Oxygen-Evolving Radiotherapy-Radiodynamic Therapy Synergized with NO Gas Therapy by Cerium-Based Rare-Earth Metal-Porphyrin Framework.

The efficacy of traditional radiotherapy (RT) has been severely limited by its significant side effects, as well as tumor hypoxia. Here, the nanoscale cerium (Ce)-based metaloxo clusters (Ce(IV)6)-porphyrin (meso-tetra (4-carboxyphenyl) porphyrin, TCPP) framework loaded with L-arginine (LA) (denoted as LA@Ce(IV)6-TCPP) is developed to serve as a multifarious radio enhancer to heighten X-ray absorption and energy transfer accompanied by O2/NO generation for hypoxia-improved RT-radiodynamic therapy (RDT) and gas therapy. Within tumor cells, LA@Ce(IV)6-TCPP will first react with endogenous H2O2 and inducible NO synthase (iNOS) to produce O2 and NO to respectively increase the oxygen supply and reduce oxygen consumption, thus alleviating tumor hypoxia. Then upon X-ray irradiation, LA@Ce(IV)6-TCPP can significantly enhance hydroxyl radical (•OH) generation from Ce(IV)6 metaloxo clusters for RT and synchronously facilitate singlet oxygen (1O2) generation from adjacently-coordinated TCPP for RDT. Moreover, both the •OH and 1O2 can further react with NO to generate more toxic peroxynitrite anions (ONOO-) to inhibit tumor growth for gas therapy. Benefitting from the alleviation of tumor hypoxia and intensified RT-RDT synergized with gas therapy, LA@Ce(IV)6-TCPP elicited superior anticancer outcomes. This work provides an effective RT strategy by using low doses of X-rays to intensify tumor suppression yet reduce systemic toxicity.

Ultrasonic Evaluation of the Asian Nasal Soft Tissue Envelope.

OBJECTIVE: The thickness of the nasal soft tissue envelope (STE) plays a crucial role in the final rhinoplasty results. The Asian nasal contour is typically characterized by a thicker STE and broader nasal tip, but objective data are lacking. The purpose of this study was to objectively measure nasal dermal thickness and overall STE thickness and to determine any demographic differences. METHODS: From July to September 2023, 110 patients presenting for consultation underwent ultrasound evaluation of their nasal STE. STE thickness was measured at predetermined subsites and compared with published data on white patients. RESULTS: The thickness of the STE in Asian patients was greater than that in white patients. The STE was thickest at the supratip (mean [SD]), (4.88 [0.74] mm) rather than at the nasion and thinnest at the rhinion (2.25 [0.51] mm). The nasal tip (4.07 [0.72] mm) showed comparable STE thickness with the nasion (4.13 [0.72] mm) but had a significantly thicker dermis than the nasion (2.35 ± 0.49 mm vs. 1.35 ± 0.35 mm, P < 0.05). Male sex and higher BMI tended to be correlated with a thicker nasal STE, but age did not show any relationship. A thicker nasal tip STE showed significantly greater nasal tip width and nasal alar thickness. CONCLUSION: STE thickness at different nasal subsites varies and affects external nasal contour and rhinoplasty outcomes. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Clinical efficacy of blood derivatives on wound healing: A systematic review and network meta-analysis.

This study aims to evaluate the clinical effects of different blood derivatives on wound healing using network meta-analysis. PubMed, Embase, OVID, Web of Science, SCOPUS and Cochrane Central were searched to obtain studies about blood derivatives on wound healing until October 2023. R 4.2.0 and Stata 15.0 softwares were used for data analysis. Forty-four studies comprising 5164 patients were included. The results of network meta-analysis showed that the healing area from high to low was GF + ORCCB, ORCCB, GF, PRF, Unnas paste dressing, APG, PRP injection, PRP, PRP + thrombin gel, PPP, HPL, CT. The healing time from low to high was PRP + thrombin gel, GF, PRP, PC + K, PC, APG, PRF, CT, Silver sulfadiazine ointment. The number of patients cured from high to low was APG, PRP injection, PRP, Aurix, PRF, Leucopatch, HPL, Antimicrobial Ointment Dressing, CT, 60 µg/cm2 repifermin, 120 µg/cm2 repifermin, AFG, PPP. The order of analgesic effect from high to low was AFG, Aminogam gel, PRF, PRP, Oxidised oil, APG, GF, CT. The order of the number of wound infection cases from low to high is APG, 20 µg/cm2 repifermin, 60 µg/cm2 repifermin, PRP, LeucoPatch, CT, PPP, Antiseptic ointment dressing. Healing area: GF + ORCCB had the best effect; Healing time: PRP + thrombin gel took the shortest time. The number of cured patients and the reduction of wound infection: APG has the best effect. Analgesic effect: AFG has the best effect. More studies with large sample sizes are needed to confirm the above findings.

Assessing the effectiveness of filtration + UV-C radiation for the treatment of simulated ballast water at various holding times.

In recent years, the issue of invasive alien species brought on by ballast water has drawn increasing attention, and advances in ballast water treatment technologies have been made. One of the most popular combined ballast water treatment technologies utilized in ballast water management systems (BWMSs) globally is filtration + UV-C radiation. During the actual voyage of the ship, ballast water is treated by the BWMS and then enters the dark ballast tanks until the ballast water is discharged. Marine organisms are able to complete DNA damage caused by UV radiation in dark ballast tanks. Therefore, the length of holding time affects the effectiveness of the BWMS in treating ballast water. The objective of this study was to examine the efficacy of filtration + UV-C irradiation treatment at different holding times for the removal or inactivation of phytoplankton and zooplankton populations during simulated ballast water treatment. Results indicate that the holding time after the filtration + UV-C radiation treatment increased the inactivating efficacy, especially for zooplankton in natural seawater. For phytoplanktons in ballast water, the strongest impact on the treatment efficacy was reached with a holding time of 24 h.

Phosphoproteome and Biological Evidence Revealed Abnormal Calcium Homeostasis in Keloid Fibroblasts and Induction of Aberrant Platelet Aggregation.

Keloid is a benign tumor characterized by persistent inflammation, increased fibroblast proliferation, and abnormal deposition of collagen in the wound. The etiology of keloid is unclear. Here, we explored the phospho-signaling changes in human keloid fibroblasts via phosphoproteome mass spectrometry analysis. We found that comparative phosphoproteomics could statistically distinguish keloid from control fibroblasts. Differentially expressed phosphoproteins could predict the activation of known keloid-relevant upstream regulators including transforming growth factor-ß1, interleukin (IL)-4, and IL-5. With multiple bioinformatics analyses, phosphorylated FLNA, TLN1, and VCL were significantly enriched in terms of calcium homeostasis and platelet aggregation. We biologically verified that keloid fibroblasts had a higher level of Ca2+ influx than the control fibroblasts upon ionomycin stimulation. Via co-cultivation analysis, we found that human keloid fibroblasts could directly promote platelet aggregation. As suggested by PhosphoPath and gene set enrichment analysis, pFLNA was centered as the top phosphoproteins associated with keloid phenotypes. We validated that pFLNA was upregulated both in keloid fibroblasts and keloid tissue section, implicating its biomarker potential. In conclusion, we reported the first phosphoproteome on keloid fibroblasts, based on which we revealed that keloid fibroblasts had aberrant calcium homeostasis and could directly induce platelet aggregation.

Achieving High Efficiency at High Luminance in Fluorescent Organic Light-Emitting Diodes through Triplet-Triplet Fusion Based on Phenanthroimidazole-Benzothiadiazole Derivatives.

Achieving high efficiency at high luminance is one of the most important prerequisites towards practical application of any kind of light-emitting diode (LED). Herein, we report highly emissive organic fluorescent molecules based on phenanthroimidazole-benzothiadiazole derivatives capable of maintaining high external quantum efficiency (EQE) at high luminance enabled by triplet-triplet fusion (TTF) in doped organic LEDs. The PIBzP-, PIBzPCN-, and PIBzTPA-based devices showed EQEs of 8.27, 9.15, and 8.64 %, respectively, at luminance of higher than 1000 cd m-2 , with little efficiency roll-off.

One step extraction followed by HPLC-ESI-MS/MS for multi-residue analysis of diacylhydrazine insecticides in water, sediment, and aquatic products.

A multi-residue analysis of six diacylhydrazine insecticides in water, sediment, and aquatic products was established by liquid chromatography triple quadrupole tandem mass spectrometry (LC-MS/MS). The water sample was extracted with acetonitrile by low-temperature enrichment liquid-liquid extraction technology. The sediment and aquatic products were prepared using QuEChERS technique. Method validation showed perfect linearity with correlation coefficients (R) more than 0.9992 for all insecticides, and the matrix effects were nearly negligible (-1.42% to -0.27%) for water, sediment and aquatic products. The recoveries were 80.0-99.7% at three spiked levels (0.02 ng·mL-1, 0.1 ng·mL-1, 0.5 ng·mL-1; 2.0, 10, and 50 ng·g-1) and the precisions (intra-day and inter-day precision) were lower than 5.28%, with the low LODs (3.8 ~ 9.6 pg·mL-1; 0.38-0.96 ng·g-1) and LOQs (12.7 ~ 32.0 pg·mL-1; 1.27-3.20 ng·g-1) for water, sediment, and aquatic products, indicating the good accuracy and precision of the proposed method. The applicability, efficiency, and sensitivity of this method have been proved in the analysis of six diacylhydrazine insecticides in water, sediment, and crucian carp in Rice- crucian carp - integrated planting system.

Fat Repositioning With a Combination of Internal Fixation and External Fixation in Transconjunctival Lower Blepharoplasty.

BACKGROUND: Various methods on transconjunctival fat repositioning have been promoted to treat tear trough deformities in patients with eye bags. OBJECTIVES: The authors present a modified approach based on the facial soft-tissue spaces with the combined fixation method. METHODS: A total 226 patients underwent this procedure. Through a preseptal approach, the premaxillary and prezygomatic spaces were sequentially separated. Orbital fat was repositioned into the spaces together with the septum. The proximal part of the septum-fat flap was sutured to orbital rim with internal fixation, and their distal stumps were fixed to the end of the soft spaces with externalized percutaneous sutures. Surgical outcome was assessed by surgeons based on Hirmand's grading system. Patients' satisfaction and quality of life were measured using FACE-Q scales. Magnetic resonance imaging was employed to assess the long-term fate of the transposed fat. RESULTS: Tear trough deformities were eliminated in 86.7% of cases. Scores of lower eyelid FACE-Q decreased significantly (P < 0.05). Patients demonstrated enhanced social confidence (P < 0.05) and high satisfaction (74.3 ± 17.2) and were satisfied with their decision to undergo blepharoplasty (78.2 ± 18.7). Undercorrection occurred in 1 patient. Additional complications included transient granulomas, dye eye, unexplained swelling, and numbness, which resolved in all patients. Magnetic resonance imaging confirmed viability of the transposed fat within 6 to 8 months follow-up. CONCLUSIONS: Transconjunctival fat repositioning, utilizing a combination of internal fixation and external fixation, is an effective approach to treat eye bags and tear trough deformities with good patient and surgeon satisfaction.

Negative Pressure Wound Therapy With Chymotrypsin Irrigation: A Maximal Implant Retention Procedure Treating the Exposure/Infection of Titanium Mesh in Cranioplasty.

This preliminary study aims to investigate the effects of a maximal implant retention procedure. The authors retrospectively reviewed the use of negative pressure wound therapy with chymotrypsin irrigation treating implant infection/exposure in titanium mesh cranioplasty by comparing patients with titanium mesh totally retained, partially removed, or totally removed according to the evaluation during the surgery. Negative pressure wound therapy with chymotrypsin irrigation was applied 5 days after the surgery. The negative pressure was set at -125 to -150 mmHg. A total of 21 patients were included, 4 patients treated with titanium mesh totally removed; 3 patients treated with titanium mesh partially removed; and 14 patients treated with U-shape debridement with titanium mesh preserved completely. However, 1 patient in the U-shape group required a second debridement to remove all implant. Negative pressure wound therapy with chymotrypsin irrigation is a novel procedure and could be used to treat implant-related infection without the exchange of implant.

Death Caused by Vaginal Injection of Hyaluronic Acid and Collagen: A Case Report.

With the expanding utilization of hyaluronic acid (HA) and collagen as cosmetic fillers in plastic and reconstructive surgery, complications due to their excessive use and/or irregular procedures warrant great caution. Recently, a fatal case occurred caused by a poorly regulated procedure of vaginal injection of HA and collagen. A 33-year-old female was admitted to the emergency department 3 hours after the operation with a chief complaint of dyspnea, which initiated 5 to 10 minutes after the operation. Her blood pressure remained low while dopamine pressor and fluid replacement were used. Computed tomography of the chest showed local exudation in the lower lobe of the left lung, enlargement of right atrium and ventricle, and uneven development of the bilateral inferior lobar artery with filling defects. Pulmonary computed tomography angiography and three-dimensional reconstruction showed continuous interruption of pulmonary artery branches of the posterior basal segment of the right lower lobe. Unfortunately, the clinical symptoms caused by vaginal injection aggravated rapidly and could not be effectively controlled. The patient died 9 hours after injection. Pulmonary complications after injection of cosmetic fillers are scarcely reported. Thus far, only 2 cases of HA-related pulmonary complications after vaginal injection have been described. The present case emphasizes that surgeons and other healthcare providers must be aware of the risk of serious pulmonary complications and even death associated with these 2 widely utilized injectable fillers. Level of Evidence: 5.

Effect of the vascularized bone components on the survival of vascularized composite allografts.

BACKGROUND: Vascularized composite allograft (VCA), such as hand and face allograft, contains a vascularized bone component that may provide an immunologic benefit and induce tolerance for the simultaneous inclusion of marrow cells and a marrow microenvironment. We developed a chimeric groin cutaneous/femur flap to investigate the effect of vascularized bone marrow on VCA survival and its ability to induce chimerism. METHODS: Brown Norway and Lewis rats were used as donors and recipients, respectively. The experimental groups were as follows: groin flap transplantation alone, flap plus intravenous donor bone marrow cells and flap plus simultaneous femur transplantation. Animals received a nonmyeloablative conditioning regimen that consisted of 7-Gy thymic irradiation, 0.75-mL antilymphocyte serum, and 8-mg-1kg-1d cyclosporine A. The flap survival time, peripheral blood chimerism, and the bone marrow of transplanted femurs were analyzed and compared between groups. RESULTS: Our data showed that the conditioning regimen was effective in T cell ablation. Simultaneous femur transplantation significantly prolonged the median flap survival time (78.8 ± 13.0 d, n = 8) compared with the intravenous bone marrow infusion group (60.9 ± 2.2 d, n = 7) and the control group (58.6 ± 1.3 d, n = 5). Peripheral blood chimerism of 5.81% ± 1.98% was persistently detected for 60 d in recipients of femur transplants but not in the other two groups. Viable bone marrow was confirmed within the transplanted femur on postoperative d 60, but it was gradually replaced by recipient origin cells and eventually developed rejection and fibrosis. CONCLUSIONS: Vascularized bone component plays some protective roles on VCA survival but fails to provide a continuous source of donor cells.

The use of fabricated chimeric flap for reconstruction of extensive foot defects.

Repair of extensive foot defects requires both adequate tissues for wound coverage and special tissues for functional reconstruction. To maximize its function reconstruction, fabricated chimeric flaps consisting of multiple separate flaps were designed to reconstruct such defects. Five patients suffered extensive foot defects with sizes ranging from 23 × 12 cm to 38 × 14 cm(2) in multiple regions including heel, forefoot, dorsum, ankle, anterior leg, and even toes. Causes included crushing injuries, avulsion injuries, and scar excision. Most areas of the defects except heel were first covered by latissimus dorsi muscle flap or anterolateral thigh flap and their pedicles were anastomosed with recipient vessels. Then free medial plantar flaps were transferred for heel reconstruction and their pedicles were further attached to either side branches of the main source vessel or to its distal continuation. All chimeric flaps survived uneventfully and all patients were able to walk in normal footwear during the 1.5- to 4-years follow-up. None of the flaps developed ulcer and flap breakdown. The assessment by Maryland Foot Score showed that four of the five patients gained a "good" recovery and one patient showed moderate improvement of foot functions. Appearances of reconstructed heels were near-normal. The results indicate that fabricated chimeric flap has good design flexibility and may provide an option for functional reconstruction of extensive foot defects. © 2015 Wiley Periodicals, Inc. Microsurgery 36:303-309, 2016.

Reconstruction of Complex Defects of Lower Extremities Using Thinned Free Muscle Flaps.

BACKGROUND: Bulky appearance is a major shortcoming after surface coverage using free muscle flaps. The one-stage thinning procedure at the time of transfer can improve the appearance and avoid additional debulking surgery. We present our experiences in the reconstruction of complex lower extremity defects using thinned free muscle flaps. METHODS: Latissimus dorsi muscle flaps (LDMs) and rectus abdominis muscle flaps (RAMs), which have vessel pedicles running deep in the muscles, were raised and the superficial tissue layers were removed to thin the flaps. These thinned muscle flaps were then used to resurface the wounds on lower extremities followed by coverage of skin autografts on the muscle surfaces. RESULTS: Fourteen LDMs and four RAMs were thinned used for resurfacing eight, five, and three defects on feet, ankles, and pretibial regions, respectively, with wounds that ranged from 6 × 4 cm(2) to 23 × 9 cm(2). All muscle flaps survived the tangential thinning procedures uneventfully. High take rates were observed for most skin grafts, except that a partial skin loss was found in one case. During the 1-20 months follow-up, the skin surface contours over the thinned muscle flaps matched well with adjacent areas. CONCLUSIONS: Intraoperative immediate thinning of LDMs and RAMs can be safely accomplished during the primary reconstruction procedure and may provide an alternative for coverage of complex lower extremity defects. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Intra-Bone Marrow Transplantation of Endosteal Bone Marrow Cells Facilitates Allogeneic Hematopoietic and Stromal Cells Engraftment Dependent on Early Expression of CXCL-12.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) has been considered as an effective approach at inducing allogeneic hematopoietic reconstitution and immune tolerance. However, it remains critical to find the optimal HSCT delivery method and robust sources of hematopoietic stem cells (HSCs). MATERIAL AND METHODS: We introduced a new method by infusing allogeneic endosteal bone marrow cells (BMCs) harvested from long bones endosteum through intra-bone marrow transplantation (IBBMT) into irradiated mice. Recipient mice that were transplanted with central BMCs or through intravenous bone marrow transplantation (IVBMT) were used as controls (n=6 per group). We compared the new method with each control group for allogeneic HSCs homing pattern, peripheral blood chimerism level, skin allograft survival time, and donor stromal cell percentage in recipient BM. AMD3100 was injected to determine whether chemokine stromal cell-derived factor-1 (CXCL-12) was critical for the new method. RESULTS: More allogeneic HSCs homed into spleen and bone marrow for the new method as compared to each control group. IBBMT of endosteal BMCs led to a higher peripheral blood chimerism and skin allograft survival. At 18 weeks, donor stromal cell percentage in recipient BMCs was higher for the new method than in each control group. By AMD3100 blockade at day 1, peripheral blood chimerism level and donor stromal cell percentage were significantly reduced as compared to the control group without AMD3100 blockade. CONCLUSIONS: Our study suggests that IBBMT of endosteal BMCs is an effective approach for HSCT in inducing allogeneic hematopoietic reconstitution. The advantage is dependent upon the early expression of CXCL-12 after bone marrow transplantation.

An alternative model of vascularized bone marrow transplant: partial femur transplantation.

The vascularized whole femur transplantation model is one of the commonly used vascularized bone marrow transplant models. It involves technical complexity and morbidities. To optimize this model, we took 2/3 femur as the carrier of bone marrow cells, and developed a vascularized partial femur model. Four experimental groups were carried out, namely, the syngeneic partial femur transplantation, allogeneic partial femur transplantation with or without cyclosporine A, and allogeneic whole femur transplantation with cyclosporine A. The results showed that the partial femur model was technically simpler and shortened the operative and ischemia time compared to the whole femur model. Gross and histologic appearance confirmed the viability of femur, and its bone marrow inside the bone could also maintain normal morphologically at 60-day posttransplant. Besides, donor multilineage chimerism could be continuously detected in immunosuppressed allogeneic partial femur recipients at 1-, 2-, 3-, 4-, and 8-week posttransplant, and it showed no significant differences when compared with whole femur transplantation. Meanwhile, long-term engraftment of donor-origin cells was also confirmed in recipients' bone marrow, lymph nodes, and spleen, but not in thymus. Therefore, the vascularized partial femur can serve as a continuous resource of bone morrow cells and may provide a useful tool for the study of immune tolerance in vascularized composite allotransplantation.

VDRA downregulate ß-catenin/Smad3 and DNA damage and repair associated with improved prognosis in ccRCC patients.

The clear cell renal cell carcinoma (ccRCC) spotlighted the poorest survival, while chromophobe renal cell carcinoma (chRCC) was associated with the best survival. Earlier studies corroborated vitamin D receptor (VDR) was a promising molecular for improving the prognosis of RCC. In contrast to VDRA, the one of VDR isoforms, VDRB1 (VDR isoform B1) has an N-terminal extension of 50 amino acids and is less ligand-dependent. However, the functional differences between VDRA and VDRB1, and their roles in the prognosis of ccRCC and chRCC, have not been investigated. In the present study, we uncovered that the transcripts related to vitamin D pathway and cellular calcium signaling were effectively decreased in the context of ccRCC, yet failed to exert a comparable effect within chRCC. Specially, minimally levels of VDRA wherein kidneys of patients suffering from ccRCC predict shorter survival time. In addition, the protein expressions for ß-catenin/Smad3 pathway and DNA damage and repair pathways were obviously impeded in VDRA-overexpressed ccRCC cells, yet this inhibitory effect was conspicuously absent in enable VDRB1 cells. Our results provide a new idea to improve the prognosis of ccRCC via VDRA upregulation.

Immunosuppressive Microenvironment in H3K27 Mutant Pediatric Diffuse Midline Glioma: Single-Cell and Bioinformatics Insights on CD8A, IL7R, and ICAM1.

BACKGROUND: Diffuse midline gliomas (DMG) pose a grave threat as a malignant tumor primarily affecting children in the pons region. These tumors exhibit a distinct and heightened resistance to therapeutic interventions, coupled with exceptionally aggressive behavior. METHODS: In this study, we accessed DMG data from the Gene Expression Omnibus (GEO) database. Subsequently, we performed functional annotation and conducted pathway enrichment analysis as well as gene set enrichment analysis (GSEA). Constructing a protein-protein interaction (PPI) network, we identified pivotal hub genes. To evaluate the impact of these hub genes on immune infiltration, we employed the CIBERSORT algorithm. Furthermore, to bolster our findings, we conducted a single-cell analysis. RESULTS: Our findings indicate the involvement of CD8A, IL7R, and ICAM1 in immune responses targeting diverse immune cell types, such as T cells, neutrophils, NK cells, dendritic cells, γδ T cells, and Macrophages M1. Additionally, the presence of immune checkpoints, including IDO1 and TIGIT, likely contributes to intratumoral immunosuppression, thereby fostering the development of an aggressive phenotype and resistance in pediatric DMG. CONCLUSION: In conclusion, the collective findings of our study suggest the potential role of CD8A, IL7R, and ICAM1 as innovative biomarkers for diagnosing and prognosticating pediatric DMG. Moreover, these molecules hold promise as therapeutic targets in the management of this disease. The implications of our research underscore the importance of exploring these novel avenues for improved patient outcomes.

Human serum albumin as the carrier to fabricate STING-activating peptide nanovaccine for antitumor immunotherapy.

Tumor vaccines are emerging as one of the most promising therapeutic strategies for cancer treatment. With the advantages of low toxicity, convenient production and stable quality control, peptide vaccines have been widely used in preclinical and clinical trials involving various malignancies. However, when used alone, they still suffer from significant challenges including poor stability and immunogenicity as well as the low delivery efficiency, leading to limited therapeutic success. Herein, the STING-activating peptide nanovaccine based on human serum albumin (HSA) and biodegradable MnO2 was constructed, which can improve the stability and immunogenicity of antigenic peptides as well as facilitate their uptake by dendritic cells (DCs). Meanwhile, Mn2+ degraded from the nanovaccine can activate the STING pathway and further promote DCs maturation. In this way, the prepared nanovaccine can efficiently mediate T-cell immune responses, thereby exerting the effects of tumor prevention and therapy. Moreover, the prepared nanovaccine possesses the advantages of low cost, convenient preparation and good biocompatibility, showing great potential for practical applications.

Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning.

BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) are important prognostic factors for gastric cancer (GC) that indicate an increased risk of metastasis and poor outcomes. Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment decisions. However, prior models using conventional computed tomography (CT) images to predict LVI or PNI separately have had limited accuracy. Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion. We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients. AIM: To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately. METHODS: This study used a retrospective dataset involving 257 GC patients (training cohort, n = 172; validation cohort, n = 85). First, several clinical indicators, including serum tumor markers, CT-TN stages and CT-detected extramural vein invasion (CT-EMVI), were extracted, as were quantitative spectral CT parameters from the delineated tumor regions. Next, a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters. A logistic regression (LR)-based nomogram model was subsequently constructed to predict LVI/PNI status, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: In both the training and validation cohorts, CT T3-4 stage, CT-N positive status, and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant (P < 0.05). LR analysis of the training group showed preoperative CT-T stage, CT-EMVI, single-energy CT values of 70 keV of venous phase (VP-70 keV), and the ratio of standardized iodine concentration of equilibrium phase (EP-NIC) were independent influencing factors. The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824, respectively, which were slightly greater than those of CT-T and CT-EMVI (AUC = 0.793, 0.762). The nomogram combining CT-T stage, CT-EMVI, VP-70 keV and EP-NIC yielded AUCs of 0.918 (0.866-0.954) and 0.874 (0.784-0.936) in the training and validation cohorts, which are significantly higher than using each of single independent factors (P < 0.05). CONCLUSION: The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC, with accuracy boosted by integrating clinical markers.

FOXP4 is a Direct YAP1 Target that Promotes Gastric Cancer Stemness and Drives Metastasis.

The Hippo-YAP1 pathway is an evolutionally conserved signaling cascade that controls organ size and tissue regeneration. Dysregulation of Hippo-YAP1 signaling promotes initiation and progression of several types of cancer, including gastric cancer (GC). As the Hippo-YAP1 pathway regulates expression of thousands of genes, it is important to establish which target genes contribute to the oncogenic program driven by YAP1 to identify strategies to circumvent it. Here, we identified a vital role of FOXP4 in YAP1-driven gastric carcinogenesis by maintaining stemness and promoting peritoneal metastasis. Loss of FOXP4 impaired GC spheroid formation and reduced stemness marker expression, while FOXP4 upregulation potentiated cancer cell stemness. RNA-seq analysis revealed SOX12 as downstream target of FOXP4, and functional studies established that SOX12 supports stemness in YAP1-induced carcinogenesis. A small molecule screen identified 42-(2-Tetrazolyl)rapamycin as a FOXP4 inhibitor, and targeting FOXP4 suppressed GC tumor growth and enhanced the efficacy of 5-FU chemotherapy in vivo. Collectively, these findings revealed that FOXP4 upregulation by YAP1 in GC regulates stemness and tumorigenesis by upregulating SOX12. Targeting the YAP1-FOXP4-SOX12 axis represents a potential therapeutic strategy for GC.