Quantification of infarct core volume in patients with acute ischemic stroke using cerebral metabolic rate of oxygen (CMRO2) in CT perfusion.

BACKGROUND AND PURPOSE: The cerebral metabolic rate of oxygen (CMRO2) is considered a robust marker of the infarct core in 15°-tracer- based positron emission tomography. We aimed to delineate the infarct core in patients with acute ischemic stroke using commonly used relative cerebral blood flow (rCBF) < 30% and oxygen metabolism parameter of CMRO2 on CT perfusion in comparison with pre-treatment diffusion- weighted imaging (DWI)-derived infarct core volume. MATERIALS AND METHODS: Patients with acute ischemic stroke who met the inclusion criteria were recruited. The CMRO2 and CBF maps in CT perfusion were automatically generated using post-processing software. The infarct core volume was quantified with relative (r) CMRO2 < 20% - 30% and rCBF < 30%. The optimal threshold was defined as those that demonstrated the smallest mean absolute error, lowest mean infarct core volume difference, narrowest 95% limit of agreement, and largest intraclass correlation coefficient (ICC) against the DWI. RESULTS: This study included 76 patients (mean age ± standard deviation, 69.97 ± 12.15 years, 43 males). The optimal thresholds of rCMRO2 < 26% resulted in the lowest mean infarct core volume difference, narrowest 95% limit of agreement, and largest ICC among different thresholds. Bland-Altman analysis demonstrated a volumetric bias of 1.96 mL between DWI and rCMRO2 < 26%, whereas in cases of DWI and rCBF < 30%, the bias was notably larger at 14.10 mL. The highest correlation was observed for rCMRO2 < 26% (ICC=0.936), whereas rCBF < 30% showed a slightly lower ICC of 0.934. CONCLUSIONS: CT perfusion-derived CMRO2 is a promising parameter for estimating the infarct core volume in patients with acute ischemic stroke. ABBREVIATIONS: CMRO2 = cerebral metabolic rate of oxygen.

Establishment of canine mammary gland tumor cell lines harboring PI3K/Akt activation as a therapeutic target.

Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.

ac4C-AFL: A high-precision identification of human mRNA N4-acetylcytidine sites based on adaptive feature representation learning.

RNA N4-acetylcytidine (ac4C) is a highly conserved RNA modification that plays a crucial role in controlling mRNA stability, processing, and translation. Consequently, accurate identification of ac4C sites across the genome is critical for understanding gene expression regulation mechanisms. In this study, we have developed ac4C-AFL, a bioinformatics tool that precisely identifies ac4C sites from primary RNA sequences. In ac4C-AFL, we identified the optimal sequence length for model building and implemented an adaptive feature representation strategy that is capable of extracting the most representative features from RNA. To identify the most relevant features, we proposed a novel ensemble feature importance scoring strategy to rank features effectively. We then used this information to conduct the sequential forward search, which individually determine the optimal feature set from the 16 sequence-derived feature descriptors. Utilizing these optimal feature descriptors, we constructed 176 baseline models using 11 popular classifiers. The most efficient baseline models were identified using the two-step feature selection approach, whose predicted scores were integrated and trained with the appropriate classifier to develop the final prediction model. Our rigorous cross-validations and independent tests demonstrate that ac4C-AFL surpasses contemporary tools in predicting ac4C sites. Moreover, we have developed a publicly accessible web server at https://balalab-skku.org/ac4C-AFL/.

MiR-29 and MiR-140 regulate TRAIL-induced drug tolerance in lung cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has chemotherapeutic potential as a regulator of an extrinsic apoptotic ligand, but its effect as a drug is limited by innate and acquired resistance. Recent findings suggest that an intermediate drug tolerance could mediate acquired resistance, which has made the main obstacle for limited utility of TRAIL as an anti-cancer therapeutics. We propose miRNA-dependent epigenetic modification drives the drug tolerant state in TRAIL-induced drug tolerant (TDT). Transcriptomic analysis revealed miR-29 target gene activation in TDT cells, showing oncogenic signature in lung cancer. Also, the restored TRAIL-sensitivity was associated with miR-29ac and 140-5p expressions, which is known as tumor suppressor by suppressing oncogenic protein RSK2 (p90 ribosomal S6 kinase), further confirmed in patient samples. Moreover, we extended this finding into 119 lung cancer cell lines from public data set, suggesting a significant correlation between TRAIL-sensitivity and RSK2 mRNA expression. Finally, we found that increased RSK2 mRNA is responsible for NF-κB activation, which we previously showed as a key determinant in both innate and acquired TRAIL-resistance. Our findings support further investigation of miR-29ac and -140-5p inhibition to maintain TRAIL-sensitivity and improve the durability of response to TRAIL in lung cancer.

Modeling acute myocardial infarction and cardiac fibrosis using human induced pluripotent stem cell-derived multi-cellular heart organoids.

Heart disease involves irreversible myocardial injury that leads to high morbidity and mortality rates. Numerous cell-based cardiac in vitro models have been proposed as complementary approaches to non-clinical animal research. However, most of these approaches struggle to accurately replicate adult human heart conditions, such as myocardial infarction and ventricular remodeling pathology. The intricate interplay between various cell types within the adult heart, including cardiomyocytes, fibroblasts, and endothelial cells, contributes to the complexity of most heart diseases. Consequently, the mechanisms behind heart disease induction cannot be attributed to a single-cell type. Thus, the use of multi-cellular models becomes essential for creating clinically relevant in vitro cell models. This study focuses on generating self-organizing heart organoids (HOs) using human-induced pluripotent stem cells (hiPSCs). These organoids consist of cardiomyocytes, fibroblasts, and endothelial cells, mimicking the cellular composition of the human heart. The multi-cellular composition of HOs was confirmed through various techniques, including immunohistochemistry, flow cytometry, q-PCR, and single-cell RNA sequencing. Subsequently, HOs were subjected to hypoxia-induced ischemia and ischemia-reperfusion (IR) injuries within controlled culture conditions. The resulting phenotypes resembled those of acute myocardial infarction (AMI), characterized by cardiac cell death, biomarker secretion, functional deficits, alterations in calcium ion handling, and changes in beating properties. Additionally, the HOs subjected to IR efficiently exhibited cardiac fibrosis, displaying collagen deposition, disrupted calcium ion handling, and electrophysiological anomalies that emulate heart disease. These findings hold significant implications for the advancement of in vivo-like 3D heart and disease modeling. These disease models present a promising alternative to animal experimentation for studying cardiac diseases, and they also serve as a platform for drug screening to identify potential therapeutic targets.

Age-Related Characteristics of Resting-State Electroencephalographic Signals and the Corresponding Analytic Approaches: A Review.

The study of the effects of aging on neural activity in the human brain has attracted considerable attention in neurophysiological, neuropsychiatric, and neurocognitive research, as it is directly linked to an understanding of the neural mechanisms underlying the disruption of the brain structures and functions that lead to age-related pathological disorders. Electroencephalographic (EEG) signals recorded during resting-state conditions have been widely used because of the significant advantage of non-invasive signal acquisition with higher temporal resolution. These advantages include the capability of a variety of linear and nonlinear signal analyses and state-of-the-art machine-learning and deep-learning techniques. Advances in artificial intelligence (AI) can not only reveal the neural mechanisms underlying aging but also enable the assessment of brain age reliably by means of the age-related characteristics of EEG signals. This paper reviews the literature on the age-related features, available analytic methods, large-scale resting-state EEG databases, interpretations of the resulting findings, and recent advances in age-related AI models.

Humidity-tolerant porous polymer coating for passive daytime radiative cooling.

Coating building envelopes with a passive daytime radiative cooling (PDRC) material has attracted enormous attention as an alternative cooling technique with minimal energy consumption and carbon footprint. Despite the exceptional performance and scalability of porous polymer coating (PPC), achieving consistent performance over a wide range of drying environments remains a major challenge for its commercialization as a radiative cooling paint. Herein, we demonstrate the humidity vulnerability of PPC during the drying process and propose a simple strategy to greatly mitigate the issue. Specifically, we find that the solar reflectance of the PPC rapidly decreases with increasing humidity from 30% RH, and the PPC completely losses its PDRC ability at 45% RH and even become a solar-heating material at higher humidity. However, by adding a small amount of polymer reinforcement to the PPC, it maintains its PDRC performance up to 60% RH, resulting in a 950% increase in estimated areal coverage compared to PPC in the United States. This study sheds light on a crucial consistency issue that has thus far been rarely addressed, and offers engineering guidance to handle this fundamental threat to the development of dependable PDRC paint for industrial applications.

Data Resource Profile: The Cancer Public Library Database in South Korea.

This paper provides a comprehensive overview of the Cancer Public Library Database (CPLD), established under the Korean Clinical Data Utilization for Research Excellence project (K-CURE). The CPLD links data from four major population-based public sources: the Korea National Cancer Incidence Database in the Korea Central Cancer Registry, cause-of-death data in Statistics Korea, the National Health Information Database in the National Health Insurance Service, and the National Health Insurance Research Database in the Health Insurance Review & Assessment Service. These databases are linked using an encrypted resident registration number. The CPLD, established in 2022 and updated annually, comprises 1,983,499 men and women newly diagnosed with cancer between 2012 and 2019. It contains data on cancer registration and death, demographics, medical claims, general health checkups, and national cancer screening. The most common cancers among men in the CPLD were stomach (16.1%), lung (14.0%), colorectal (13.3%), prostate (9.6%), and liver (9.3%) cancers. The most common cancers among women were thyroid (20.4%), breast (16.6%), colorectal (9.0%), stomach (7.8%), and lung (6.2%) cancers. Among them, 571,285 died between 2012 and 2020 owing to cancer (89.2%) or other causes (10.8%). Upon approval, the CPLD is accessible to researchers through the K-CURE portal. The CPLD is a unique resource for diverse cancer research to investigate medical use before a cancer diagnosis, during initial diagnosis and treatment, and long-term follow-up. This offers expanded insight into healthcare delivery across the cancer continuum, from screening to end-of-life care.

Sports-related fractures in the geriatric population at a level I trauma center.

BACKGROUND: The population is rapidly aging and remains active over the age of 65 years. An increasing number of sports-related fractures (SRFs) in individuals 65 and older are thus anticipated. Despite the increase in SRFs among the geriatric population, there are limited studies regarding the epidemiological data regarding SRFs in geriatric patients. This study examined the epidemiology of SRFs in a geriatric population who visited a level I trauma center. METHODS: Data from geriatric patients who visited a level I trauma center were collected between June 2020 and July 2023. Overall, 1,109 geriatric patients with fractures were included in the study. Among them, 144 (13.0%) had fractures during sports activities (SRF group) and 965 (87.0%) had fractures during non-sports activities (non-SRF group). We investigated the type of sport in the SRFs and compared SRFs and NSRFs to describe the differences in patient, fracture, and treatment characteristics. RESULTS: The mean age of SRFs was significantly lower (73.6 vs. 78.7 years; P < .001). The proportion of men was significantly higher in the SRF group than in the non-SRF group (51.4 vs. 29.6%; P < .001). We identified 13 types of sports associated with fractures, and the four most common were outdoor walking (36.1%), outdoor biking (27.8%), mountain hiking (19.4%), and gym (8.3%). There were no significant differences in the rate of hospitalization, operative treatment, or length of hospital stay between the two groups. However, compared to the non-SRF group, patients in the SRF group tended to return home after hospitalization (P = .002). CONCLUSION: This epidemiological study describes geriatric population that continues to be involved in sports and is thus susceptible to fractures. The identification of the type and distribution of SRFs in geriatric patients provides useful information for determining risk factors and appropriate preventive measures that may reduce their incidence.

Multivariate Analysis of Biochemical Properties Reveals Diversity among Yardlong Beans of Different Origins.

This study analyzed the nutrient levels, secondary metabolite contents, and antioxidant activities of 35 yardlong bean accessions from China, Korea, Myanmar, and Thailand, along with their key agronomic traits. Significant variations were found in all the parameters analyzed (p < 0.05). The crude fiber (CFC), dietary fiber (DFC), total protein, and total fat contents varied from 4.10 to 6.51%, 16.71 to 23.49%, 22.45 to 28.11%, and 0.59 to 2.00%, respectively. HPLC analysis showed more than a 10-fold difference in vitamin C level (0.23 to 3.04 mg/g), whereas GC-FID analysis revealed the dominance of palmitic acid and linoleic acid. All accessions had high levels of total unsaturated fatty acids, which could help in preventing cardiovascular disease. Furthermore, total phenolic, tannin, and saponin contents ranged between 3.78 and 9.13 mg GAE/g, 31.20 and 778.34 mg CE/g, and 25.79 and 82.55 mg DE/g, respectively. Antioxidant activities like DPPH• scavenging, ABTS•+ scavenging, and reducing power (RP) ranged between 1.63 and 9.95 mg AAE/g, 6.51 and 21.21 mg TE/g, and 2.02, and 15.58 mg AAE/g, respectively. Days to flowering, total fat, palmitic acid, oleic acid, and TPC were significantly influenced by origin and genotype differences, while seeds per pod, one-hundred seeds weight, CFC, DFC, vitamin C, RP, and TSC were not affected by these factors. Multivariate analysis categorized the accessions into four clusters showing significant variations in most of the analyzed parameters. Correlation analysis also revealed significant relationships between several noteworthy parameters. Overall, this comprehensive analysis of biochemical factors revealed diversity among the different yardlong bean varieties. These findings could have practical applications in industries, breeding programs, and conservation efforts.

Identification and characterization of recent retrovirus in Rhinolophus ferrumequinum bats.

An investigation into retrovirus was conducted in six species of bats (Myotis aurascens, Myotis petax, Myotis macrodactylus, Miniopterus fuliginosus, Rhinolophus ferrumequinum, and Pipistrellus abramus) inhabiting South Korea. Exogenous retroviruses (XRVs) were detected in the tissue samples of R. ferrumequinum individuals by PCR assay. Proviruses were identified in all tissue samples through viral quantification using a digital PCR assay per organ (lung, intestine, heart, brain, wing, kidney, and liver), with viral loads varying greatly between each organ. In phylogenetic analysis based on the whole genome, the Korean bat retroviruses and the R. ferrumequinum retrovirus (RfRV) strain formed a new clade distinct from the Gammaretrovirus clade. The phylogenetic results determined these viruses to be RfRV-like viruses. In the Simplot comparison, Korean RfRV-like viruses exhibited relatively strong fluctuated patterns in the latter part of the envelope gene area compared to other gene areas. Several point mutations within this region (6,878-7,774 bp) of these viruses were observed compared to the RfRV sequence. One Korean RfRV-like virus (named Y4b strain) was successfully recovered in the Raw 264.7 cell line, and virus particles replicated in the cells were confirmed by transmission electron microscopy. RfRVs (or RfRV-like viruses) have been spreading since their first discovery in 2012, and the Korean RfRV-like viruses were assumed to be XRVs that evolved from RfRV.IMPORTANCER. ferrumequinum retrovirus (RfRV)-like viruses were identified in greater horseshoe bats in South Korea. These RfRV-like viruses were considered exogenous retroviruses (XRVs) that emerged from RfRV. Varying amounts of provirus detected in different organs suggest ongoing viral activity, replication, and de novo integration in certain organs. Additionally, the successful recovery of the virus in the Raw 264.7 cell line provides strong evidence supporting their status as XRVs. These viruses have now been identified in South Korea and, more recently, in Kenya since RfRV was discovered in China in 2012, indicating that RfRVs (or RfRV-like viruses) have spread worldwide.

Role of oxygen reserve index monitoring in patients undergoing robot-assisted radical prostatectomy: a retrospective study.

PURPOSE: Robot-assisted radical prostatectomy (RARP) is a common surgical procedure for the treatment of prostate cancer. Although beneficial, it can lead to intraoperative hypoxia due to high-pressure pneumoperitoneum and Trendelenburg position. This study explored the use of oxygen reserve index (ORi) to monitor and predict hypoxia during RARP. METHODS: A retrospective analysis was conducted on 329 patients who underwent RARP at the Seoul National University Bundang Hospital between July 2021 and March 2023. Various pre- and intraoperative variables were collected, including ORi values. The relationship between ORi values and hypoxia occurrence was assessed using receiver operating characteristic curves and logistic regression analysis. RESULTS: Intraoperative hypoxia occurred in 18.8% of the patients. The receiver operating characteristic curve showed a satisfactory area under the curve of 0.762, with the ideal ORi cut-off value for predicting hypoxia set at 0.16. Sensitivity and specificity were 64.5% and 75.7%, respectively. An ORi value of < 0.16 and a higher body mass index were identified as independent risk factors of hypoxia during RARP. CONCLUSIONS: ORi monitoring provides a non-invasive approach to predict intraoperative hypoxia during RARP, enabling early management. Additionally, the significant relationship between a higher body mass index and hypoxia underscores the importance of individualized patient assessment.

Dynamic Contrast-enhanced MRI Quantification of Altered Vascular Permeability in Autoimmune Encephalitis.

Background Blood-brain barrier (BBB) permeability change is a possible pathologic mechanism of autoimmune encephalitis. Purpose To evaluate the change in BBB permeability in patients with autoimmune encephalitis as compared with healthy controls by using dynamic contrast-enhanced (DCE) MRI and to explore its predictive value for treatment response in patients. Materials and Methods This single-center retrospective study included consecutive patients with probable or possible autoimmune encephalitis and healthy controls who underwent DCE MRI between April 2020 and May 2021. Automatic volumetric segmentation was performed on three-dimensional T1-weighted images, and volume transfer constant (Ktrans) values were calculated at encephalitis-associated brain regions. Ktrans values were compared between the patients and controls, with adjustment for age and sex with use of a nonparametric approach. The Wilcoxon rank sum test was performed to compare Ktrans values of the good (improvement in modified Rankin Scale [mRS] score of at least two points or achievement of an mRS score of ≤2) and poor (improvement in mRS score of less than two points and achievement of an mRS score >2) treatment response groups among the patients. Results Thirty-eight patients with autoimmune encephalitis (median age, 38 years [IQR, 29-59 years]; 20 [53%] female) and 17 controls (median age, 71 years [IQR, 63-77 years]; 12 [71%] female) were included. All brain regions showed higher Ktrans values in patients as compared with controls (P < .001). The median difference in Ktrans between the patients and controls was largest in the right parahippocampal gyrus (25.1 × 10-4 min-1 [95% CI: 17.6, 43.4]). Among patients, the poor treatment response group had higher baseline Ktrans values in both cerebellar cortices (P = .03), the left cerebellar cortex (P = .02), right cerebellar cortex (P = .045), left cerebral cortex (P = .045), and left postcentral gyrus (P = .03) than the good treatment response group. Conclusion DCE MRI demonstrated that BBB permeability was increased in all brain regions in patients with autoimmune encephalitis as compared with controls, and baseline Ktrans values were higher in patients with poor treatment response in the cerebellar cortex, left cerebral cortex, and left postcentral gyrus as compared with the good response group. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Filippi and Rocca in this issue.

Intraoperative Brainstem Auditory Evoked Potentials and Postoperative Nausea and Vomiting After Microvascular Decompression.

BACKGROUND: We performed this study to investigate the effect of intraoperative brainstem auditory evoked potential (IBAEP) changes on the development of postoperative nausea and vomiting (PONV) after microvascular decompression (MVD) for neurovascular cross compression. METHODS: A total of 373 consecutive cases were treated with MVD. The use of rescue antiemetics after surgery was used as an objective indicator of PONV. IBAEP monitoring was routinely performed in all. RESULTS: The use of rescue antiemetics was significantly associated with female sex (OR = 3.427; 95% CI, 2.077-5.654; P < 0.001), PCA use (OR = 3.333; 95% CI, 1.861-5.104; P < 0.001), and operation time (OR = 1.017; 95% CI, 1.008-1.026; P < 0.001). A Wave V peak delay of more than 1.0 milliseconds showed a significant relation with the use of rescue antiemetics (OR = 1.787; 95% CI, 1.114-2.867; P = 0.016) and a strong significant relation with the use of rescue antiemetics more than 5 times (OR = 2.426; 95% CI, 1.372-4.290; P = 0.002). CONCLUSIONS: A wave V peak delay of more than 1.0 milliseconds might have value as a predictor of PONV after MVD. More detailed neurophysiological studies will identify the exact pathophysiology underlying PONV after MVD.

Reduced toxicity (FluBu3) versus myeloablative (BuCy) conditioning in acute myeloid leukemia patients who received first allogeneic hematopoietic stem cell transplantation in measurable residual disease-negative CR1.

In the present study, reduced toxicity (FluBu3) and myeloablative (BuCy) conditioning were compared in patients with AML who received first allogeneic HSCT in MRD-negative CR1. The study included 124 adult patients who underwent HSCT from an HLA-matched (8/8) sibling, unrelated, or 1-locus mismatched (7/8) unrelated donor (MMUD). The median age was 45 years and intermediate cytogenetics comprised majority (71.8%). The 2-year OS, RFS, CIR and NRM for BuCy (n = 78, 62.9%) and FluBu3 (n = 46, 37.1%) groups were 78.3% and 84.5% (p = 0.358), 78.0% and 76.3% (p = 0.806), 7.7% and 21.5% (p = 0.074) and 14.3% and 2.2% (p = 0.032), respectively. At the time of data cut-off, relapse and NRM were the main causes of HSCT failure in each of the FluBu3 and BuCy arms. Among patients, 75% of relapsed FluBu3 patients had high-risk features of either poor cytogenetics or FLT3-ITD mutation compared with 16.7% of BuCy patients. The majority of NRM in the BuCy group was due to GVHD (73%), half of whom received MMUD transplantation. To conclude, the FluBu3 reduced toxicity conditioning showed comparable post-transplant OS and RFS to BuCy and was associated with significantly reduced NRM that was offset by a trend towards higher risk of relapse even in MRD-negative CR1 population.

The impact of MEIS1 TALE homeodomain transcription factor knockdown on glioma stem cell growth.

Myeloid ecotropic virus insertion site 1 (MEIS1) is a HOX co-factor necessary for organ development and normal hematopoiesis. Recently, MEIS1 has been linked to the development and progression of various cancers. However, its role in gliomagenesis particularly on glioma stem cells (GSCs) remains unclear. Here, we demonstrate that MEIS1 is highly upregulated in GSCs compared to normal, and glioma cells and to its differentiated counterparts. Inhibition of MEIS1 expression by shRNA significantly reduced GSC growth in both in vitro and in vivo experiments. On the other hand, integrated transcriptomics analyses of glioma datasets revealed that MEIS1 expression is correlated to cell cycle-related genes. Clinical data analysis revealed that MEIS1 expression is elevated in high-grade gliomas, and patients with high MEIS1 levels have poorer overall survival outcomes. The findings suggest that MEIS1 is a prognostic biomarker for glioma patients and a possible target for developing novel therapeutic strategies against GBM.

Comparison of blood loss between intra-articular microporous polysaccharide hemospheres powder and tranexamic acid following primary total knee arthroplasty.

Total knee arthroplasty (TKA) is associated with substantial blood loss and tranexamic acid (TXA) effectively reduces postoperative bleeding. Although it is known that there is no difference between intravenous or intra-articular (IA) injection, the general interest is directed towards topical hemostatic agents regarding thromboembolic events in high-risk patients. This study aimed to compare the blood conservation effects of IA MPH powder and TXA in patients undergoing primary TKA. We retrospectively analyzed 103 patients who underwent primary TKA between June 2020 and December 2021. MPH powder was applied to the IA space before capsule closure (MPH group, n = 51). TXA (3 g) was injected via the drain after wound closure (TXA group, n = 52). All patients underwent drain clamping for three postoperative hours. The primary outcome was the drain output, and the secondary outcomes were the postoperative hemoglobin (Hb) levels during the hospitalization period and the perioperative blood transfusion rates. An independent Student's t-test was used to determine differences between the two groups. The drain output in the first 24 h after surgery was significantly higher in the MPH group than in the TXA group. The postoperative Hb levels were significantly lower in the MPH group than in the TXA group. In patients with simultaneous bilateral TKA, there was a significant difference in the blood transfusion volumes and the rates between groups. It is considered that IA MPH powder cannot replace IA TXA because of an inferior efficacy in reducing blood loss and maintaining postoperative Hb levels in the early postoperative period after primary TKA. Moreover, in the case of simultaneous bilateral TKA, we do not recommend the use of IA MPH powder because it was notably less effective in the field of transfusion volume and rate.

SIRT1 ISGylation accelerates tumor progression by unleashing SIRT1 from the inactive state to promote its deacetylase activity.

ISG15 is an interferon-stimulated ubiquitin-like protein (UBL) with multifaceted roles as a posttranslational modifier in ISG15 conjugation (ISGylation). However, the mechanistic consequences of ISGylation in cancer have not been fully elucidated, largely due to a lack of knowledge on the ISG15 target repertoire. Here, we identified SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, as a new target for ISGylation. SIRT1 ISGylation impairs the association of SIRT1 with its negative regulator, deleted in breast cancer 1 (DBC1), which unleashes SIRT1 from its inactive state and leads to an increase in its deacetylase activity. Importantly, SIRT1 ISGylation promoted lung cancer progression and limited lung cancer cell sensitivity to DNA damage-based therapeutics in vivo and in vitro models. The levels of ISG15 mRNA and protein were significantly higher in lung cancer tissues than in adjacent normal tissues. Accordingly, elevated expression of SIRT1 and ISG15 was associated with poor prognosis in lung cancer patients, a finding that could be translated for lung cancer patient stratification and disease outcome evaluation. Taken together, our findings provide a mechanistic understanding of the regulatory effect of SIRT1 ISGylation on tumor progression and therapeutic efficacy in lung cancer.