Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. Methods: Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. Results: After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. Conclusions We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

Dural arteriovenous fistula (DAVF) is a rare condition affecting approximately 1.5% of 1,000,000 individuals annually. It frequently occurs in the transsigmoid and cavernous sinuses. An isolated sigmoid sinus is extremely rare and is treated by performing transfemoral transvenous embolization along the opposite transverse sinus.A 69-year-old woman presented with asymptomatic Borden type III/Cognard type III DAVF involving an isolated sigmoid sinus. She underwent a staged operation in which a navigation system was used to expose the sigmoid sinus in the operating room before transferring the patient to the angio suite for transvenous embolization.Various modalities have been used to treat DAVF, including surgical disconnection, transarterial embolization, transvenous embolization, and stereotactic radiosurgery. However, treating DAVF cases where the affected sinus is isolated can be challenging because an easily accessible surgical route may not be available. In this case, direct sinus cannulation and transvenous embolization were the most effective treatments.

Objective: : Microscopic microvascular decompression (MVD) has been considered to be a useful treatment modality for medically refractory hemifacial spasm (HFS) and trigeminal neuralgia. But, the advent of the endoscopic era has presented new possibilities to MVD surgery. While the microscope remains a valuable tool, the endoscope offers several advantages with comparable clinical outcomes. Thus, fully endoscopic MVD (E-MVD) could be a reasonable alternative to microscopic MVD. This paper explores the safety and efficacy of the fully E-MVD technique. Methods: : A single-center retrospective study was conducted in 25 patients diagnosed with HFS between September 2019 and July 2023. All surgeries were performed by a single neurosurgeon using the fully E-MVD technique without any assistance of a microscope. The study reviewed intraoperative brainstem auditory evoked potentials and disappearance of the lateral spread response. Outcomes were assessed based on the patients’ clinical status immediately after surgery and at their last follow-up. Complications, including facial palsy, hearing loss, ataxia, dysphagia, palsy of other cranial nerves, and cerebrospinal fluid leakage, were also examined. Results: : The most common offending artery was the anterior inferior cerebellar artery (AICA) in 15 cases (60.0%), followed by the posterior inferior cerebellar artery in eight cases (32.0%), vertebral artery (VA) in one case (4.0%), tandem lesions involving the AICA and VA in one case (4.0%). Ten patients (40.0%) had pre-operative facial palsy on the ipsilateral side, and eight patients (32.0%) experienced delayed facial palsy on the ipsilateral side, from which they fully recovered by the last follow-up. The median operation time was 105 minutes. All patients were symptom free immediately after surgery and at the last follow-up. One patient experienced a permanent complication, such as high-frequency hearing loss, from which he partially recovered over time. Conclusion : Fully E-MVD demonstrated similar clinical outcomes to microscopic MVD. It offered a similar complication rate, shorter operation time, and a panoramic view with a smaller craniectomy size. Although there is a learning curve associated with fully E-MVD, it presents a viable alternative in the endoscopic era.

Purpose: Studies have yielded contradictory results on whether donor sex and donor-recipient sex disparity affect hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT). The present study assessed whether donor sex or donor-recipient sex disparity affects HCC recurrence after LDLT at a high-volume center. Methods: This study included 772 HCC patients who underwent LDLT between January 2006 and December 2015 at Asan Medical Center. Patients were divided into 4 groups based on the sex of the donor and recipient: male-to-male (n = 490, 63.5%), male-to-female (n = 75, 9.7%), female-to-male (n = 170, 22.0%), and female-to-female (n = 37, 4.8%). Results: Disease-free survival (DFS; P = 0.372) and overall survival (OS; P = 0.591) did not differ significantly among the 4 groups. DFS also did not differ significantly between LDLT recipients with male and female donors (P = 0.792) or between male and female recipients (P = 0.084). After patient matching with an α-FP/des-γ-carboxy prothrombin/tumor volume score cutoff of 5logs, donor-recipient sex disparity did not significantly affect DFS (P = 0.598) or OS (P = 0.777). There were also no differences in DFS in matched LDLT recipients with male and female donors (P = 0.312) or between male and female recipients (P = 0.374). Conclusion Neither donor sex nor donor-recipient sex disparity significantly affected posttransplant HCC recurrence.

FLASH radiotherapy (FLASH RT) is a technique to deliver ultra-high dose rate in a fraction of a second. Evidence from experimental animal models suggest that FLASH RT spares various normal tissues including the lung, gastrointestinal track, and brain from radiation-induced toxicity (a phenomenon known as FLASH effect), which is otherwise commonly observed with conventional dose rate RT. However, it is not simply the ultra-high dose rate alone that brings the FLASH effect. Multiple parameters such as instantaneous dose rate, pulse size, pulse repetition frequency, and the total duration of exposure all need to be carefully optimized simultaneously. Furthermore it is critical to validate FLASH effects in an in vivo experimental model system. The exact molecular mechanism responsible for this FLASH effect is not yet understood although a number of hypotheses have been proposed including oxygen depletion and less reactive oxygen species (ROS) production by FLASH RT, and enhanced ability of normal tissues to handle ROS and labile iron pool compared to tumors. In this review, we briefly overview the process of ionization event and history of radiotherapy and fractionation of ionizing radiation. We also highlight some of the latest FLASH RT reviews and results with a special interest to neurocognitive protection in rodent model with whole brain irradiation. Lastly we discuss some of the issues remain to be answered with FLASH RT including undefined molecular mechanism, lack of standardized parameters, low penetration depth for electron beam, and tumor hypoxia still being a major hurdle for local control. Nevertheless, researchers are close to having all answers to the issues that we have raised, hence we believe that advancement of FLASH RT will be made more quickly than one can anticipate.