Neoadjuvant targeted immunotherapy followed by surgical resection versus upfront surgery for hepatocellular carcinoma with macrovascular invasion: A multicenter study.

Background: This study aimed to investigate the safety and efficacy of preoperative targeted immunotherapy followed by surgical resection for hepatocellular carcinoma (HCC) patients with macrovascular invasion. Method: Clinical information of HCC patients with macrovascular invasion was collected from four medical centers. These patients were divided into two cohorts: the upfront surgery group (n=40) and the neoadjuvant group (n=22). Comparisons between the two groups were made with appropriate statistical methods. Results: HCC Patients with macrovascular invasion in the neoadjuvant group were associated with increased incidence of postoperative ascites (72.73% vs. 37.5%, P=0.008), but shorter postoperative hospital stay (10 days vs. 14 days, P=0.032). Furthermore, targeted immunotherapy followed by surgical resection significantly reduced the postoperative recurrence rate at both 3 months and 1 year (9% versus 28.9%, 32.1% versus 67.9%, respectively; P=0.018), but increased the postoperative nononcologic mortality rate within 1 year (20.1% vs. 2.8%; P= 0.036). Conclusion: For HCC patients with macrovascular invasion, preoperative targeted immunotherapy significantly decreased the postoperative tumor recurrence rate while maintaining relative safety, but such a treatment may also result in chronic liver damage and increased risk of nononcologic mortality.

Pan-Cancer Analysis Identifies BCLAF1 as a Potential Biomarker for Renal Cell Carcinoma.

B-cell lymphoma-2-associated transcription factor 1 (BCLAF1) is a versatile protein involved in the regulation of gene transcription and post-transcriptional processing. Although BCLAF1 exerts a broad tumor suppressor effect or tumor promoter effect in many cancer types, the specific roles concerning its expression levels, and its impact on tumorigenesis in Renal cell carcinoma (RCC) remain unclear. Here, we utilized the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) datasets alongside R software and online tools to unravel the specific roles of BCLAF1 in 33 cancer types, including its expression levels, tumor immune and molecular subtypes, and its correlation with prognosis, diagnosis, DNA methylation, and immune microenvironment. Additionally, we carried out cell biology experiments to independently investigate the expression of BCLAF1 in RCC and its effects on tumor progression. BCLAF1 was differentially expressed in tumor tissues compared to normal tissues across various cancer types and was also differentially expressed in different immune and molecular subtypes. In RCC, patients with high BCLAF1 expression had a better prognosis and BCLAF1 was tightly correlated with the stage, gender, and histological grade of patients. Furthermore, BCLAF1 had higher DNA methylation levels and higher immune infiltration levels in tumor tissues. Additionally, cell functional experiments confirmed the low expression of BCLAF1 in RCC and that BCLAF1 significantly inhibited the proliferation, migration, and invasion, while inducing apoptosis and cell cycle arrest in RCC cells in vitro. Our study under-scored the potential of BCLAF1 as an important actor in tumorigenesis, especially concerning RCC where it may serve as an effective prognostic marker.

Hypoxia-Challenged Pancreatic Adenocarcinoma Cell-Derived Exosomal circR3HCC1L Drives Tumor Growth Via Upregulating PKM2 Through Sequestering miR-873-5p.

Pancreatic adenocarcinoma (PAAD) is a fatal disease with poor survival. Increasing evidence show that hypoxia-induced exosomes are associated with cancer progression. Here, we aimed to investigate the function of hsa_circ_0007678 (circR3HCC1L) and hypoxic PAAD cell-derived exosomal circR3HCC1L in PAAD progression. Through the exoRBase 2.0 database, we screened for a circular RNA circR3HCC1L related to PAAD. Changes of circR3HCC1L in PAAD samples and cells were analyzed with real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, migration, invasion were analyzed by colony formation, cell counting, and transwell assays. Measurements of glucose uptake and lactate production were done using corresponding kits. Several protein levels were detected by western blotting. The regulation mechanism of circR3HCC1L was verified by dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Exosomes were separated by differential ultracentrifugation. Animal experiments were used to verify the function of hypoxia-derived exosomal circR3HCC1L. CircR3HCC1L was upregulated in PAAD samples and hypoxic PAAD cells. Knockdown of circR3HCC1L decreased hypoxia-driven PAAD cell proliferation, migration, invasion, and glycolysis. Hypoxic PAAD cell-derived exosomes had higher levels of circR3HCC1L, hypoxic PAAD cell-derived exosomal circR3HCC1L promoted normoxic cancer cell malignant transformation and glycolysis in vitro and xenograft tumor growth in mouse models in vivo. Mechanistically, circR3HCC1L regulated pyruvate kinase M2 (PKM2) expression via sponging miR-873-5p. Also, PKM2 overexpression or miR-873-5p silencing offset circR3HCC1L knockdown-mediated effects on hypoxia-challenged PAAD cell malignant transformation and glycolysis. Hypoxic PAAD cell-derived exosomal circR3HCC1L facilitated PAAD progression through the miR-873-5p/PKM2 axis, highlighting the contribution of hypoxic PAAD cell-derived exosomal circR3HCC1L in PAAD.

The activation of RARα prevents surgery-induced cognitive impairments via the inhibition of neuroinflammation and the restoration of synaptic proteins in elderly mice.

Post-operative cognitive dysfunction (POCD) is a multi-etiological symptom mainly occurred in elderly people after surgery. The activation of retinoic acid receptor α (RARα), a transcriptional factor, was previously predicated to be negatively associated with the occurrence of POCD. However, the mechanisms underlying anti-POCD effects of RARα were still unclear. In this study, AM580, a selective agonist of RARα, and all-trans-retinoic acid (ATRA), a pan agonist of RAR, significantly alleviated cognitive dysfunction and increased the expression of RARα in elderly mice after surgery, which was decreased by RO41-5253, an antagonist of RARα. A bioinformatic study further predicted that the activation of RARα might produce anti-POCD effects via the restoration of synaptic proteins. Both agonists inhibited the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and the phosphorylation of nuclear factorkappa-B (NF-κB), leading to the prevention of microglial over-activation and pro-inflammatory cytokines secretion in the hippocampal regions of elderly mice after surgery. Moreover, AM580 and ATRA increased the expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95), and the phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP-response element binding protein (CREB). All these results suggested that the activation of RARα prevented surgery-induced cognitive impairments via the inhibition of neuroinflammation by the reduction of the TLR4/Myd88/NF-κB pathway and the restoration of synaptic proteins by the activation of the BDNF/ERK/CREB pathway, providing a further support that RARα could be developed as a therapeutic target for POCD.

Integrated neutrophil-to-lymphocyte ratio and handgrip strength better predict survival in patients with cancer cachexia.

OBJECTIVES: Systemic inflammation and skeletal muscle strength play crucial roles in the development and progression of cancer cachexia. In this study we aimed to evaluate the combined prognostic value of neutrophil-to-lymphocyte ratio (NLR) and handgrip strength (HGS) for survival in patients with cancer cachexia. METHODS: This multicenter cohort study involved 1826 patients with cancer cachexia. The NLR-HGS (NH) index was defined as the ratio of neutrophil-to-lymphocyte ratio to handgrip strength. Harrell's C index and receiver operating characteristic (ROC) curve analysis were used to assess the prognosis of NH. Kaplan-Meier analysis and Cox regression models were used to evaluate the association of NH with all-cause mortality. RESULTS: Based on the optimal stratification, 380 women (NH > 0.14) and 249 men (NH > 0.19) were classified as having high NH. NH has shown greater predictive value compared to other indicators in predicting the survival of patients with cancer cachexia according to the 1-, 3-, and 5-y ROC analysis and Harrell's C index calculation. Multivariate survival analysis showed that higher NH was independently associated with an increased risk of death (hazard ratio = 1.654, 95% confidence interval = 1.389-1.969). CONCLUSION: This study demonstrates that the NH index, in combination with NLR and HGS, is an effective predictor of the prognosis of patients with cancer cachexia. It can offer effective prognosis stratification and guidance for their treatment.

Binary probiotic fermentation promotes signal (cyclic AMP) exchange to increases the number of viable probiotics, anthocyanins and polyphenol content, and the odor scores of wolfberry fermented beverages.

The effects and underlying molecular mechanisms of binary probiotics (Lactiplantibacillus plantarum subsp. plantarum CGMCC 1.5953 and Lacticaseibacillus casei CGMCC 1.5956) on the quality of wolfberry fermented beverages (WFB) were investigated. The results indicated that binary probiotics increased the number of probiotics, anthocyanin (89.92 ± 1.64 mg/L), polyphenol content (283.04 ± 3.81 µg/mL), and odor score (24.19) in WFB. Metabolomics found that they could enhance signal exchange (cyclic AMP) between binary probiotics and improve the utilization of citrulline, d-proline, d-glucose, and d-galactose through galactose metabolism and amino acid biosynthesis pathway to promote probiotics growth. Furthermore, HS-SPME-GC-MS and GS-IMS revealed that the improvement in flavor was mainly due to an increase in the content of the aromatic flavor substances 3-heptanol, glutaraldehyde, and 2-heptanone, and a decrease in the content of the off-flavor substances methyl isobutyl ketone-D and 2-undecanone. This is strategically important for the development of WFB with high probiotic content and unique flavor.

Regulating the catalytic behaviour of iron oxyhydroxide by introducing Ni sites for facilitating polysulfide anchoring and conversion.

The sluggish conversion kinetics and notorious shuttle effect of polysulfides are critical hindrances to practical implementation of lithium-sulfur batteries. Herein, bimetallic oxyhydroxide (FeNiOOH) as a functional sulfur host is proposed to overcome these obstacles. The introduction of Ni sites can modulate the electronic structure of the active sites to implement strong soluble polysulfide species immobilization and accelerate the conversion reaction kinetics of polysulfides, resulting in improved sulfur utilization and reduced polarization during the electrochemical reaction process. Benefiting from these advantages, FeNiOOH enables the sulfur cathode to deliver superior rate capability and cycling stability.

Clinical evolution of antisynthetase syndrome-associated interstitial lung disease after COVID-19 in a man with Klinefelter syndrome: A case report.

BACKGROUND: This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome (AS) following coronavirus disease 2019 (COVID-19) in a 33-year-old man diagnosed with Klinefelter syndrome (KS). CASE SUMMARY: A 33-year-old man with a diagnosis of KS was admitted to the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of COVID-19. Computed tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs, accompanied by signs of partial bronchial inflation. Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen. A biopsy specimen revealed organizing pneumonia with alveolar septal thickening. Additionally, extensive auto-antibody tests showed strong positivity for anti-SSA, anti-SSB, anti-Jo-1, and anti-Ro-52. Following multidisciplinary discussions, the patient received a final diagnosis of AS, leading to rapidly progressing respiratory failure. CONCLUSION: This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.

A COX2-targeting cancer-specific fluorescent probe for hydrogen sulfide detection in living cells, Caenorhabditis elegans, and zebrafish.

A novel cyclooxygenase-2 (COX-2) targeted H2S-activated cancer-specific fluorescent probe, namely, COX2-H2S, was designed and synthesized, with naphthalimide as the fluorophore and indomethacin as the targeting group. This H2S-sensing probe was developed to differentiate tumor cells from normal cells and was tested in living cells, Caenorhabditis elegans (C. elegans), and zebrafish. The probe could successfully be used for imaging endogenous and exogenous H2S in living cells, demonstrating high sensitivity and specificity and strong anti-interference. COX2-H2S had the ability to not only discern cancer cells from normal cells but also specifically recognize 9L/lacZ cells from other glioblastoma cells (U87-MG and LN229). It could also be successfully applied for the fluorescent live imaging of H2S in both C. elegans and zebrafish.

miRNome targeting NF-κB signaling orchestrates macrophage-triggered cancer metastasis and recurrence.

Whether and how tumor intrinsic signature determines macrophage-elicited metastasis remain elusive. Here, we show, in detailed studies of data regarding 7,477 patients of 20 types of human cancers, that only 13.8% ± 2.6%/27.9% ± 3.03% of patients with high macrophage infiltration index exhibit early recurrence/vascular invasion. In parallel, although macrophages enhance the motility of various hepatoma cells, their enhancement intensity is significantly heterogeneous. We identify that the expression of malignant Dicer, a ribonuclease that cleaves miRNA precursors into mature miRNAs, determines macrophage-elicited metastasis. Mechanistically, the downregulation of Dicer in cancer cells leads to defects in miRNome targeting NF-κB signaling, which in turn enhances the ability of cancer cells to respond to macrophage-related inflammatory signals and ultimately promotes metastasis. Importantly, transporting miR-26b-5p, the most potential miRNA targeting NF-κB signaling in hepatocellular carcinoma, can effectively reverse macrophage-elicited metastasis of hepatoma in vivo. Our results provide insights into the crosstalk between Dicer-elicited miRNome and cancer immune microenvironments and suggest that strategies to remodel malignant cell miRNome may overcome pro-tumorigenic activities of inflammatory cells.

Imaging, pathology, and diagnosis of solitary fibrous tumor of the pancreas: A case report and review of literature.

BACKGROUND: A solitary fibrous tumor (SFT) is often located in the pleura, while SFT of the pancreas is extremely rare. Here, we report a case of SFT of the pancreas and discuss imaging, histopathology, and immunohistochemistry for accurate diagnosis and treatment. CASE SUMMARY: A 54-year-old man presented to our hospital with pancreatic occupancy for over a month. There were no previous complaints of discomfort. His blood pressure was normal. Blood glucose, tumor markers, and enhanced computed tomography (CT) suggested a malignant tumor. Because the CT appearance of pancreatic cancer varies, we could not confirm the diagnosis; therefore, we performed endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). Pathology and immunohistochemistry were consistent with SFT of the pancreas. The postoperative pathology and immunohistochemistry were consistent with the puncture results. The patient presented for a follow-up examination one month after discharge with no adverse effects. CONCLUSION: Other diseases must be excluded in patients with a pancreatic mass that cannot be diagnosed. CT and pathological histology have diagnostic value for pancreatic tumors. Endoscopic puncture biopsy under ultrasound can help diagnose pancreatic masses that cannot be diagnosed preoperatively. Surgery is an effective treatment for SFT of the pancreas; however, long-term follow-up is strongly recommended because of the possibility of malignant transformation of the tumor.

BCLAF1 binds SPOP to stabilize PD-L1 and promotes the development and immune escape of hepatocellular carcinoma.

Interaction between programmed death-1 (PD-1) ligand 1 (PD-L1) on tumor cells and PD-1 on T cells allows tumor cells to evade T cell-mediated immune surveillance. Strategies targeting PD-1/PD-L1 have shown clinical benefits in a variety of cancers. However, limited response rates in hepatocellular carcinoma (HCC) have prompted us to investigate the molecular regulation of PD-L1. Here, we identify B cell lymphoma-2-associated transcription factor 1 (BCLAF1) as a key PD-L1 regulator in HCC. Specifically, BCLAF1 interacts with SPOP, an E3 ligase that mediates the ubiquitination and degradation of PD-L1, thereby competitively inhibiting SPOP-PD-L1 interaction and subsequent ubiquitination and degradation of PD-L1. Furthermore, we determined an SPOP-binding consensus (SBC) motif mediating the BCLAF1-SPOP interaction on BCLAF1 protein and mutation of BCLAF1-SBC motif disrupts the regulation of the SPOP-PD-L1 axis. In addition, BCLAF1 expression was positively correlated with PD-L1 expression and negatively correlated with biomarkers of T cell activation, including CD3 and CD8, as well as with the level of immune cell infiltration in HCC tissues. Besides, BCLAF1 depletion leads to a significant reduction of PD-L1 expression in vitro, and this reduction of PD-L1 promoted T cell-mediated cytotoxicity. Notably, overexpression of BCLAF1 sensitized tumor cells to checkpoint therapy in an in vitro HCC cells-Jurkat cells co-culture model, whereas BCLAF1-SBC mutant decreased tumor cell sensitivity to checkpoint therapy, suggesting that BCLAF1 and its SBC motif serve as a novel therapeutic target for enhancing anti-tumor immunity in HCC.

Heterogeneous DNA hydrogel loaded with Apt02 modified tetrahedral framework nucleic acid accelerated critical-size bone defect repair.

Segmental bone defects, stemming from trauma, infection, and tumors, pose formidable clinical challenges. Traditional bone repair materials, such as autologous and allogeneic bone grafts, grapple with limitations including source scarcity and immune rejection risks. The advent of nucleic acid nanotechnology, particularly the use of DNA hydrogels in tissue engineering, presents a promising solution, attributed to their biocompatibility, biodegradability, and programmability. However, these hydrogels, typically hindered by high gelation temperatures (∼46 °C) and high construction costs, limit cell encapsulation and broader application. Our research introduces a novel polymer-modified DNA hydrogel, developed using nucleic acid nanotechnology, which gels at a more biocompatible temperature of 37 °C and is cost-effective. This hydrogel then incorporates tetrahedral Framework Nucleic Acid (tFNA) to enhance osteogenic mineralization. Furthermore, considering the modifiability of tFNA, we modified its chains with Aptamer02 (Apt02), an aptamer known to foster angiogenesis. This dual approach significantly accelerates osteogenic differentiation in bone marrow stromal cells (BMSCs) and angiogenesis in human umbilical vein endothelial cells (HUVECs), with cell sequencing confirming their targeting efficacy, respectively. In vivo experiments in rats with critical-size cranial bone defects demonstrate their effectiveness in enhancing new bone formation. This innovation not only offers a viable solution for repairing segmental bone defects but also opens avenues for future advancements in bone organoids construction, marking a significant advancement in tissue engineering and regenerative medicine.

Targeting Ferroptosis-Elicited Inflammation Suppresses Hepatocellular Carcinoma Metastasis and Enhances Sorafenib Efficacy.

Triggering ferroptosis, an iron-dependent form of cell death, has recently emerged as an approach for treating cancer. A better understanding of the role and regulation of ferroptosis is needed to realize the potential of this therapeutic strategy. Here, we observed extensive activation of ferroptosis in hepatoma cells and human hepatocellular carcinoma (HCC) cases. Patients with low to moderate activation of ferroptosis in tumors had the highest risk of recurrence compared to patients with no or high ferroptosis. Upon encountering ferroptotic liver cancer cells, aggregated macrophages efficiently secreted proinflammatory IL1ß to trigger neutrophil-mediated sinusoidal vascular remodeling, thereby creating favorable conditions for aggressive tumor growth and lung metastasis. Mechanistically, hyaluronan fragments released by cancer cells acted via an NF-κB-dependent pathway to upregulate IL1ß precursors and the NLRP3 inflammasome in macrophages, and oxidized phospholipids secreted by ferroptotic cells activated the NLRP3 inflammasome to release functional IL1ß. Depleting either macrophages or neutrophils or neutralizing IL1ß in vivo effectively abrogated ferroptosis-mediated liver cancer growth and lung metastasis. More importantly, the ferroptosis-elicited inflammatory cellular network served as a negative feedback mechanism that led to therapeutic resistance to sorafenib in HCC. Targeting the ferroptosis-induced inflammatory axis significantly improved the therapeutic efficacy of sorafenib in vivo. Together, this study identified a role for ferroptosis in promoting HCC by triggering a macrophage/IL1ß/neutrophil/vasculature axis. SIGNIFICANCE: Ferroptosis induces a favorable tumor microenvironment and supports liver cancer progression by stimulating an inflammatory cellular network that can be targeted to suppress metastasis and improve the efficacy of sorafenib.

Recent research advances on polysaccharide-, peptide-, and protein-based hemostatic materials: A review.

Hemorrhage is a potentially life-threatening emergency that can occur at any time or place. Whether traumatic, congenital, surgical, disease-related, or drug-induced, bleeding can lead to severe complications or death. Therefore, the development of efficient hemostatic materials is critical. However, the results and prognosis demonstrated by clinical means of hemostasis do not reach expectations. With the development of technology, novel hemostatic materials have been developed from polysaccharides (chitosan, hyaluronic acid, alginate, cellulose, cyclodextrins, starch, dextran, and carrageenan), peptides (self-assembling peptides), and proteins (silk fibroin, collagen, gelatin, keratin, and thrombin). These new materials exhibit high hemostatic efficacy due to the enhancement or interaction of various hemostatic mechanisms. The main forms include adhesives, sealants, bandages, hemostatic powders, and hemostatic sponges. This article introduces the clotting process and principles of hemostatic methods and reviews the research on polysaccharide-, peptide-, and protein-based hemostatic materials in the last five years. The design ideas and hemostatic principles of polysaccharide-, peptide-, and protein-based hemostatic materials are mainly introduced. Finally, we summarize material designs, advantages, disadvantages, and challenges regarding hemostatic materials.

Variety of femoral anteversion and its measurement in cementless total hip arthroplasty: Does robotic technology improve accuracy?

BACKGROUND: High-performance total hip arthroplasty (THA) depends on the accurate position of components. However, femoral anteversion is variable, and current studies only used traditional instruments to evaluate it, such as protractor and spirit level with limited cases. This study aimed to identify the variability in the measured femoral native anteversion and intraoperative stem anteversion under different measurement methods, including intraoperative robotic method. We hypothesized that robotic technology was more accurate than traditional instruments for femoral anteversion evaluation. METHODS: This study included 117 hips of patients who underwent robotic-assisted THA between November 2019 and March 2021. Preoperative native femoral anteversion was measured using a robotic system. Intraoperative femoral stem anteversion was evaluated visually, and then measured with a goniometer and a robotic system, respectively. Variability in the measured femoral native anteversion and intraoperative femoral stem anteversion was calculated and compared. Intraclass correlation coefficient (ICC) and Pearson correlation analysis were used to assess the consistency and correlation of anteversion of different measurements and postoperative CT-measured stem anteversion, respectively. RESULTS: The result of measurement for preoperative native femoral anteversion was more variable than the intraoperative robotic-measured stem anteversion. Intraoperative robotic-measured stem version showed the highest correlation with postoperative CT measurement of stem version (r = 0.806, P < 0.001), while intraoperative surgeon estimation had the lowest correlation coefficient (r = 0.281, P = 0.025). As for the consistency with postoperative CT measurement of femoral stem anteversion, the intraoperative robotic-measured femoral stem version also had the highest value (ICC = 0.892, P < 0.001). CONCLUSION: Native femoral anteversion was variable preoperatively. Using cementless stems, anteversion was also highly variable. Robotic assessment for stem anteversion during surgery was more consistent with the final position than the preoperative assessment and conventional intraoperative estimation.

Label-free screening of common urinary system tumors from blood plasma based on surface-enhanced Raman spectroscopy.

BACKGROUND: The incidence of common urinary system tumors has been rising rapidly in recent years, and most urinary system-derived tumors lack specific biomarkers. OBJECTIVES: To explore the efficacy of surface-enhanced Raman spectroscopy (SERS) of blood plasma in screening three common urinary system tumors, including bladder cancer (BC), prostate cancer (PCa), and renal cell carcinoma (RCC). METHODS: SERS plasma spectra from 125 plasma samples, including 25 PCa, 38 RCC, 24 BC patients, and 38 normal volunteers, were collected. All candidates had no other comorbidities. The Diagnosis was based on the combination of Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA), and the effectiveness of the diagnostic algorithms was verified using the Receiver Operating Characteristic Curve (ROC). RESULTS: There are significant differences in SERS signals between PCa, BC, RCC, and normal plasma, especially at 639, 889, 1010, 1136, and 1205 cm-1. The PCA-LDA results show that high sensitivity (100 %), specificity (100 %), and accuracy (100 %) could be achieved for screening the PCa, RCC, BC group vs. the normal group, the PCa group vs. the BC and RCC group, respectively. The diagnostic sensitivity, specificity, and accuracy for the BC group vs. the RCC group are 79.2 %, 71.1 %, and 75.15 %, respectively. The integrated area under the ROC curve (AUC) is 1.0, 1.0, and 1.0 for the PCa, RCC, and BC group vs. the normal group, respectively. The AUC of the PCa group vs. the BC group and RCC group and the BC group vs. the RCC group are 1.0, 1.0, and 0.842, respectively. CONCLUSIONS: Label-free plasma-SERS technology with PCA-LDA analysis could be a useful screening method for detecting urinary system tumors (PCa, RCC, and BC) in this exploratory study.

Phenethyl isothiocyanate inhibits metastasis potential of non-small cell lung cancer cells through FTO mediated TLE1 m6A modification.

N6-methyladenosine (m6A) modification is a prevalent RNA epigenetic modification, which plays a crucial role in tumor progression including metastasis. Isothiocyanates (ITCs) are natural compounds and inhibit the tumorigenesis of various cancers. Our previous studies show that ITCs inhibit the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells, and have synergistic effects with chemotherapy drugs. In this study, we investigated the molecular mechanisms underlying the inhibitory effects of ITCs on cancer cell metastasis. We showed that phenethyl isothiocyanate (PEITC) dose-dependently inhibited the cell viability of both NSCLC cell lines H1299 and H226 with IC50 values of 17.6 and 15.2 µM, respectively. Furthermore, PEITC dose-dependently inhibited the invasion and migration of H1299 and H226 cells. We demonstrated that PEITC treatment dose-dependently increased m6A methylation levels and inhibited the expression of the m6A demethylase fat mass and obesity-associated protein (FTO) in H1299 and H226 cells. Knockdown of FTO significantly increased m6A methylation in H1299 and H226 cells, impaired their abilities of invasion and migration in vitro, and enhanced the inhibition of PEITC on tumor growth in vivo. Overexpression of FTO promoted the migration of NSCLC cells, and also mitigated the inhibitory effect of PEITC on migration of NSCLC cells. Furthermore, we found that FTO regulated the mRNA m6A modification of a transcriptional co-repressor Transducin-Like Enhancer of split-1 (TLE1) and further affected its stability and expression. TCGA database analysis revealed TLE1 was upregulated in NSCLC tissues compared to normal tissues, which might be correlated with the metastasis status. Moreover, we showed that PEITC suppressed the migration of NSCLC cells by inhibiting TLE1 expression and downstream Akt/NF-κB pathway. This study reveals a novel mechanism underlying ITC's inhibitory effect on metastasis of lung cancer cells, and provided valuable information for developing new therapeutics for lung cancer by targeting m6A methylation.

Two-stage multi-task deep learning framework for simultaneous pelvic bone segmentation and landmark detection from CT images.

PURPOSE: Pelvic bone segmentation and landmark definition from computed tomography (CT) images are prerequisite steps for the preoperative planning of total hip arthroplasty. In clinical applications, the diseased pelvic anatomy usually degrades the accuracies of bone segmentation and landmark detection, leading to improper surgery planning and potential operative complications. METHODS: This work proposes a two-stage multi-task algorithm to improve the accuracy of pelvic bone segmentation and landmark detection, especially for the diseased cases. The two-stage framework uses a coarse-to-fine strategy which first conducts global-scale bone segmentation and landmark detection and then focuses on the important local region to further refine the accuracy. For the global stage, a dual-task network is designed to share the common features between the segmentation and detection tasks, so that the two tasks mutually reinforce each other's performance. For the local-scale segmentation, an edge-enhanced dual-task network is designed for simultaneous bone segmentation and edge detection, leading to the more accurate delineation of the acetabulum boundary. RESULTS: This method was evaluated via threefold cross-validation based on 81 CT images (including 31 diseased and 50 healthy cases). The first stage achieved DSC scores of 0.94, 0.97, and 0.97 for the sacrum, left and right hips, respectively, and an average distance error of 3.24 mm for the bone landmarks. The second stage further improved the DSC of the acetabulum by 5.42%, and this accuracy outperforms the state-of-the-arts (SOTA) methods by 0.63%. Our method also accurately segmented the diseased acetabulum boundaries. The entire workflow took ~ 10 s, which was only half of the U-Net run time. CONCLUSION: Using the multi-task networks and the coarse-to-fine strategy, this method achieved more accurate bone segmentation and landmark detection than the SOTA method, especially for diseased hip images. Our work contributes to accurate and rapid design of acetabular cup prostheses.