and other malignancies. However, the efficacy of the LIPI in predicting the prognosis of patients with STS remains unclear. Methods: This study retrospectively reviewed patients with STS admitted to our center from January 2016 to January 2021. Their hematological and clinical characteristics were collected and analyzed to construct the LIPI specific to STS. The correlations between various predictive factors and overall survival (OS) were examined using Kaplan-Meier and Cox regression analyses. Independent risk factors for OS were identified using univariate and multivariate analyses. Finally, a LIPI nomogram model for STS was established. Results: This study enrolled 302 patients with STS, of which 87 (28.9%), 162 (53.6%), and 53 (17.5%) were classified into three LIPI-based categories: good, moderate, and poor, respectively (P < 0.0001). The time-dependent operator curve showed that the LIPI had better prognostic predictive ability than other hematological and clinical characteristics. Univariate and multivariate analyses identified the Fédération Nationale des Centres de Lutte Contre le Cancer grade (FNCLCC/G), tumor size, and LIPI as independent risk factors. Finally, a nomogram was constructed by integrating the significant prognostic factors. Its C-index was 0.72, and the calibration curve indicated that it could accurately predict the three- and five-year OS of patients with STS. The decision and clinical impact curves also indicated that implementing this LIPI-nomogram could significantly benefit patients with STS. Conclusion: This study explored the efficacy of the LIPI in predicting the prognosis of 302 patients with STS, classifying them into three categories to evaluate the prognosis. It also reconstructed a LIPI-based nomogram to assist clinicians in predicting the three- and five-year OS of patients with STS, potentially enabling timely intervention and customized management.

High expression of ABL2 promotes gastric cancer cells migration, invasion and proliferation via the TGF-ß and YAP signaling pathways.

Background: The Abelson-Related Gene (ABL2) is expressed in various malignancies. However, its role in gastric cancer (GC) regarding tumor proliferation, metastasis, and invasion remains unclear. Methods: ABL2 expression in clinical specimens was assessed using quantitative real-time fluorescence PCR (qRT-PCR). Western blotting and immunofluorescence assay determined protein levels. Additionally, Transwell migration and invasion, cell counting kit-8 (CCK-8) and colony-formation assays analyzed the effect of ABL2 on GC cells. Protein levels related to GC cells were assessed through Western blotting. The effects of si-ABL2 combined with GA-017 that activated YAP on cell migration, invasion and proliferation were investigated. Results: ABL2 expression was upregulated in human GC tissues compared to paracancer tissues, and it was positively related to tumor node metastasis classification (TNM) stage. Furthermore, high ABL2 levels promoted the proliferation, metastasis, and invasion capacity in GC cells. Elevated ABL2 expression enhanced the expression of MMP2, MMP9, and PCNA while decreasing TIMP1 and TIMP2 expression. It also increased the p-SMAD2/3 expression and YAP expression, decreased the expression of p-YAP in GC cells. Furthermore, GA-017 increased ABL2 expression in MGC-803 cells and counteracted the effects of si-ABL2 on cell migration, invasion and proliferation. Conclusion: These findings indicated that heightened ABL2 expression could activate TGF-ß/SMAD2/3 and YAP signaling pathway, promoting epithelial mesenchymal transformation (EMT), and enhancing multiplication, metastasis, and invasion in GC cells.

Effect of high-dose N-acetylcysteine on exacerbations and lung function in patients with mild-to-moderate COPD: a double-blind, parallel group, multicentre randomised clinical trial.

Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio <0.70 and an FEV1 ≥ 50% predicted value after bronchodilator use). The coprimary outcomes were the annual rate of total exacerbations and the between-group difference in the change from baseline to 24 months in FEV1 before bronchodilator use. COPD exacerbation was defined as the appearance or worsening of at least two major symptoms (cough, expectoration, purulent sputum, wheezing, or dyspnoea) persisting for at least 48 hours. Assessment of exacerbations was conducted every three months, and lung function was performed annually after enrolment. The difference between the N-acetylcysteine group and the placebo group in the annual rate of total exacerbation were not significant (0.65 vs. 0.72 per patient-year; relative risk [RR], 0.90; 95% confidence interval [CI], 0.80-1.02; P = 0.10). There was no significant difference in FEV1 before bronchodilator use at 24 months. Long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improved lung function in patients with mild-to-moderate COPD. Chinese Clinical Trial Registration: ChiCTR-IIR-17012604.

A droplet digital PCR assay to detect Chinese rice-field eels rhabdovirus.

Chinese rice-field eels rhabdovirus (CrERV) causes haemorrhagic disease in Chinese rice-field eels (Monopterus albus), leading to significant mortality and economic losses. Sensitive detection of CrERV nucleic acids is essential to control the spread of this pathogen and to treat infected individuals. Herein, we developed an efficient and sensitive droplet digital PCR (ddPCR) method to rapidly detect and quantify CrERV. The ddPCR assay optimal conditions were an annealing temperature of 53°C, and primer and probe concentrations of 0.5 and 0.25 µM, respectively. The assay had a diagnostic sensitivity of 0.23 copies/µL, and was highly specific, showing no cross reactivity with other viruses (infectious haematopoietic necrosis virus, grass carp reovirus, spring viremia of carp virus, largemouth bass ranavirus, carp edema virus, Chinese giant salamander iridovirus, and white spot syndrome virus). Real-time quantitative PCR testing of 30 Chinese rice-field eels samples detected CrERV in 7 samples (23.3%), whereas ddPCR detected CrERV in 12 samples (40%), demonstrating its higher sensitivity. Thus, ddPCR represents an advanced method to absolutely quantify CrERV in infected fish with low virus concentrations, providing a valuable tool to manage the spread and impact of CrERV.

Differentiating calcifications from cerebral microbleeds using quantitative susceptibility mapping.

OBJECTIVES: To differentiate cerebral microbleeds (CMBs) and calcifications using quantitative susceptibility mapping (QSM). METHODS: CMBs were visualized and located using QSM from susceptibility-weighted imaging data collected on a 3-T MR scanner. Calcifications of the pineal gland and the choroid plexus were localized first using CT. All calcifications and CMBs were assessed using QSM to evaluate their magnetic susceptibility. The distribution of the magnetic susceptibility for the CMBs was determined and the CT attenuation was correlated with the mean magnetic susceptibility for the calcifications. RESULTS: A total of 232 hypointense foci were selected from the QSM data: 121 were CMBs and 111 were calcifications. The mean magnetic susceptibility was -214 ± 112 ppb for the calcifications and 392 ± 204 ppb for the CMBs. The minimum value of magnetic susceptibility was 75 ppb for all the CMBs and the maximum value was -52 ppb for all the calcifications. The calcifications were clearly differentiable from the CMBs from the sign alone (p < 0.001). The magnetic susceptibility for the CMBs was 299 ± 133 ppb in the lobar subcortical white matter and 499 ± 220 ppb for deep CMBs in the basal ganglia, thalamus, and brainstem. There was a significant difference in the susceptibility between these two regions (p < 0.001). CONCLUSION: The sign of the magnetic susceptibility was sufficient to differentiate calcifications and CMBs. The concentration of calcium or iron can be determined from the susceptibility value itself. The deep CMBs had higher susceptibility on average than lobar bleeds. CLINICAL RELEVANCE STATEMENT: This study's ability to differentiate between CMBs and calcifications using QSM could enhance diagnostic accuracy, guiding more precise treatment decisions for stroke or tumor patients. KEY POINTS: The sign of magnetic susceptibility is sufficient to differentiate calcifications and CMBs. QSM can successfully differentiate calcifications from microbleeds. The concentration of calcium or iron can be determined from the susceptibility value itself.

Bioinspired triple-layered membranes for periodontal guided bone regeneration applications.

Barrier membranes have been used for the treatment of alveolar bone loss caused by periodontal diseases or trauma. However, an optimal barrier membrane must satisfy multiple requirements simultaneously, which are challenging to combine into a single material. We herein report the design of a bioinspired membrane consisting of three functional layers. The primary layer is composed of clay nanosheets and chitin, which form a nacre-inspired laminated structure. A calcium phosphate mineral layer is deposited on the inner surface of the nacre-inspired layer, while a poly(lactic acid) layer is coated on the outer surface. The composite membrane integrates good mechanical strength and deformability because of the nacre-inspired structure, facilitating operations during the implant surgery. The mineral layer induces the osteogenic differentiation of bone marrow mesenchymal stem cells and increases the stiffness of the membrane, which is an important factor for the regeneration process. The poly(lactic acid) layer can prevent unwanted mineralization on the outer surface of the membrane in oral environments. Cell experiments reveal that the membrane exhibits good biocompatibility and anti-infiltration capability toward connective tissue/epithelium cells. Furthermore, in vitro analyses show that the membrane does not degrade too fast, allowing enough time for bone regeneration. In vivo experiments prove that the membrane can effectively induce better bone regeneration and higher trabecular bone density in alveolar bone defects. This study demonstrates the potential of this bioinspired triple-layered membrane with hierarchical structures as a promising barrier material for periodontal guided tissue regeneration.

Cooperative Diarylborinic Acid/Chloride-Catalyzed Formal SNi Reaction of cis-4-Hydroxymethyl-1,2-Cyclopentene Oxides.

A catalytic formal SNi reaction was designed to achieve stereoretentive products for cis-4-hydroxymethyl-1,2-cyclopentene oxides by using diarylborinic acid as a dual role catalyst and chloride as a catalytic transient nucleophile through a double-displacement mechanism. This reaction offers the advantages of a low catalyst loading of 0.1 mol % and wide substrate scope, even including N-substituents. The use of chiral boron acid as a catalyst for this reaction was also attempted.

Machine learning predicts acute respiratory failure in pancreatitis patients: A retrospective study.

PURPOSE: The purpose of the research is to design an algorithm to predict the occurrence of acute respiratory failure (ARF) in patients with acute pancreatitis (AP). METHODS: We collected data on patients with AP in the Medical Information Mart for Intensive Care IV database. The enrolled observations were randomly divided into a 70 % training cohort and a 30 % validation cohort, and the observations in the training cohort were divided into ARF and non-ARF groups. Feature engineering was conducted using random forest (RF) and least absolute shrinkage and selection operator (LASSO) methods in the training cohort. The model building included logistic regression (LR), decision tree (DT), k-nearest neighbours (KNN), naive bayes (NB) and extreme gradient boosting (XGBoost). Parameters for model evaluation include receiver operating characteristic (ROC) curve, precision-recall curve (PRC), calibration curves, positive predictive value (PPV), negative predictive value (NPV), true positive rate (TPR), true negative rate (TNR), accuracy (ACC) and F1 score. RESULTS: Among 4527 patients, 445 patients (9.8 %) experienced ARF. Ca, ALB, GLR, WBC, AG and BUN have been included in the prediction model as features for predicting ARF. The AUC of XGBoost were 0.86 (95 %CI 0.84-0.88) and 0.87 (95 %CI 0.84-0.90) in the training and validation cohorts. In the training cohort, XGBoost demonstrates a true positive rate (TPR) of 0.662, a true negative rate (TNR) of 0.884, a positive predictive value (PPV) of 0.380, a negative predictive value (NPV) of 0.960, an accuracy (ACC) of 0.862, and an F1 score of 0.483. In the validation cohort, XGBoost shows a TPR of 0.620, a TNR of 0.895, a PPV of 0.399, an NPV of 0.955, an ACC of 0.867, and an F1 score of 0.486. CONCLUSION: The XGBOOST model demonstrates good discriminatory ability, which enables clinicians to ascertain the probability of developing ARF in AP patients.

Modular Hemipelvic Prosthesis Preserves Normal Biomechanics and Showed Good Compatibility: A Finite Element Analysis.

This study aimed to evaluate the biomechanical compatibility of a modular hemipelvic prosthesis by comparing stress distributions between an implanted pelvis and a healthy pelvis. Finite element analysis was used to simulate bilateral standing loads on both models, analyzing critical regions such as the sacroiliac joints, iliac crest, acetabulum, and prosthesis connection points. Six models with varied displacements of the hip joint rotational center were also introduced to assess the impact of deviations on stress distribution. The implanted pelvis had a stress distribution closely matching that of the intact pelvis, indicating that the prosthesis design maintained the biomechanical integrity of the pelvis. Stress patterns in displacement models with deviations of less than 10 mm were similar to the standard model, with only minor changes in stress magnitude. However, backward, upward, and inward deviations resulted in stress concentrations, particularly in the prosthesis connection points, increasing the likelihood of mechanical failure. The modular hemipelvic prosthesis demonstrated good biomechanical compatibility with minimal impact on pelvic stress distribution, even with moderate deviations in the hip joint's rotational center; outward, forward, and downward displacements are preferable to minimize stress concentration and prevent implant failure in cases where minor deviations in the rotational center are unavoidable during surgery.

Gas Sensing Properties of Indium-Oxide-Based Field-Effect Transistor: A Review.

Excellent stability, low cost, high response, and sensitivity of indium oxide (In2O3), a metal oxide semiconductor, have been verified in the field of gas sensing. Conventional In2O3 gas sensors employ simple and easy-to-manufacture resistive components as transducers. However, the swift advancement of the Internet of Things has raised higher requirements for gas sensors based on metal oxides, primarily including lowering operating temperatures, improving selectivity, and realizing integrability. In response to these three main concerns, field-effect transistor (FET) gas sensors have garnered growing interest over the past decade. When compared with other metal oxide semiconductors, In2O3 exhibits greater carrier concentration and mobility. The property is advantageous for manufacturing FETs with exceptional electrical performance, provided that the off-state current is controlled at a sufficiently low level. This review presents the significant progress made in In2O3 FET gas sensors during the last ten years, covering typical device designs, gas sensing performance indicators, optimization techniques, and strategies for the future development based on In2O3 FET gas sensors.

MEOX1 triggers myofibroblast apoptosis resistance, contributing to pulmonary fibrosis in mice.

The apoptosis resistance of myofibroblasts is a hallmark in the irreversible progression of pulmonary fibrosis (PF). While the underlying molecular mechanism remains elusive. In this study, we unveiled a previously unrecognized mechanism underlying myofibroblast apoptosis resistance during PF. Our investigation revealed heightened expression of mesenchyme homeobox 1 (MEOX1) in the lungs of idiopathic pulmonary fibrosis (IPF) patients and bleomycin-induced PF mice. Silencing MEOX1 significantly attenuated PF progression in mice. In vitro, we found a notable increase in MEOX1 expression in transforming growth factor-ß1 (TGF-ß1)-induced myofibroblasts. Silencing MEOX1 enhanced apoptosis of myofibroblasts. Mechanistically, we identified G-protein signaling pathway regulatory factor 4 (RGS4) as a critical downstream target of MEOX1, as predicted by bioinformatics analysis. MEOX1 enhanced apoptosis resistance by upregulating RGS4 expression in myofibroblasts. In conclusion, our study highlights MEOX1 as a promising therapeutic target for protecting against PF by modulating myofibroblast apoptosis resistance.

Short-to-Mid-Term Outcomes of Ipsilateral Femoral Head Autograft Combined with Uncemented Total Hip Replacement for Partial Periacetabular Defects Following Tumor Resection.

OBJECTIVE: Periacetabular tumors, especially in young to middle-aged patients with invasive benign tumors or low-grade malignant tumors involving type II or II + III, present significant challenges due to their rarity and the complexity of the anatomical and biomechanical structures involved. The primary difficulty lies in balancing the need to avoid unfavorable oncological outcomes while maintaining postoperative hip joint function during surgical resection. This study aimed to evaluate the effectiveness and reliability of a surgical method involving partial weight-bearing acetabular preservation combined with the use of an uncontaminated femoral head autograft to reconstruct the segmental bone defect after intra-articular resection of the tumorous joint, providing a solution that ensures both oncological safety and functional preservation of the hip joint in these patients. METHODS: We conducted a retrospective study with a follow-up period of at least 36 months. From January 2010 to October 2020, we reviewed 20 cases of patients under 60 year of age with periacetabular invasive benign tumors or primary low-grade malignant tumors. All patients underwent reconstruction of the tumorous joint using autologous femoral head grafts. Data collected included patient age, gender, tumor type, preoperative and postoperative visual analog scale (VAS) scores, Musculoskeletal Tumor Society (MSTS) scores, Harris Hip Scores (HHS), patient survival rates, postoperative tumor recurrence, and surgical complications. To analyze the data, we utilized various statistical methods, including descriptive statistics to summarize patient demographics and clinical characteristics, and paired sample t-tests to compare preoperative and postoperative scores. RESULTS: The study included 20 patients, and a total median follow-up was 83 months. Their pathologic diagnoses comprised 13 giant cell tumors (GCTs), 5 chondrosarcomas, one chondroblastoma, and 1 leiomyosarcoma. Postoperatively, the median differences in vertical and horizontal center of rotation (COR) were 3.8 and 4.0 mm. Median limb length discrepancy (LLD) postoperatively was 5.7 mm (range, 2.3-17.8 mm). Two patients (10%) experienced delayed wound healing, resolved with antibiotics and early surgical debridement. One patient experienced dislocation 3 months postoperatively, which was promptly addressed under general anesthesia without further dislocation. CONCLUSION: Through multiplanar osteotomy with limited margins, femoral head autograft, and uncemented total hip replacement for pelvic segmental bone defects in selected patients in type II or II + III appears to be an encouraging limb-sparing surgery worthy of consideration for carefully selected patients.

Rationally designed hierarchical hollow CuS/CdIn2S4 heterostructure nanoboxes for boosted photoreduction of CO2.

A novel double-shelled CuS/CdIn2S4 photocatalyst was rationally designed using CdIn2S4 sheets in situ grown upon the exterior of hollow CuS nanocubes. The unique hierarchical hollow structure of CuS/CdIn2S4 provides numerous active sites and reduces carrier diffusion length. Surface sulfur vacancies mitigate the detachment of the intermediate, which is favorable for a multi-electron reaction path such as that in the production of CH4. Meanwhile, a suitable band-structure alignment between p-type CuS and n-type CdIn2S4 leads to the formation of a type-II heterostructure, thus resulting in effective light-harvesting and spatial separation of electron-hole pairs for CO2 photoreduction. The CuS/CdIn2S4 heterostructure exhibits significantly enhanced performance with a boosted CO yield of 40.73 µmol g-1 h-1 as well as a noticeably improved CH4 selectivity (36.5%, 23.41 µmol g-1 h-1). This work introduces innovative concepts in designing photocatalytic systems with unique morphologies and rational band structures, promising advancements in CO2 photoreduction at reduced costs.

Restoration of ARA metabolic disorders in vascular smooth muscle cells alleviates intimal hyperplasia.

Intimal hyperplasia (IH) is an innegligible issue for patients undergoing interventional therapy. The proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor-BB (PDGF-BB) are critical events in the development of IH. While the exact mechanism and effective target for IH needs further investigation. Metabolic disorders of arachidonic acid (ARA) are involved in the occurrence and progression of various diseases. In this study, we found that the expressions of soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) were significantly increased in the VSMCs during balloon injury-induced IH. Then, we employed a COX-2/sEH dual inhibitor PTUPB to increase the concentration of epoxyeicosatrienoic acids (EETs) while prevent the release of pro-inflammatory prostaglandins. Results showed that PTUPB treatment significantly reduced neointimal thickening induced by balloon injury in rats in vivo and inhibited PDGF-BB-induced proliferation and migration of VSMCs in vitro. Our results showed that PTUPB may reverse the phenotypic transition of VSMCs by inhibiting Pttg1 expression. In conclusion, we found that the dysfunction of ARA metabolism in VSMCs contributes to IH, and the COX-2/sEH dual inhibitor PTUPB attenuates IH progression by reversing the phenotypic switch in VSMC through the Sirt1/Pttg1 pathway.

Case report: Individualized 3D-printed uncemented distal fibular prosthesis preserving the lateral malleolus for repair of distal fibular defects.

Background: Involvement of the distal fibula by alveolar soft-part sarcoma is rare. Extensive resection or amputation may be needed; however, distal fibula resection can disrupt foot and ankle biomechanics, leading to ankle joint instability. Reports on joint preservation for maintaining optimal ankle joint function are scarce. Computer-aided design and individualized three-dimensional (3D)-printed uncemented implants represent an evolving solution for reconstructing the distal fibula. Case presentation: A 34-year-old woman was diagnosed with alveolar soft-part sarcoma in the right lower leg involving the cortical bone of the fibula. After anlotinib treatment, the tumor size decreased, and the tumor response rate was a partial response (PR); however, the patient continued to experience adverse reactions. With multiple disciplinary team discussions, surgical resection was deemed appropriate. Due to the extensive defect and ankle joint instability after resection, a custom-made 3D-printed prosthesis was designed and fabricated to reconstruct the defect, preserving the lateral malleolus. During the follow-up, the patient achieved favorable ankle function, and no prosthesis-related complications were observed. Conclusion: 3D-printed personalized uncemented implants constitute a novel approach and method for addressing the reconstruction issues of the distal fibula and ankle joint. Through the personalized design of 3D-printed prostheses, the lateral malleolus can be preserved, ensuring the normal anatomical structure of the ankle joint. They achieve a well-integrated interface between the prosthesis and bone, ensuring satisfactory postoperative function. Additionally, they offer valuable insights for reconstructing distal bone defects near joints in the extremities. However, confirming these findings requires extensive cohort studies.