Clinical and laboratory features between anti-TIF1γ dermatomyositis with and without malignancy: 37 case series and a review.

We aimed to analyze the clinical profile and malignancy indicators in dermatomyositis (DM) with anti-transcriptional intermediary factor 1 antibody (anti-TIF1γ-Ab). A comparison was made between clinical information of anti-TIF1γ DM patients with and without malignancy. Additionally, a review of the literature on anti-TIF1γ DM and malignancy was conducted by searching PubMed and EMBASE databases. In our cohort of 37 patients, 27.0% (10/37) developed malignancy. The timeframe during which these 10 patients developed malignancy ranged from 21 months prior to the diagnosis of DM to 36 months following the diagnosis of DM. Specifically, one patient was diagnosed with breast cancer at the age of 36. Comparing the groups with and without malignancy, we found that age over 65 years (40% vs 7.4%, P = 0.035), a shorter duration from the onset of symptoms to the diagnosis of DM (2.5 vs 10 months, P = 0.003), and higher erythrocyte sedimentation rate (ESR) levels (23 vs 10 mm/h, P = 0.048) were found to be associated with an increased risk of malignancy. Conversely, the presence of Gottron's papules (63% vs 20%, P = 0.029) may suggest a lower likelihood of malignancy. The literature review revealed that the prevalence of myositis-associated malignancy was 40.7% (340/836), with variations ranging from 19% to 82.9% across different series. In summary, factors such as age over 65 years, a shorter duration between symptom onset and diagnosis of DM, and elevated ESR levels may indicate an increased risk of malignancy in anti-TIF1γ DM patients.

The superiority of isomeric, fluorination and curtailed π-conjunction on A-D-A type acceptors for organic photovoltaics.

The performance of organic solar cell (OSC) devices has been significantly enhanced by the dramatic evolution of A-D-A type non-fullerene acceptors (NFAs). Nevertheless, the structure-property-performance relationship of NFAs in the OSC device is unclear. Here, the intrinsic design factors of isomeric, fluorination and π-conjunction curtailing on the photophysical properties of benzodi (thienopyran) (BDTP) (named NBDTP-M, NBDTTP-M, NBDTP-Fin, and NBDTP-Fout)-based NFAs are discussed. The results show that fluorination on the terminal group of NBDTP-Fout could effectively decrease the highest occupied orbital (HOMO) energy level and the lowest unoccupied orbital (LUMO) energy level. And the long π-conjugated donor unit for NBDTTP-M could increase the HOMO energy level and bring a small HOMO-LUMO energy bandgap. Meanwhile, the substitution of external oxygen atoms and the fluorine atoms in the terminal group could introduce positive changes to the electrostatic potential of the NBDTP-Fout, favouring the charge separation at the donor/acceptor interface. Moreover, the structural design of external oxygen atom substitution, fluorination on the terminal group and curtailed π-conjugated donor unit could decrease the electron vibration-coupling of exciton diffusion, exciton dissociation and electronic transfer processes. The suppression of the exciton decay and charge recombination in those high-performance NFAs indicate that the investigated molecular designs could be effective for further improvement of OSCs.

Enhancing the potential application of food-waste biochar as a sustainable bio-solid fuel: Analysis of post-treatment and combustion behavior.

Food-waste biochar holds significant potential as a bio-solid fuel for achieving carbon neutrality; however, its high content of sodium (Na), potassium (K), calcium (Ca), chlorine (Cl), and nitrogen, inhibits its potential use. This study explored the effects of post-treatment with ascorbic, acetic, citric, and iminodiacetic acids on the properties of food-waste biochar and volatile ionic substances to establish a foundation for assessing both the environmental impact and practical use of food waste. Post-treatment with organic acids achieved 92% Cl-removal efficiency and induced deformation of the functional groups of food-waste biochar surfaces, leading to the re-adsorption of alkali and alkaline earth metals. This re-adsorption of alkali metal ions showed a distinct correlation with NOx mitigation. The amount of re-adsorbed Na and K varied based on the types of organic acids, resulting in different NOx emission reduction effects. Iminodiacetic acid was particularly effective in alleviating Ca and PO4 volatilization, whereas citric acid exhibited the highest Ca elution performance, and the Ca-contained leachate is a potential source of CO2 storage through indirect mineral carbonation. Acetic acid is the most feasible alternative, considering both economic and environmental aspects. The findings suggest that the post-treatment of food-waste biochar effectively mitigates air pollutants during combustion and is beneficial for sustainable biosolid fuel production and bio-waste management.

Ligustrazine alleviates spinal cord injury-induced neuropathic pain by inhibiting the TLR4/NF-κB signaling pathway.

OBJECTIVE: To investigate the effects of ligustrazine on neuropathic pain (NPP) in rats with sciatic nerve injury and to provide new scientific insight for broadening the clinical application of ligustrazine. METHODS: Human spinal cord cell line STR cells were transfected with TLR4-mimic or mimic negative control (mimic-NC). After transfection, the STR cells were treated with different concentrations of ligustrazine (0, 0.25, 0.5, 1, 2 µm) for 24 h or 48 h. Cell proliferation was detected by MTT assay and colony formation assay. A rat model was further constructed to evaluate mechanical and cold pain sensitivity behaviors by fiber mechanical stimulation and freezing spray. The extracellular fluids of medial prefrontal cortex (mPFC) and central amygdala (CeA) were collected by intracranial dual-site simultaneous microdialysis. The contents of glutamic acid (Glu), aspartate (Asp), glycine (Gly), and γ-aminobutyric acid (GABA) in extracellular fluids were detected by HPLC. RESULTS: Compared to the 0 µm group, ligustrazine concentration at 0.5 µm significantly decreased the relative cell viability of STR cells and promoted the cell apoptosis rate. Ligustrazine at 0.25 µm significantly reduced the colony number of STR cells (all P<0.05). Compared to the control group, 1 µM ligustrazine significantly increased the protein expression of Bax and cleaved caspase 3 in STR cells but decreased the protein expression of Bcl-2 (all P<0.001). Compared to the control group, 2 µM ligustrazine treatments significantly reduced the protein levels of TLR4 and p-Akt in STR cells (all P<0.001). However, 2 µM ligustrazine treatments did not change the protein expression of Akt (P>0.05). Compared to the control group, the level of TLR4 in STR cells transfected with TLR4-mimic was significantly increased (P<0.001). Compared to the control group, transfection of TLR4-mimic reversed the anti-proliferative and pro-apoptotic effects of ligustrazine on STR cells (all P<0.001). CONCLUSION: The analgesic effect of Ligustrazine on neuropathic pain caused by spinal cord injury may be related to its inhibition of the release of excitatory amino acid transmitters Glu and Gly through the TLR4/NF-κB pathway, regulation of the dynamic balance of excitatory and inhibitory amino acid neurotransmitters, and alleviation of the central sensitization effect caused by the excitotoxicity of Glu.

Gray matter structural alterations of cortico-striato-thalamo-cortical loop in familial Paroxysmal Kinesigenic Dyskinesia.

Background: Previous studies have indicated that patients with Paroxysmal Kinesigenic Dyskinesia (PKD) exhibit reduced gray matter volume in certain brain regions within the cortico-striato-thalamo-cortical (CSTC) loop. However, a comprehensive investigation specifically targeting the CSTC loop in PKD has never been conducted. Objectives: To provide evidence for the involvement of the CSTC loop in the pathogenesis of PKD from the perspective of structural alterations, this study carried out a surface-based morphometry (SBM), voxel-based morphometry (VBM), and structural covariance networks (SCN) combined analysis in familial PKD patients. Methods: A total of 8 familial PKD patients and 10 healthy family members were included in the study and underwent Brain MRI examinations. Based on 3D T1 MPRAGE data, neuroimaging metrics of cortical thickness from SBM, subcortical nuclei volume from VBM, and covariance coefficient from SCN were used to systematically investigate the brain structural alterations along the CSTC loop of PKD patients. Results: A significant decrease in the average cortical thickness of the left S1 region in the PKD group was observed. The volumes of subcortical nuclei, including the thalamus, putamen, and globus pallidus were reduced, with a pronounced effect observed in the bilateral putamen. And the structural covariance connection between the left putamen and the left globus pallidus was significantly strengthened. Conclusions: The study confirms the involvement of the CSTC loop in the pathogenesis of PKD from the perspective of structural alterations, and the findings may provide potential targets for objective diagnosis and therapeutic monitoring of PKD.

Strategies for adaptation to high light in plants.

Plants absorb light energy for photosynthesis via photosystem complexes in their chloroplasts. However, excess light can damage the photosystems and decrease photosynthetic output, thereby inhibiting plant growth and development. Plants have developed a series of light acclimation strategies that allow them to withstand high light. In the first line of defense against excess light, leaves and chloroplasts move away from the light and the plant accumulates compounds that filter and reflect the light. In the second line of defense, known as photoprotection, plants dissipate excess light energy through non-photochemical quenching, cyclic electron transport, photorespiration, and scavenging of excess reactive oxygen species. In the third line of defense, which occurs after photodamage, plants initiate a cycle of photosystem (mainly photosystem II) repair. In addition to being the site of photosynthesis, chloroplasts sense stress, especially light stress, and transduce the stress signal to the nucleus, where it modulates the expression of genes involved in the stress response. In this review, we discuss current progress in our understanding of the strategies and mechanisms employed by plants to withstand high light at the whole-plant, cellular, physiological, and molecular levels across the three lines of defense.

Environmental implications of migration: Worldwide insights.

This study investigates the impact of migrants' skills, employment sectors, urban planning and energy sectors efficiency on carbon emissions. Utilizing the static and dynamic methods Dynamic GMM, Spatial methods on a panel dataset covering 156 nations from 2000 to 2022. Our findings reveal that heightened geopolitical risk leads to both short and long run increases in carbon emissions and the ecological footprint. The results indicate positive impact of international migration, travel services and urbanization on CO2 emissions. The results also investigate interaction effects, revealing the amplifying effect of urban population density on the association between international migration and CO2 emissions. The disaggregated analysis shows that migrants positively impact CO2 emissions in high income, Lower Income while there is complex association in upper middle-income economies. The findings provide policymakers with valuable insights for prioritizing the adoption of renewable energy, sustainable urban planning, energy efficiency measures, sustainable tourism practices, carbon pricing mechanisms, international cooperation, and sustainable economic growth strategies that are tailored to specific country contexts.

Systematic pharmacology and experimental validation to elucidate the inflammation-associated mechanism of Huanglian Wendan (HLWD) decoction in the treatment of MAFLD associated with atherosclerosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic-associated fatty liver disease (MAFLD) and atherosclerosis are very common disorders that frequently coexist. The therapeutic efficacy of Huanglian Wendan (HLWD) decoction, a traditional Chinese medicine (TCM) prescription, is satisfactory in treating MAFLD associated with atherosclerosis. However, the underlying mechanisms through which HLWD exerts its effects need to be elucidated. Given the complex composition of HLWD and its multiple therapeutic targets, pharmacological investigation is challenging. AIM OF THIS STUDY: This study aimed to identify the effective compounds in HLWD and elucidate the mechanisms involved in its therapeutic effect on MAFLD associated with atherosclerosis. MATERIALS AND METHODS: We used a systematic pharmacology method to identify effective compounds present in HLWD and determine the mechanism by which it affects MAFLD associated with atherosclerosis. The effective components of HLWD were identified through ultrahigh-performance liquid chromatography-q exactive-orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Next, a comprehensive in silico method was used to predict potential related targets and disease targets for these compounds to establish corresponding pathways. The accuracy of our assumed systemic pharmacology results was determined by conducting follow-up experiments. RESULTS: By conducting UHPLC-Q-Orbitrap HRMS combined with network analysis, we identified 18 potentially active components of HLWD and assessed the inflammatory regulatory mechanism by which it affects MAFLD associated with atherosclerosis on the basis of 52 key targets. We used a high-fat, high-cholesterol (HFHC)-induced mice model of MAFLD associated with atherosclerosis to confirm our results. We found that administering HLWD significantly improved the appearance of their liver and reduced their body weight, liver weight, blood lipids, hepatic damage, and hepatic pathology. HLWD also decreased atherosclerotic lesion areas, foam cells, and inflammatory cells in the aorta. HLWD showed anti-inflammatory effects, suppressed M1 polarization, and promoted M2 polarization in the liver and aorta. HLWD might also regulate peroxisome proliferator-activated receptor-γ (PPARγ)/nuclear factor kappa-B (NF-κB) signaling to influence macrophage polarization and inflammation. CONCLUSIONS: Our results showed that HLWD protected against HFHC diet-induced MAFLD associated with atherosclerosis by regulating PPARγ/NF-κB signaling, thus adjusting macrophage polarization and inflammation. Additionally, pharmacochemistry research, network pharmacology analysis, and experimental verification can be combined to form a comprehensive model used in studies on TCM.

Interferon Regulatory Factor 4: An Alternative Marker for Plasma Cells in Daratumumab-Treated Patients With Multiple Myeloma.

INTRODUCTION: Anti-CD38 therapeutic modalities (e.g., daratumumab) can impede classical CD38 and CD138 gating use for plasma cell (PC) detection in multiple myeloma (MM) patients with minimal residual disease (MRD). We assessed the applicability of CD229, CD269, and interferon regulatory factor (IRF-4) for PC detection in MM MRD patients. METHODS: Bone marrow samples were collected from patients with MM. Through multiparameter flow cytometry, we evaluated the suitability of CD229, CD269, and IRF-4 for distinguishing PCs from other hematopoietic cells and compared their expression pattern on normal PCs (nPCs) and aberrant PCs (aPCs). We also assessed IRF-4 expression stability after sample storage under different conditions. A 10-color MRD antibody panel was used to determine whether IRF-4 is an alternative primary PC-gating marker for MM MRD assessment. RESULTS: IRF-4 was expressed specifically on all PCs; its mean fluorescence intensity (MFI) was highest on PCs among all hematopoietic cells. This MFI did not decrease even after sample storage at 4°C or 25°C for 72 h. In all 42 MRD assessment samples, except for samples (n = 10) with no PCs, the use of IRF-4 enabled accurate nPC (n = 12), aPC (n = 13), and nPC + aPC (n = 7) identification. Even samples from daratumumab-treated patients had high IRF-4 MFI, with no difference between pre-treatment and post-treatment (n = 7; p = 0.610). CONCLUSIONS: IRF-4 demonstrates high MFI on PCs, and it is not expressed on other leukocytes. In MM patients with MRD, daratumumab treatment does not affect IRF-4 expression. IRF-4 is a promising marker for PC identification in MRD assessment of MM patients undergoing anti-CD38 therapy.

Bioaccessibility and bioavailability of exogenous and endogenous toxic substances in traditional Chinese medicine and their significance in risk assessment.

Scientific risk assessment of exogenous and endogenous toxic substances in traditional Chinese medicine (TCM) is of great significance. The present review comprises a comprehensive summary of progress in the health risk assessment of harmful exogenous substances in TCMs. Such substances include heavy metals, pesticide residues, biotoxins, and endogenous toxic components involving pyrrolizidine alkaloids. The review also discusses the strengths and weaknesses of various bioaccessibility and bioavailability models, and their applications in risk assessment. Future avenues of risk assessment research are highlighted, including further exploration of risk assessment parameters, innovation of bioaccessibility and bioavailability techniques, enhancement of probabilistic risk assessment combined with bioavailability, improvement of cumulative risk assessment strategies, and formulation of strategies for reducing relative bioavailability (RBA) values in TCMs. Such efforts represent an attempt to develop a risk assessment system that is capable of evaluating the exogenous and endogenous toxic substances in TCMs to ensure its safe use in clinics, and to promote the sustainable development of the TCM industry.

Joint trajectory inference for single-cell genomics using deep learning with a mixture prior.

Trajectory inference methods are essential for analyzing the developmental paths of cells in single-cell sequencing datasets. It provides insights into cellular differentiation, transitions, and lineage hierarchies, helping unravel the dynamic processes underlying development and disease progression. However, many existing tools lack a coherent statistical model and reliable uncertainty quantification, limiting their utility and robustness. In this paper, we introduce VITAE (Variational Inference for Trajectory by AutoEncoder), a statistical approach that integrates a latent hierarchical mixture model with variational autoencoders to infer trajectories. The statistical hierarchical model enhances the interpretability of our framework, while the posterior approximations generated by our variational autoencoder ensure computational efficiency and provide uncertainty quantification of cell projections along trajectories. Specifically, VITAE enables simultaneous trajectory inference and data integration, improving the accuracy of learning a joint trajectory structure in the presence of biological and technical heterogeneity across datasets. We show that VITAE outperforms other state-of-the-art trajectory inference methods on both real and synthetic data under various trajectory topologies. Furthermore, we apply VITAE to jointly analyze three distinct single-cell RNA sequencing datasets of the mouse neocortex, unveiling comprehensive developmental lineages of projection neurons. VITAE effectively reduces batch effects within and across datasets and uncovers finer structures that might be overlooked in individual datasets. Additionally, we showcase VITAE's efficacy in integrative analyses of multiomic datasets with continuous cell population structures.

Comparison of metastasectomy and stereotactic body radiation therapy for pulmonary oligometastasis from hepatocellular carcinoma: a propensity score-weighted analysis.

PURPOSE: While there is a growing role for local therapy in patients with hepatocellular carcinoma (HCC) and pulmonary oligometastasis, it remains unclear whether metastatectomy or stereotactic body radiation therapy (SBRT) is the more effective treatment for these patients. We aimed to compare the oncologic outcomes of metastasectomy and SBRT for HCC with pulmonary oligometastasis. METHODS: We retrospectively analyzed 209 HCC patients with 322 metastatic lung lesions who underwent either metastasectomy (150 patients with 241 lesions) or SBRT (59 patients with 81 lesions) between January 2008 and December 2018. Propensity score-based inverse probability of treatment weighting (IPTW) was used to minimize potential bias between the two groups. RESULTS: The median follow-up duration was 39.8 months (range, 2.3-166.9). The 2-year rate of freedom from local progression (FFLP) was 98.2% in the metastasectomy group and 97.0% in the SBRT group (p = 0.197). The 2-year rates of overt systemic progression-free survival (ovPFS, 51.0% vs. 46.1%; p = 0.274), progression-free survival (PFS, 26.3% vs. 9.1%; p = 0.074), and overall survival (OS, 74.0% vs. 57.6%; p = 0.006) were higher in the metastasectomy group. After IPTW adjustment, the 2-year rates of ovPFS (50.8% vs. 52.7%; p = 0.396), PFS (23.0% vs. 24.7%; p = 0.478), and OS (72.6% vs. 83.0%, p = 0.428) were not significantly different between the two groups. In multivariate analysis, viable intrahepatic lesions and the number of prior liver-directed therapies were found to be significant prognostic factors for OS and PFS. The time interval between HCC diagnosis and the development of pulmonary metastases was also significantly associated with OS. CONCLUSIONS: Both metastasectomy and SBRT demonstrated excellent local control and comparable oncologic outcomes in patients with pulmonary oligometastasis from HCC. The treatment modality for these patients could be determined based on the individual patient's condition and intrahepatic disease status.

Resveratrol Alleviated T-2 Toxin-Induced Liver Injury via Preservation of Nrf2 Pathway and GSH Synthesis.

T-2 toxin is a trichothecene mycotoxin and is considered as an extremely inevitable pollutant with potent hepatotoxicity. However, the approach to alleviation of T-2 toxin-triggered hepatotoxicity has been recognized as a serious challenge. Resveratrol (Res) is a polyphenol natural product isolated from various plant species, but its protective effect against T-2 toxin hepatotoxicity and detailed mechanism remains obscure. In the present study, the effect of Res against the hepatotoxicity was evaluated, and the underlying mechanisms were further revealed in mice. Functionally, Res inhibited liver injury, oxidative damage, and mitochondrial dysfunction induced by T-2 toxin. Mechanistically, Res modulated Nrf2-mediated antioxidant pathway and glutathione synthesis inhibition. Collectively, our findings first showed beyond doubt that Res ameliorated T-2 toxin-triggered liver injury by regulating Nrf2 pathways in mice.

The application of real-time indocyanine green fluorescence cholangiography in laparoscopic living donor left lateral sectionectomy.

Background: The judgment of the division point of the bile duct has always been one of the difficulties of laparoscopic left lateral sectionectomy (LLLS). The purpose of this study was to assess the effects of indocyanine green (ICG) fluorescence cholangiography during LLLS on the occurrence of biliary complications in both donors and recipients. The optimal dose and injection time of ICG were also investigated. Methods: This is a retrospective cohort study. From October 2016 to December 2022, the clinical data of 103 donors who underwent LLLS and relevant recipients were retrospectively analyzed. According to whether ICG fluorescence cholangiography was used, they were divided into a non-ICG group (n=46) and an ICG group (n=57). Biliary complications were observed and the optimal dose and injection time of ICG were explored. Results: Three donors in the non-ICG group suffered from bile leakage. Four grafts had multiple bile duct openings and biliary complications were observed in the relevant recipients who received these grafts in the non-ICG group. Two recipients had bile leakage, and the other two had biliary stenosis. There was no biliary complications both in donors and recipients in the ICG group. The fluorescence intensity of the liver was 108.1±17.6 at a dose of 0.004 mg/kg 90 minutes after injection, significantly weaker than that at 0.05 mg/kg 30 minutes (200.3±17.6, P=0.001) and 90 minutes after injection (140.2±15.4, P=0.001). The fluorescence intensity contrast value at a dose of 0.004 mg/kg was stronger than that at 0.05 mg/kg, both measured 90 minutes after injection (0.098±0.032 vs. 0.078±0.022, P=0.021). Conclusions: ICG fluorescence cholangiography is safe and feasible in LLLS. It reduces biliary complications in both donors and recipients. The optimal ICG dose was 0.004 mg/kg, and 90 minutes after injection was the best observation time. ICG fluorescence cholangiography is recommended for routine use in LLLS.

Excimer-ultraviolet-lamp-assisted selective etching of single-layer graphene and its application in edge-contact devices.

Since the discovery of graphene and its remarkable properties, researchers have actively explored advanced graphene-patterning technologies. While the etching process is pivotal in shaping graphene channels, existing etching techniques have limitations such as low speed, high cost, residue contamination, and rough edges. Therefore, the development of facile and efficient etching methods is necessary. This study entailed the development of a novel technique for patterning graphene through dry etching, utilizing selective photochemical reactions precisely targeted at single-layer graphene (SLG) surfaces. This process is facilitated by an excimer ultraviolet lamp emitting light at a wavelength of 172 nm. The effectiveness of this technique in selectively removing SLG over large areas, leaving the few-layer graphene intact and clean, was confirmed by various spectroscopic analyses. Furthermore, we explored the application of this technique to device fabrication, revealing its potential to enhance the electrical properties of SLG-based devices. One-dimensional (1D) edge contacts fabricated using this method not only exhibited enhanced electrical transport characteristics compared to two-dimensional contact devices but also demonstrated enhanced efficiency in fabricating conventional 1D-contacted devices. This study addresses the demand for advanced technologies suitable for next-generation graphene devices, providing a promising and versatile graphene-patterning approach with broad applicability and high efficiency.

Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients.

OBJECTIVE: The activities and products of carbohydrate metabolism are involved in key processes of cancer. However, its relationship with hepatocellular carcinoma (HCC) is unclear. METHODS: The cancer genome atlas (TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases. Differentially expressed genes (DEGs) between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes (CRGs) to obtain differentially expressed CRGs (DE-CRGs). Then, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were applied to identify risk model genes, and HCC samples were divided into high/low-risk groups according to the median risk score. Next, gene set enrichment analysis (GSEA) was performed on the risk model genes. The sensitivity of the risk model to immunotherapy and chemotherapy was also explored. RESULTS: A total of 8 risk model genes, namely, G6PD, PFKFB4, ACAT1, ALDH2, ACYP1, OGDHL, ACADS, and TKTL1, were identified. Moreover, the risk score, cancer status, age, and pathologic T stage were strongly associated with the prognosis of HCC patients. Both the stromal score and immune score had significant negative/positive correlations with the risk score, reflecting the important role of the risk model in immunotherapy sensitivity. Furthermore, the stromal and immune scores had significant negative/positive correlations with risk scores, reflecting the important role of the risk model in immunotherapy sensitivity. Eventually, we found that high-/low-risk patients were more sensitive to 102 drugs, suggesting that the risk model exhibited sensitivity to chemotherapy drugs. The results of the experiments in HCC tissue samples validated the expression of the risk model genes. CONCLUSION: Through bioinformatic analysis, we constructed a carbohydrate metabolism-related risk model for HCC, contributing to the prognosis prediction and treatment of HCC patients.

PIEZO1 targeting in macrophages boosts phagocytic activity and foam cell apoptosis in atherosclerosis.

The rising incidences of atherosclerosis have necessitated efforts to identify novel targets for therapeutic interventions. In the present study, we observed increased expression of the mechanosensitive calcium channel Piezo1 transcript in mouse and human atherosclerotic plaques, correlating with infiltration of PIEZO1-expressing macrophages. In vitro administration of Yoda1, a specific agonist for PIEZO1, led to increased foam cell apoptosis and enhanced phagocytosis by macrophages. Mechanistically, PIEZO1 activation resulted in intracellular F-actin rearrangement, elevated mitochondrial ROS levels and induction of mitochondrial fragmentation upon PIEZO1 activation, as well as increased expression of anti-inflammatory genes. In vivo, ApoE-/- mice treated with Yoda1 exhibited regression of atherosclerosis, enhanced stability of advanced lesions, reduced plaque size and necrotic core, increased collagen content, and reduced expression levels of inflammatory markers. Our findings propose PIEZO1 as a novel and potential therapeutic target in atherosclerosis.

Checkpoint for Considering Interleukin-6 as a Potential Target to Mitigate Secondary Brain Injury after Cardiac Arrest.

Interleukin-6 (IL-6) was suggested as a potential target for intervention to mitigate brain injury. However, its neuro-protective effect in post-resuscitation care has not been proven. We investigated the time-course of changes in IL-6 and its association with other markers (systemic inflammation and myocardial and neuronal injury), according to the injury severity of the cardiac arrest. This retrospective study analyzed IL-6 and other markers at baseline and 24, 48, and 72 h after the return of spontaneous circulation. The primary outcome was the association of IL-6 with injury severity as assessed using the revised Post-Cardiac Arrest Syndrome for Therapeutic Hypothermia scoring system (low, moderate, and high severity). Of 111 patients, 22 (19.8%), 61 (55.0%), and 28 (25.2%) had low-, moderate-, and high-severity scores, respectively. IL-6 levels were significantly lower in the low-severity group than in the moderate- and high-severity groups at baseline and at 24 h and 72 h (p < 0.005). While IL-6 was not independently associated with neuronal injury markers in the low-severity group, it was demonstrated to be associated with it in the moderate-severity (ß [95% CI] = 4.3 [0.1-8.6], R2 = 0.11) and high-severity (ß [95% CI] = 7.9 [3.4-12.5], R2 = 0.14) groups. IL-6 exhibits distinct patterns across severity and shows differential associations with systemic inflammation or neuronal injury.