An evaluation model of hepatic steatosis based on CT value and serum uric acid/HDL cholesterol ratio can predict intrahepatic recurrence of colorectal cancer liver metastasis.

BACKGROUND: Intrahepatic recurrence is one of the main causes of treatment failure in patients with colorectal cancer liver metastasis (CRLM). Hepatic steatosis was reported to provide fertile soil for metastasis. The effect of irinotecan-inducted hepatic steatosis on the progression of liver metastasis remains to be verified. Therefore, we aim to clarify the effect of hepatic steatosis on postoperative intrahepatic recurrence in CRLM and whether it is relevant to irinotecan-based chemotherapy. METHODS: Data for a total of 284 patients undergoing curative surgical treatment for CRLMs were retrospectively reviewed between March 2007 and June 2018. Hepatic steatosis score (HSS) was established by combining Liver to Spleen CT ratio (LSR) and Uric acid to HDL-cholesterol ratio (UHR) to detect the presence of hepatic steatosis. RESULTS: The evaluation model is consistent with pathological results and has high prediction ability and clinical application value. Patients with HSS high risk (HSS-HR) had significantly worse prognosis than those with HSS low risk (HSS-LR) (3-year intrahepatic RFS: 42.7% vs. 29.4%, P = 0.003; 5-year OS: 45.7% vs. 26.5%, P = 0.002). Univariate and multivariate analysis confirmed its essential role in the prediction of intrahepatic RFS. Besides, patients treated with preoperative irinotecan chemotherapy were more likely to end up with HSS-HR than those with non-irinotecan chemotherapy (63.3% vs. 21.8%, P < 0.001). Furthermore, irinotecan chemotherapy is relevant to worse prognosis in baseline HSS-HR patients. CONCLUSION: In summary, patients with HSS-HR had significantly worse 5-year OS and 3-year intrahepatic RFS. Irinotecan chemotherapy is more likely to lead to HSS-HR and pre-existing hepatic steatosis may be a worse prognostic factor limiting patients underwent IRI-based chemotherapy.

Prediction of Follicular Thyroid Neoplasm and Malignancy of Follicular Thyroid Neoplasm Using Multiparametric MRI.

The study aims to evaluate multiparametric magnetic resonance imaging (MRI) for differentiating Follicular thyroid neoplasm (FTN) from non-FTN and malignant FTN (MFTN) from benign FTN (BFTN). We retrospectively analyzed 702 postoperatively confirmed thyroid nodules, and divided them into training (n = 482) and validation (n = 220) cohorts. The 133 FTNs were further split into BFTN (n = 116) and MFTN (n = 17) groups. Employing univariate and multivariate logistic regression, we identified independent predictors of FTN and MFTN, and subsequently develop a nomogram for FTN and a risk score system (RSS) for MFTN prediction. We assessed performance of nomogram through its discrimination, calibration, and clinical utility. The diagnostic performance of the RSS for MFTN was further compared with the performance of the Thyroid Imaging Reporting and Data System (TIRADS). The nomogram, integrating independent predictors, demonstrated robust discrimination and calibration in differentiating FTN from non-FTN in both training cohort (AUC = 0.947, Hosmer-Lemeshow P = 0.698) and validation cohort (AUC = 0.927, Hosmer-Lemeshow P = 0.088). Key risk factors for differentiating MFTN from BFTN included tumor size, restricted diffusion, and cystic degeneration. The AUC of the RSS for MFTN prediction was 0.902 (95% CI 0.798-0.971), outperforming five TIRADS with a sensitivity of 73.3%, specificity of 95.1%, accuracy of 92.4%, and positive and negative predictive values of 68.8% and 96.1%, respectively, at the optimal cutoff. MRI-based models demonstrate excellent diagnostic performance for preoperative predicting of FTN and MFTN, potentially guiding clinicians in optimizing therapeutic decision-making.

Orientation transitions and chiral assemblies of para-terphenyl molecules on Cd(0001).

The interplay between orientation transition and chiral self-assemblies of para-terphenyl (P3P) molecules on the Cd(0001) surface has been investigated using low temperature scanning tunneling microscopy and density functional theory calculations. Three distinct molecular orientations have been discerned from the self-assembled thin films of P3P. At the low coverage, flat-lying molecules appear in the homochiral domains with the incommensurate registry to the substrate. With the coverage increasing, the incoming molecules are incorporated into the first layer with edge-on orientation and form the self-assembled zigzag chains. The alternative arrangement of zigzag chains with opposite chirality leads to the formation of a c(4 × 2) superstructure, in which the tilted molecules exhibit orientational frustration and fuzzy noises. The analysis of the tunneling spectra reveals that the electronic structure of P3P layers is contingent upon the hybridization between the electronic states of P3P molecules and the Cd(0001) surface. These results provide important insights into the interplay between orientational transition and chiral assembly of P3P molecules on metal substrates.

Discovery of a novel DYRK1A inhibitor with neuroprotective activity by virtual screening and in vitro biological evaluation.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is implicated in accumulation of amyloid ß-protein (Aß) and phosphorylation of Tau proteins, and thus represents an important therapeutic target for neurodegenerative diseases. Though many DYRK1A inhibitors have been discovered, there is still no marketed drug targeting DYRK1A. This is partly due to the lack of effective and safe chemotypes. Therefore, it is still necessary to identify new classes of DYRK1A inhibitors. By performing virtual screening with the workflow mainly composed of pharmacophore modeling and molecular docking as well as the following DYRK1A inhibition assay, we identified compound L9, ((Z)-1-(((5-phenyl-1H-pyrazol-4-yl)methylene)-amino)-1H-tetrazol-5-amine), as a moderately active DYRK1A inhibitor (IC50: 1.67 µM). This compound was structurally different from the known DYRK1A inhibitors, showed a unique binding mode to DYRK1A. Furthermore, compound L9 showed neuroprotective activity against okadaic acid (OA)-induced injury in the human neuroblastoma cell line SH-SY5Y by regulating the expression of Aß and phosphorylation of Tau protein. This compound was neither toxic to the SH-SY5Y cells nor to the human normal liver cell line HL-7702 (IC50: >100 µM). In conclusion, we have identified a novel DYRK1A inhibitor with neuroprotective activity through virtual screening and in vitro biological evaluation, which holds the promise for further study.

The Correlation of Centromere Protein Q with Diagnosis and Prognosis in Hepatocellular Carcinoma.

Introduction: Hepatocellular carcinoma (HCC) is one of the major types of liver cancer. Previous studies have shown that the centromere protein family is associated with malignant biological behaviors such as HCC proliferation. As a member of the centromere protein family, centromere protein Q (CENPQ) is closely associated with immunotherapy and immune cell infiltration in various tumors. However, the role and mechanism of CENPQ in HCC remain unclear. Methods: Multiple public databases and RT-qPCR were used to study the expression of CENPQ in HCC. Based on TCGA data, the correlation between CENPQ and clinicopathological characteristics and prognosis of HCC patients was analyzed, and its diagnostic value was evaluated. The potential biological functions of CENPQ in HCC were explored by functional enrichment analysis of differentially expressed genes. The distribution of tumor-infiltrating immune cell types was assessed using single-sample GSEA, and immune checkpoint gene expression was analyzed using Spearman correlation. Subsequently, loss-of-function experiments were performed to determine the function of CENPQ on the cell cycle and proliferation of HCC cells in vitro. Results: CENPQ was found highly expressed in HCC and correlated with weight, BMI, age, AFP, T stage, pathologic stage, histologic grade, and prothrombin time (all p < 0.05). ROC and Kaplan-Meier analyses indicated that CENPQ may be potentially used as a diagnostic marker for HCC (AUC = 0.881), and its upregulation is associated with decreased OS (p = 0.002), DSS (p < 0.001), and PFI (p = 0.002). Functional enrichment analysis revealed an association of CENPQ with biological processes such as immune cell infiltration, cell cycle, and hippo-merlin signaling deregulation in HCC. Furthermore, knockdown of CENPQ manifested in HCC cells with G0/1 phase cycle arrest and decreased proliferative capacity. Conclusion: CENPQ expression was higher in HCC tissues than in normal liver tissues. It was significantly associated with poor prognosis, immune cell infiltration, cell cycle, and proliferation. Therefore, CENPQ may become a promising prognostic biomarker for HCC patients.

The adenosine A2A receptor in human sperm: its role in sperm motility and association with in vitro fertilization outcomes.

Background: The involvement of ATP and cAMP in sperm function has been extensively documented, but the understanding of the role of adenosine and adenosine receptors remains incomplete. This study aimed to examine the presence of adenosine A2A receptor (A2AR) and study the functional role of A2AR in human sperm. Methods: The presence and localization of A2AR in human sperm were examined by western blotting and immunofluorescence assays. The functional role of A2AR in sperm was assessed by incubating human sperm with an A2AR agonist (regadenoson) and an A2AR antagonist (SCH58261). The sperm level of A2AR was examined by western blotting in normozoospermic and asthenozoospermic men to evaluate the association of A2AR with sperm motility and in vitro fertilization (IVF) outcomes. Results: A2AR with a molecular weight of 43 kDa was detected in the tail of human sperm. SCH58261 decreased the motility, penetration ability, intracellular Ca2+ concentration, and CatSper current of human sperm. Although regadenoson did not affect these sperm parameters, it alleviated the adverse effects of SCH58261 on these parameters. In addition, the mean level of A2AR in sperm from asthenozoospermic men was lower than that in sperm from normozoospermic men. The sperm level of A2AR was positively correlated with progressive motility. Furthermore, the fertilization rate during IVF was lower in men with decreased sperm level of A2AR than in men with normal sperm level of A2AR. Conclusions: These results indicate that A2AR is important for human sperm motility and is associated with IVF outcome.

Tree peony seed oil alleviates hyperlipidemia and hyperglycemia by modulating gut microbiota and metabolites in high-fat diet mice.

With the changes of people's lifestyle, hyperlipidemia and hyperglycemia which were induced from a diet high in both fat and sugar have become serious health concerns. Tree peony seed oil (PSO) is a novel kind of edible oil that shows great potential in the food industry because of its high constituent of unsaturated fatty acids. Based 16S rRNA and gut untargeted metabolomics, this study elucidated that the mechanism of PSO regulating blood glucose (Glu) and lipids. The impact of PSO on gut microbiota balance and gut metabolites of mice with a high-fat diet (HFD) was evaluated. The findings indicated that PSO decreased HFD mice's body weight and fat accumulation, ameliorating the levels of blood lipid, reduced liver fat vacuole levels. What's more PSO modulated the proportion of gut microbiota in HFD mice and enhanced the abundance of probiotics. Furthermore, untargeted metabolomic analysis revealed that PSO not only impacted the generation of short-chain fatty acids (SCFAs) by gut microorganism and altered metabolic pathway but exerted influence on secondary bile acids (BA), amino acid metabolism, and various other metabolites. These results suggested that PSO has the potential function for mitigating HFD-induced hyperlipidemia and hyperglycemia by regulating gut microbiota and host metabolism.

CoS2/carbon network flexible film with Co-N bond/π-π interaction enables superior mechanical properties and high-rate sodium ion storage.

Flexible electrodes based on conversion-type materials have potential applications in low-cost and high-performance flexible sodium-ion batteries (FSIBs), owing to their high theoretical capacity and appropriate sodiation potential. However, they suffer from flexible electrodes with poor mechanical properties and sluggish reaction kinetics. In this study, freestanding CoS2 nanoparticles coupled with graphene oxides and carbon nanotubes (CoS2/GO/CNTs) flexible films with robust and interconnected architectures were successfully synthesized. CoS2/GO/CNTs flexible film displays high electronic conductivity and superior mechanical properties (average tensile strength of 21.27 MPa and average toughness of 393.18 KJ m-3) owing to the defect bridge for electron transfer and the formation of the π-π interactions between CNTs and GO. In addition, the close contact between the CoS2 nanoparticles and carbon networks enabled by the Co-N chemical bond prevents the self-aggregation of the CoS2 nanoparticles. As a result, the CoS2/GO/CNTs flexible film delivered superior rate capability (213.5 mAh g-1 at 6 A g-1, better than most reported flexible anode) and long-term cycling stability. Moreover, the conversion reaction that occurred in the CoS2/GO/CNTs flexible film exhibited pseudocapacitive behavior. This study provides meaningful insights into the development of flexible electrodes with superior mechanical properties and electrochemical performance for energy storage.

Jingangteng capsules ameliorate liver lipid disorders in diabetic rats by regulating microflora imbalances, metabolic disorders, and farnesoid X receptor.

BACKGROUND: The plant Smilax china L., also known as Jingangteng, is suspected of regulating glucose and lipid metabolism. Jingangteng capsules (JGTCs) are commonly used to treat gynecological inflammation in clinical practice. However, it is not clear whether JGTCs can regulate glucose and lipid metabolism, and the mechanism is unclear. PURPOSE: To investigate the impact and mechanism of action of JGTCs on diabetes and liver lipid disorders in rats. METHODS: The chemical constituents of JGTCs were examined using ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. A high-fat diet and streptozotocin-induced diabetes model was used to evaluate anti-diabetic effects by assessing blood glucose and lipid levels and liver function. The mechanism was explored using fecal 16S rRNA gene sequencing and metabolomics profiling, reverse transcription-quantiative polymerase chain reaction (RT-qPCR), and Western blot analysis. RESULTS: Thirty-three components were identified in JGTCs. The serological and histomorphological assays revealed that JGTC treatment reduced levels of blood glucose and lipids, aspartate aminotransferase, alanine aminotransferase, and lipid accumulation in the liver of diabetic rats. According to 16S rDNA sequencing, JGTCs improved species richness and diversity in diabetic rats' intestinal flora and restored 22 dysregulated bacteria to control levels. Fecal metabolomics analysis showed that the altered fecal metabolites were rich in metabolites, such as histidine, taurine, low taurine, tryptophan, glycerophospholipid, and arginine. Serum metabolomics analysis indicated that serum metabolites were enriched in the metabolism of glycerophospholipids, fructose and mannose, galactose, linoleic acid, sphingolipids, histidine, valine, leucine and isoleucine biosynthesis, and tryptophan metabolism. Heatmaps revealed a strong correlation between metabolic parameters and gut microbial phylotypes. Molecular biology assays showed that JGTC treatment reversed the decreased expression of farnesoid X receptor (FXR) in the liver of diabetic rats and inhibited the expression of lipogenic genes (Srebp1c and FAS) as well as inflammation-related genes (interleukin (IL)-ß, tumor necrosis factor (TNF)-α, and IL-6). Liver metabolomics analysis indicated that JGTC could significantly regulate a significant number of bile acid metabolites associated with FXR, such as glyco-beta-muricholic acid, glycocholic acid, tauro-beta-muricholic acid, and tauro-gamma-muricholic acid. CONCLUSIONS: This was the first study to investigate the mechanisms of JGTCs' effects on liver lipid disorders in diabetic rats. JGTCs inhibited liver lipid accumulation and inflammatory responses in diabetic rats by affecting intestinal flora and metabolic disorders and regulating FXR-fat synthesis-related pathways to alleviate diabetic lipid disorders.

Large-scale photonic computing with nonlinear disordered media.

Neural networks find widespread use in scientific and technological applications, yet their implementations in conventional computers have encountered bottlenecks due to ever-expanding computational needs. Photonic computing is a promising neuromorphic platform with potential advantages of massive parallelism, ultralow latency and reduced energy consumption but mostly for computing linear operations. Here we demonstrate a large-scale, high-performance nonlinear photonic neural system based on a disordered polycrystalline slab composed of lithium niobate nanocrystals. Mediated by random quasi-phase-matching and multiple scattering, linear and nonlinear optical speckle features are generated as the interplay between the simultaneous linear random scattering and the second-harmonic generation, defining a complex neural network in which the second-order nonlinearity acts as internal nonlinear activation functions. Benchmarked against linear random projection, such nonlinear mapping embedded with rich physical computational operations shows improved performance across a large collection of machine learning tasks in image classification, regression and graph classification. Demonstrating up to 27,648 input and 3,500 nonlinear output nodes, the combination of optical nonlinearity and random scattering serves as a scalable computing engine for diverse applications.

Ambient Air Processed Inverted Inorganic Perovskite Solar Cells with over 21% Efficiency Enabled by Multifunctional Ethacridine Lactate.

All-inorganic cesium lead triiodide perovskites (CsPbI3) have attracted increasing attention due to their good thermal stability, remarkable optoelectronic properties, and adaptability in tandem solar cells. However, N2-filled glovebox is generally required to strictly control the humidity during film fabrication due to the moisture-induced black-to-yellow phase transition, which remains a great hinderance for further commercialization. Herein, we report an effective approach via incorporating multifunctional ethacridine lactate (EAL) to mitigate moisture invasion and enable the fabrication of efficient inverted (p-i-n) CsPbI3 perovskite solar cells (PSCs) under ambient condition. It is revealed that the lactate anions accelerate the crystallization of CsPbI3, shortening the exposure time to moisture during film fabrication. Meanwhile, the conjugated backbone and multiple functional groups in the ethacridine cations can interact with I- and Pb2+ to reduce the undesired defects, stabilize the perovskite structure and facilitate the charge transport in the film. Moreover, EAL incorporation also leads to better energy alignment, thus favoring charge extraction at both upper and bottom interfaces. Consequently, the device efficiency and stability are enormously enhanced, with the champion efficiency reaching 21.08%. This even surpasses the highest value reported for the devices fabricated in glovebox, representing a record efficiency of inverted all-inorganic PSCs.

Study on the Relationship between sLOX-1, S100A12, D-dimer, and Cerebral Hemorrhage Transformation after Intravenous Thrombolysis in Stroke.

Objective: This study examines the relationship between serum biomarkers sLOX-1, S100A12, D-dimer and the risk of cerebral hemorrhage transformation following intravenous thrombolysis in stroke patients. Methods: We retrospectively analyzed 161 stroke patients who underwent intravenous thrombolysis at our hospital from March 2021 to March 2023. Patients were categorized into hemorrhagic transformation (n=35) and non-hemorrhagic transformation groups (n=126) based on head CT scans conducted within 3 days post-treatment. We compared serum levels of sLOX-1, S100A12, and D-dimer between the groups and analyzed clinical data to evaluate factors influencing hemorrhagic transformation. Results: No significant differences were found in demographics, medical history, or stroke characteristics between the groups (P > .05). The hemorrhagic transformation group exhibited higher NIHSS scores, WBC levels, and lower UA levels (P < .05). Notably, sLOX-1, S100A12, and D-dimer levels were significantly elevated in the hemorrhagic group (P < .05). Multivariate regression and ROC curve analyses indicated these biomarkers and NIHSS scores significantly predict cerebral hemorrhage post-thrombolysis (P < .05). Conclusion: Elevated sLOX-1, S100A12, and D-dimer levels are associated with an increased risk of cerebral hemorrhage transformation after thrombolysis in stroke patients. These biomarkers along with NIHSS and NIHSS scores, hold diagnostic value for predicting hemorrhagic outcomes.

An investigation of germline variants of HAVCR2 in subcutaneous panniculitis-like T-cell lymphoma and related lesions in a North American population.

Not available.

The optimization of the vault-predicting formula based on the anterior segment measurements from artemis insight 100.

To optimize and evaluate the accuracy of the vault-predicting formula generated from a very high-frequency digital ultrasound robotic scanner (Artemis Insight 100). The relationship between the achieved lens vault (LVa) at one month after intraocular collamer lens (ICL) implantation surgery and the predicted vault (LVp) was analyzed by a retrospective study, and an optimized formula was built up. Then, the accuracy of the optimized vault-predicting formula was evaluated in a prospective study by comparing the LVa and the predicted vault from the optimized formula (LVop). The retrospective study included 77 patients (133 eyes) while the prospective study enrolled 90 patients (170 eyes). The difference between LVp and LVa at one month after surgery was statistically significant (P < 0.05), and the linear regression analysis of LVa against LVp yielded a good fit (R2 = 0.68). The optimized vault-predicting formula was LVop (µm) = 1.21 × LVp (µm) + 124.73. In the validation study, the difference between LVop and LVa was not statistically significant (P = 0.10), and a good agreement between LVop and LVa was shown by Bland-Altman analysis. The optimized vault-predicting formula could predict the actual LV after ICL implantation surgery, help to select an appropriate ICL size and reduce the need for re-operation.

Experimental study on fractal dimension of energy dissipation and crack growth in saturated tuff at different strain rates.

In order to investigate the effects of strain rate and water saturation on the energy dissipation and crack growth of tuff, uniaxial compression tests were carried out on dry and water saturated tuff with different strain rates using an electro-hydraulic servo press and a 50 mm diameter split Hopkinson pressure rod (SHPB) device. High-speed camera and Image J image analysis software were used to obtain the crack growth process of the specimen under impact load, and fractal dimension was introduced to quantitatively study the crack growth degree. The results show that more than 90% of the energy is stored in the specimen as elastic energy when it reaches the peak stress under static load. The average total energy of water-saturated specimens is 67.55% of that of dry specimens. The average energy dissipation density of water-saturated specimens under 0.3 MPa, 0.4 MPa and 0.5 MPa air pressure is 0.79, 0.91 and 0.92 times of that of dry specimens, respectively. Water-saturated specimens will deteriorate and thus reduce their energy storage and energy absorption effects. The reflected energy, transmitted energy, absorbed energy and incident energy are linear, logarithmic and linear functions, respectively, and the energy absorptivity and specific energy absorptivity of water-saturated specimens are lower than those of dry specimens. Due to the existence of "stefan" effect, the increase of energy dissipation density of water-saturated specimen at high strain rate is greater than that of dry specimen. The mean fractal dimension of water-saturated specimens under 0.3 MPa, 0.4 MPa and 0.5 MPa is 1.09, 1.05 and 1.16 times that of dry specimens. At the same strain rate, the number and width of cracks in water-saturated specimens are larger than that in dry specimens. Water-saturated behavior reduces the energy absorption capacity of tuff, increases the fractal dimension of crack growth, and significantly reduces the resistance of water-saturated rock to external loads.

PURPL Promotes M2 Macrophage Polarization in Lung Cancer by Regulating RBM4/xCT Signaling.

Lung cancer is the most common malignancy worldwide. Long non-coding RNA (lncRNA) p53 upregulated regulator of P53 levels (PURPL) is abnormally in various cancers. However, the reports on its roles in lung cancer are limited. The purpose of present study is to investigate the potentials of lncRNA PURPL in lung cancer. PURPL and mRNA expression was determined using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). The location of PURPL was detected using RNA fluorescence in situ hybridization (FISH) assay. Protein expression was detected using western blot. Cellular functions were determined using flow cytometry. The interaction between PURPL and RNA-binding motif 4 (RBM4) was confirmed using RNA immunoprecipitation (RIP) assay. PURPL was overexpressed in lung cancer cells and patients. Overexpressed PURPL promoted M2 macrophage polarization and suppressed ferroptosis. Additionally, PURPL maintained the mRNA stability of cystine glutamate reverse transporter (xCT) via regulating RBM4. xCT knockdown antagonized the effects of overexpressed PURPL and inhibited M2 macrophage polarization via inducing macrophage ferroptosis. PURPL/RBM4/xCT axis promoted M2 macrophage polarization in lung cancer. Therefore, PURPL may be a potential target of lung cancer.

Combinations of Energy-based Devices plus isotretinoin for management of acne and acne scars: A systematic review.

BACKGROUND AND OBJECTIVE: A 6-month interval between systemic isotretinoin (ISO) and the initiation of energy-based interventions has been recommended, due to concerns about keloid formation and delayed wound healing. While this postponement goes against the current trend of early intervention for acne scarring. This systematic review evaluates the efficacy, safety, and patient satisfaction of combinations of ISO with energy-based devices (EBD). STUDY DESIGN/METHODS AND MATERIALS: PubMed, Embase, Web of Science, Cochrane Library, and Cochrane Central Register of Controlled Trials were comprehensively searched up to April 2023 according to PRISMA guidelines. Two independent reviewers screened the titles and abstracts to select articles. The quality of the literature was assessed for each study design. RESULTS: A total of 16 studies addressing the efficacy and safety of energy-based modalities combined with ISO were identified, including six randomized controlled trials (RCTs), two case series, seven cohort studies, and one case report. ISO combinations with intense pulsed light (IPL), fractional ablative CO2 laser, pulsed dye laser (PDL), non-ablative fractional laser (NAFL) and fractional microneedle radiofrequency (FMRF) have been tested for improving acne severity, acne scarring and erythema. CONCLUSION: The current evidence does not justify delaying the use of EBDs for patients who have recently undergone or are currently receiving ISO treatment. Evidence-based treatments such as PDL, NAFL, and FMRF etc. are suggested relatively safe and effective in treating acne and acne scarring.

Single-cell and Bulk Transcriptomic Analyses Reveal a Stemness and Circadian Rhythm Disturbance-related Signature Predicting Clinical Outcome and Immunotherapy Response in Hepatocellular Carcinoma.

AIMS: Investigating the impact of stemness-related circadian rhythm disruption (SCRD) on hepatocellular carcinoma (HCC) prognosis and its potential as a predictor for immunotherapy response. BACKGROUND: Circadian disruption has been linked to tumor progression through its effect on the stemness of cancer cells. OBJECTIVE: Develop a novel signature for SCRD to accurately predict clinical outcomes and immune therapy response in patients with HCC. METHODS: The stemness degree of patients with HCC was assessed based on the stemness index (mRNAsi). The co-expression circadian genes significantly correlated with mRNAsi were identified and defined as stemness- and circadian-related genes (SCRGs). The SCRD scores of samples and cells were calculated based on the SCRGs. Differentially expressed genes with a prognostic value between distinct SCRD groups were identified in bulk and single-cell datasets to develop an SCRD signature. RESULTS: A higher SCRD score indicates a worse patient survival rate. Analysis of the tumor microenvironment revealed a significant correlation between SCRD and infiltrating immune cells. Heterogeneous expression patterns, functional states, genomic variants, and cell-cell interactions between two SCRD populations were revealed by transcriptomic, genomic, and interaction analyses. The robust SCRD signature for predicting immunotherapy response and prognosis in patients with HCC was developed and validated in multiple independent cohorts. CONCLUSIONS: In summary, distinct tumor immune microenvironment patterns were confirmed under SCRD in bulk and single-cell transcriptomic, and SCRD signature associated with clinical outcomes and immunotherapy response was developed and validated in HCC.