Preparation and Evaluation of Inhalable Microparticles with Improved Aerodynamic Performance and Dispersibility Using L-Leucine and Hot-Melt Extrusion.

Dry-powder inhalers (DPIs) are valued for their stability but formulating them is challenging due to powder aggregation and limited flowability, which affects drug delivery and uniformity. In this study, the incorporation of L-leucine (LEU) into hot-melt extrusion (HME) was proposed to enhance dispersibility while simultaneously maintaining the high aerodynamic performance of inhalable microparticles. This study explored using LEU in HME to improve dispersibility and maintain the high aerodynamic performance of inhalable microparticles. Formulations with crystalline itraconazole (ITZ) and LEU were made via co-jet milling and HME followed by jet milling. The LEU ratio varied, comparing solubility, homogenization, and aerodynamic performance enhancements. In HME, ITZ solubility increased, and crystallinity decreased. Higher LEU ratios in HME formulations reduced the contact angle, enhancing mass median aerodynamic diameter (MMAD) size and aerodynamic performance synergistically. Achieving a maximum extra fine particle fraction of 33.68 ± 1.31% enabled stable deep lung delivery. This study shows that HME combined with LEU effectively produces inhalable particles, which is promising for improved drug dispersion and delivery.

CLEMENT: genomic decomposition and reconstruction of non-tumor subclones.

Genome-level clonal decomposition of a single specimen has been widely studied; however, it is mostly limited to cancer research. In this study, we developed a new algorithm CLEMENT, which conducts accurate decomposition and reconstruction of multiple subclones in genome sequencing of non-tumor (normal) samples. CLEMENT employs the Expectation-Maximization (EM) algorithm with optimization strategies specific to non-tumor subclones, including false variant call identification, non-disparate clone fuzzy clustering, and clonal allele fraction confinement. In the simulation and in vitro cell line mixture data, CLEMENT outperformed current cancer decomposition algorithms in estimating the number of clones (root-mean-square-error = 0.58-0.78 versus 1.43-3.34) and in the variant-clone membership agreement (∼85.5% versus 70.1-76.7%). Additional testing on human multi-clonal normal tissue sequencing confirmed the accurate identification of subclones that originated from different cell types. Clone-level analysis, including mutational burden and signatures, provided a new understanding of normal-tissue composition. We expect that CLEMENT will serve as a crucial tool in the currently emerging field of non-tumor genome analysis.

Sugary snack restriction enhances body composition improvement in overweight women engaging in non-face-to-face walking during COVID-19.

Introduction: This study assesses the impact of dietary modification, specifically sugary snack restriction, in conjunction with a brisk walking program on overweight management in young overweight women, with a focus on changes in body composition and glucose metabolism. Method: An 8-week randomized controlled trial was conducted amidst the COVID-19 pandemic, utilizing a remote intervention approach to comply with health guidelines and ensure participant safety. The study's remote nature highlights adaptability in health interventions during challenging periods, such as the COVID-19 pandemic. Twenty-one overweight Korean women aged 20-39, with an average BMI of 24.6, were selected for the study. They were divided into two groups: one engaging in brisk walking and the other combining this exercise with a sugary snack restriction, demonstrating the study's focus on comparative intervention efficacy. Results: The exercise-only group showed notable reductions in glucose, insulin, HOMA-IR (p < 0.05), and total cholesterol levels (p < 0.01). In contrast, the group that combined exercise with dietary modification displayed more pronounced improvements in body weight, fat mass, and waist circumference (p < 0.05). This differential outcome emphasizes the added benefit of integrating dietary control with physical activity. Discussion: The findings suggest that adding a dietary component, particularly a sugary snack restriction, to an exercise regimen can significantly enhance the effectiveness of overweight management in young women. This study underscores the importance of holistic lifestyle interventions that combine dietary and physical activity modifications for improved health outcomes.

A novel approach to alleviate acetaminophen-induced hepatotoxicity with hybrid balloon flower root-derived exosome-like nanoparticles (BDEs) with silymarin via inhibition of hepatocyte MAPK pathway and apoptosis.

INTRODUCTION: Balloon flower root-derived exosome-like nanoparticles (BDEs) have recently been proposed as physiologically active molecules with no cytotoxicity. However, the therapeutic effects of drug-induced hepatotoxicity of BDEs have not been elucidated. BDEs contain a large amount of platycodin D, which is widely known to be effective in regulating inflammation and ameliorating systemic toxicity. Thus, the main therapeutic activity of BDEs is attributed to inhibiting the inflammatory response and alleviating toxicity. In this study, we fabricated the hybrid BDEs fused with liposomes containing silymarin (SM) to enhance the synergistic effect on inhibition of acetaminophen-induced hepatotoxicity (APAP). OBJECTIVE: Considering the potential therapeutic effects of BDEs, and the potential to achieve synergistic effects to improve therapeutic outcomes, we constructed hybrid BDEs with a soy lecithin-based liposome loaded with SM. Since liposomes can provide higher thermal stability and have greater structural integrity, these might be more resistant to clearance and enzymatic degradation of drug molecules. METHODS: Hybrid BDEs with liposome-loaded SM (BDEs@lipo-SM) were fabricated by thin-film hydration and extrusion. BDEs@lipo-SM were characterized using dynamic light scattering and high-performance liquid chromatography. After confirmation of the physical properties of BDEs@lipo-SM, various therapeutic properties were evaluated. RESULTS: BDEs@lipo-SM were internalized by hepatocytes and immune cells and significantly decreased mRNA expression of apoptosis and inflammation-relevant cytokines by inhibiting the hepatocyte MAPK pathway. BDEs@lipo-SM significantly induced an increase in glutathione levels and inhibited APAP-induced hepatotoxicity. CONCLUSION: From this study, we know that BDEs are reliable and safe nanovesicles containing natural metabolites derived from balloon flower, and they can facilitate intercellular communication. BDEs are also easily modified to enhance drug loading capacity, targeting effects, and long-term accumulation in vivo. BDEs@lipo-SM have therapeutic benefits for acute liver injury and can alleviate cell death and toxicity. They can be efficiently delivered to the liver and effectively inhibit APAP-induced hepatotoxicity by inhibiting the MAPK signaling pathway and apoptosis, which accelerates liver recovery in the APAP-induced acute liver injury model. These findings highlight that BDEs represent an attractive delivery vehicle for drug delivery.

Effects of bisphenol A on reproduction, oxidative stress, and lipid regulation in the marine rotifer Brachionus plicatilis.

This study reports the effects of bisphenol A (BPA) on the rotifer Brachionus plicatilis, focusing on growth performance, reproductive output, oxidative stress responses, and lipid metabolism genes. High BPA levels disrupted peak daily offspring production and led to oxidative stress and increased superoxide dismutase and catalase activity. The research identified distinctive monoacylglycerol O-acyltransferase (MGAT) and diacylglycerol O-acyltransferase (DGAT) genes in B. plicatilis, B. rotundiformis, and B. koreanus, enhancing understanding of lipid metabolism in these species. BPA exposure significantly altered MGAT and DGAT expression, and feeding status affected these regulatory patterns. When food was unavailable, BPA reduced DGAT2 and MGAT2a expression. However, under feeding conditions, DGAT2 and MGAT1 levels increased, indicating that nutritional status and BPA exposure interact to affect gene expression.

Disruption of early embryonic development in mice by polymethylmethacrylate nanoplastics in an oxidative stress mechanism.

Polymethylmethacrylate (PMMA) has been used in many products, such as acrylic glass, and is estimated to reach 5.7 million tons of production per year by 2028. Thus, nano-sized PMMA particles in the environment are highly likely due to the weathering process. However, information on the hazards of nanoplastics, including PMMA in mammals, especially reproductive toxicity and action mechanism, is scarce. Herein, we investigated the effect of PMMA nanoplastics on the female reproductive system of mice embryos during pre-implantation. The treated plastic particles in embryos (10, 100, and 1000 µg/mL) were endocytosed into the cytoplasm within 30 min, and the blastocyst development and indices of embryo quality were significantly decreased from at 100 µg/mL. Likewise, the transfer of nanoplastic-treated embryos at 100 µg/mL decreased the morula implantation rate on the oviduct of pseudopregnant mice by 70%, calculated by the pregnant individual, and 31.8% by the number of implanted embryos. The PMMA nanoplastics at 100 µg/mL significantly increased the cellular levels of reactive oxygen species in embryos, which was not related to the intrinsic oxidative potential of nanoplastics. This study highlights that the nanoplastics that enter systemic circulation can affect the early stage of embryos. Thus, suitable action mechanisms can be designed to address nanoplastic occurrence.

Comprehensive analysis of donor-site chest deformities after autologous costal cartilage microtia reconstruction: A systematic review.

BACKGROUND: Autologous costal cartilage has gained widespread acceptance as an important material for ear reconstruction in patients with microtia. Despite its recognition as being "worth the trade-off," attention should be directed toward donor-site deformities. This systematic review focused on existing English literature related to microtia reconstruction and aimed to reveal the incidence of chest wall deformities and assess the effectiveness of the various proposed surgical techniques aimed at reducing donor-site morbidities. METHODS: A comprehensive search was conducted on Pubmed and OVID using the keywords "microtia," and "chest deformity" or "rib harvest." Articles were screened based on predefined inclusion and exclusion criteria. Data acquisition encompassed patient demographics, employed surgical techniques, methods for evaluating chest deformity, and incidence of associated complications. RESULTS: Among the 362 identified articles, 21 met the inclusion criteria. A total of 2600 cases involving 2433 patients with microtia were analyzed in this review. Perichondrium preservation during cartilage harvesting led to a significant reduction in chest deformities. However, the wide incidence range (0% to 50%) and the lack of specific assessment methods suggested potential underestimation. Computed tomography revealed reduced chest wall growth in the transverse and sagittal directions, resulting in decreased thoracic area. Innovative surgical techniques have shown promising results in reducing chest deformities. CONCLUSIONS: Although a quantitative analysis was not feasible, objective evidence of deformities was established through computed tomography scans. This analysis highlighted the need for dedicated studies with larger sample sizes to further advance our understanding of chest wall deformities in microtia reconstruction.

Association between the transition to metabolically unhealthy obesity and lifestyle behavior: A nationwide cohort study.

OBJECTIVES: To identify the characteristics of individuals transitioning from metabolically healthy obesity (MHO) to unhealthy obesity and the factors influencing the change. DESIGN: This is a nationwide cohort study using data from the National Health Insurance Service in South Korea. SAMPLE: Individuals with obesity but metabolically healthy in 2009 and 2010 and those still obese 4 years later were selected. MEASUREMENTS: Sociodemographic, physical, metabolic, and health behavior variables were collected, and logistic regression was used to find an association with the transition. RESULTS: We analyzed 1,564,467 individuals, observing significant differences in all variables and the transition from MHO to unhealthy obesity. Among males, the transition was associated with smoking and drinking positively and physical activity negatively. Among females, drinking demonstrated a negative correlation. Regardless of age, regular exercise was negatively associated with the transition for all individuals. Except for older adults, all age groups showed a positive correlation with smoking and drinking. CONCLUSIONS: Considering the significant factors in the transition, it is essential to develop and implement interventions varied by gender and age to delay and prevent the change in metabolic status. The necessity of developing interventions enables individuals to engage in regular exercise, regardless of age and gender.

Effects of post-exercise intake of exogenous lactate on energy substrate utilization at rest.

PURPOSE: This study investigated the effects of exogenous lactate intake on energy metabolism during 1 h of rest after acute exercise. METHODS: Eight-week-old ICR mice were randomly divided into four groups: SED (no treatment), EXE (exercise only), LAC (post-exercise oral lactate administration), and SAL (post-exercise saline administration) (n=8 per group). The exercise intensity was at VO2max 80% at 25 m/min and 15° slope for 50 min. After acute exercise, the LAC and SAL groups ingested lactate and saline orally, respectively, and were allowed to rest in a chamber. Energy metabolism was measured for 1 h during the resting period. RESULTS: LAC and SAL group mice ingested lactate and saline, respectively, after exercise and the blood lactate concentration was measured 1 h later through tail blood sampling. Blood lactate concentration was not significantly different between the two groups. Energy metabolism measurements under stable conditions revealed that the respiratory exchange ratio in the LAC group was significantly lower than that in the SAL group. Additionally, carbohydrate oxidation in the LAC group was significantly lower than that in the SAL group at 10-25 min. No significant difference was observed in the fat oxidation level between the two groups. CONCLUSION: We found that post-exercise lactate intake modified the respiratory exchange ratio after 1 h of rest. In addition, acute lactate ingestion inhibits carbohydrate oxidation during the post-exercise recovery period.

Optimizing Embryo Collection for Application of CRISPR/Cas9 System and Generation of Fukutin Knockout Rat Using This Method.

Rat animal models are widely used owing to their relatively superior cognitive abilities and higher similarity compared with mouse models to human physiological characteristics. However, their use is limited because of difficulties in establishing embryonic stem cells and performing genetic modifications, and insufficient embryological research. In this study, we established optimal superovulation and fertilized-egg transfer conditions, including optimal hormone injection concentration (≥150 IU/kg of PMSG and hCG) and culture medium (mR1ECM), to obtain high-quality zygotes and establish in vitro fertilization conditions for rats. Next, sgRNA with optimal targeting activity was selected by performing PCR analysis and the T7E1 assay, and the CRISPR/Cas9 system was used to construct a rat model for muscular dystrophy by inducing a deficiency in the fukutin gene without any off-target effect detected. The production of fukutin knockout rats was phenotypically confirmed by observing a drop-in body weight to one-third of that of the control group. In summary, we succeeded in constructing the first muscular dystrophy disease rat model using the CRISPR/CAS9 system for increasing future prospects of producing various animal disease models and encouraging disease research using rats.

Quercetin Induces Mitochondrial Apoptosis and Downregulates Ganglioside GD3 Expression in Melanoma Cells.

Malignant melanoma represents a form of skin cancer characterized by a bleak prognosis and heightened resistance to traditional therapies. Quercetin has demonstrated notable anti-carcinogenic, anti-inflammatory, anti-oxidant, and pharmacological effects across various cancer types. However, the intricate relationship between quercetin's anti-cancer properties and ganglioside expression in melanoma remains incompletely understood. In this study, quercetin manifests specific anti-proliferative, anti-migratory, and cell-cycle arrest effects, inducing mitochondrial dysfunction and apoptosis in two melanoma cancer cell lines. This positions quercetin as a promising candidate for treating malignant melanoma. Moreover, our investigation indicates that quercetin significantly reduces the expression levels of ganglioside GD3 and its synthetic enzyme. Notably, this reduction is achieved through the inhibition of the FAK/paxillin/Akt signaling pathway, which plays a crucial role in cancer development. Taken together, our findings suggest that quercetin may be a potent anti-cancer drug candidate for the treatment of malignant melanoma.

AM-18002, a derivative of natural anmindenol A, enhances radiosensitivity in mouse breast cancer cells.

Natural anmindenol A isolated from the marine-derived bacteria Streptomyces sp. caused potent inhibition of inducible nitric oxide synthase without any significant cytotoxicity. This compound consists of a structurally unique 3,10-dialkylbenzofulvene skeleton. We previously synthesized and screened the novel derivatives of anmindenol A and identified AM-18002, an anmindenol A derivative, as a promising anticancer agent. The combination of AM-18002 and ionizing radiation (IR) improved anticancer effects, which were exerted by promoting apoptosis and inhibiting the proliferation of FM3A mouse breast cancer cells. AM-18002 increased the production of reactive oxygen species (ROS) and was more effective in inducing DNA damage. AM-18002 treatment was found to inhibit the expansion of myeloid-derived suppressor cells (MDSC), cancer cell migration and invasion, and STAT3 phosphorylation. The AM-18002 and IR combination synergistically induced cancer cell death, and AM-18002 acted as a potent anticancer agent by increasing ROS generation and blocking MDSC-mediated STAT3 activation in breast cancer cells.

Pediatric Benign Paroxysmal Positional Vertigo: Degree of Nystagmus and Concurrent Dizziness Differs from Adult BPPV.

Background: Benign paroxysmal positional vertigo (BPPV) is characterized by brief, intense episodes of vertigo triggered by abrupt changes in head position. It is generally accepted as being most common in adults, while it is regarded as rare in children. It is necessary to compare the disease between pediatric and adult patients for a better understanding of the disease's characteristics and its natural history. This study aimed to identify the clinical characteristics of BPPV in children and compare them with those of adult BPPV patients. Methods: All children ≤ 18 years old who were diagnosed with BPPV were selected by searching the electronic database of our hospital. Clinical features were identified by medical record review. For adult patients, we collected data from patients > 19 years of age. Results: A total of 30 pediatric (13.65 ± 4.15 years old) and 264 adult patients (60.86 ± 13.74 years old) were included in the study. Among pediatric patients, the lateral canals were involved in 80% and the posterior canals in 16.67%. In adult patients, the lateral and posterior canals were involved similarly (p = 0.007). The degree of nystagmus in pediatric patients was 6.82 ± 12.09, while in adults it was 15.58 ± 20.90 (p < 0.001). The concurrent dizziness disorder was higher in the pediatric group and recurrence was higher in the adult group. In the regression analysis, it was found that adult patients had a stronger nystagmus with a value of 6.206 deg/sec, and the risk of concurrent dizziness disorder was found to be 5.413 times higher in the pediatric group (p < 0.05). Conclusions: BPPV occurs in pediatric patients with lower prevalence, but it cannot be overlooked. In the pediatric group, a relatively high proportion of patients demonstrated lateral canal involvement, weaker nystagmus, and additional dizziness disorder.

Chronic Administration of Exogenous Lactate Increases Energy Expenditure during Exercise through Activation of Skeletal Muscle Energy Utilization Capacity in Mice.

We compared the effects of chronic exogenous lactate and exercise training, which influence energy substrate utilization and body composition improvements at rest and during exercise, and investigated the availability of lactate as a metabolic regulator. The mice were divided into four groups: CON (sedentary + saline), LAC (sedentary + lactate), EXE (exercise + saline), and EXLA (exercise + lactate). The total experimental period was set at 4 weeks, the training intensity was set at 60-70% VO2max, and each exercise group was administered a solution immediately after exercise. Changes in the energy substrate utilization at rest and during exercise, the protein levels related to energy substrate utilization in skeletal muscles, and the body composition were measured. Lactate intake and exercise increased carbohydrate oxidation as a substrate during exercise, leading to an increased energy expenditure and increased protein levels of citrate synthase and malate dehydrogenase 2, key factors in the TCA(tricarboxylic acid) cycle of skeletal muscle. Exercise, but not lactate intake, induced the upregulation of the skeletal muscle glucose transport factor 4 and a reduction in body fat. Hence, chronic lactate administration, as a metabolic regulator, influenced energy substrate utilization by the skeletal muscle and increased energy expenditure during exercise through the activation of carbohydrate metabolism-related factors. Therefore, exogenous lactate holds potential as a metabolic regulator.

Enhancing the anticancer effect of androgen deprivation therapy by monocarboxylate transporter 1 inhibitor in prostate cancer cells.

BACKGROUND: Tumor initiation and progression necessitate a metabolic shift in cancer cells. Consequently, the progression of prostate cancer (PCa), a leading cause of cancer-related deaths in males globally, involves a shift from lipogenic to glycolytic metabolism. Androgen deprivation therapy (ADT) serves as the standard treatment for advanced-stage PCa. However, despite initial patient responses, castrate resistance emerges ultimately, necessitating novel therapeutic approaches. Therefore, in this study, we aimed to investigate the role of monocarboxylate transporters (MCTs) in PCa post-ADT and evaluate their potential as therapeutic targets. METHODS: PCa cells (LNCaP and C4-2 cell line), which has high prostate-specific membrane antigen (PSMA) and androgen receptor (AR) expression among PCa cell lines, was used in this study. We assessed the expression of MCT1 in PCa cells subjected to ADT using charcoal-stripped bovine serum (CSS)-containing medium or enzalutamide (ENZ). Furthermore, we evaluated the synergistic anticancer effects of combined treatment with ENZ and SR13800, an MCT1 inhibitor. RESULTS: Short-term ADT led to a significant upregulation in folate hydrolase 1 (FOLH1) and solute carrier family 16 member 1 (SLC16A1) gene levels, with elevated PSMA and MCT1 protein levels. Long-term ADT induced notable changes in cell morphology with further upregulation of FOLH1/PSMA and SLC16A1/MCT1 levels. Treatment with ENZ, a nonsteroidal anti-androgen, also increased PSMA and MCT1 expression. However, combined therapy with ENZ and SR13800 led to reduced PSMA level, decreased cell viability, and suppressed expression of cancer stem cell markers and migration indicators. Additionally, analysis of human PCa tissues revealed a positive correlation between PSMA and MCT1 expression in tumor regions. CONCLUSIONS: Our results demonstrate that ADT led to a significant upregulation in MCT1 levels. However, the combination of ENZ and SR13800 demonstrated a promising synergistic anticancer effect, highlighting a potential therapeutic significance for patients with PCa undergoing ADT.

RCHY1 and OPTN are required for melanophagy, selective autophagy of melanosomes.

Melanosomes are specific organelles dedicated to melanin synthesis and accumulation in melanocytes. Autophagy is suggestively involved in melanosome degradation, although the potential underlying molecular mechanisms remain elusive. In selective autophagy, autophagy receptors and E3-ligases are the key factors conferring cargo selectivity. In B16F10 cells, ß-mangostin efficiently induced melanosome degradation without affecting other organelles such as mitochondria, peroxisomes, and the endoplasmic reticulum. Among various autophagy receptors, optineurin (OPTN) contributes TANK-binding kinase 1 (TBK1)-dependently to melanosome degradation and its knockdown inhibited ß-mangostin-mediated melanosome degradation. OPTN translocation to melanosomes was dependent on its ubiquitin-binding domain. Moreover, OPTN-mediated TBK1 activation and subsequent TBK1-mediated S187 OPTN phosphorylation were essential for melanosome degradation. ß-mangostin increased K63-linked melanosome ubiquitination. Finally, the E3-ligase RCHY1 knockdown inhibited the melanosome ubiquitination required for OPTN- and TBK1-phosphorylation as well as melanosome degradation. This study suggests that melanophagy, melanosome-selective autophagy, contributes to melanosome degradation, and OPTN and RCHY1 are an essential autophagy receptor and a E3-ligase, respectively, conferring cargo selectivity in melanophagy.

Reducing the carbon footprint of operating rooms through education on the effects of inhalation anesthetics on global warming: A retrospective study.

Environmental concerns, especially global warming, have prompted efforts to reduce greenhouse gas emissions. Healthcare systems, including anesthesia practices, contribute to these emissions. Inhalation anesthetics have a significant environmental impact, with desflurane being the most concerning because of its high global warming potential. This study aimed to educate anesthesiologists on the environmental impact of inhalation anesthetics and assess changes in awareness and practice patterns, specifically reducing desflurane use. This study included data from patients who underwent surgery under general anesthesia 1 month before and after education on the effects of inhalation anesthetics on global warming. The primary endpoint was a change in inhalational anesthetic use. Secondary endpoints included changes in carbon dioxide equivalent (CO2e) emissions, driving equivalent, and medical costs. After the education, desflurane use decreased by 50%, whereas sevoflurane use increased by 50%. This shift resulted in a reduction in the overall amount of inhalational anesthetics used. The total CO2e and driving-equivalent values decreased significantly. The cost per anesthesia case decreased, albeit to a lesser extent than expected. Education on the environmental impact of inhalation anesthetics has successfully altered anesthesiologists' practice patterns, leading to reduced desflurane usage. This change has resulted in decreased CO2e emissions and has had a positive effect on mitigating global warming. However, further research is required to assess the long-term impact of such education and the variability in practice patterns across different institutions.

Microsurgical reconstruction using thoracoacromial vessels as recipients for complicated chest wall defects.

BACKGROUND: Free tissue transfer is often required for the reconstruction of complex and deep anterior chest wall wounds, for which the identification of suitable recipient vessels is crucial. Although the internal mammary arteries (IMAs) are a representative option, identifying secondary options when these vessels are compromised remains a challenge. This report evaluated the efficacy of using the thoracoacromial vessels (TAVs) as recipients for chest wall reconstruction by reviewing our experience. METHODS: We conducted a retrospective review of patients undergoing free-flap-based chest wall reconstruction using TAVs as recipient vessels from February 2020 to March 2023. Patient demographics and surgery-related characteristics data were collected. The primary outcome of interest was the occurrence of flap perfusion-related complications. RESULTS: In total, 12 cases utilized TAVs as recipients, primarily for defects following sternotomy, where bilateral IMA was unavailable due to prior surgery. The TAVs with reliable perfusion were consistently identified beneath the pectoralis major muscle. The anterolateral thigh flap was predominantly employed, with musculocutaneous or chimeric flaps introduced for bony defects. The mean pedicle length of the harvested flap was 7.2 cm (range, 3-13), and in cases with a vascular gap, the pedicle was extended using an arteriovenous interposition graft. This resulted in a mean pedicle length needed to reach recipient vessels of 9.9 cm (range, 6.5-19). All flaps survived, with only one experiencing partial necrosis. CONCLUSIONS: The TAV could be considered as an attractive alternative recipient vessel in microsurgical reconstruction of complicated chest wall defects when the use of IMA is not feasible.

Comprehensive RNA-sequencing analysis of colorectal cancer in a Korean cohort.

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.

Lactate administration induces skeletal muscle synthesis by influencing Akt/mTOR and MuRF1 in non-trained mice but not in trained mice.

The perception regarding lactate has changed over the past decades, and some of its physiological roles have gradually been revealed. However, the effects of exogenous lactate on skeletal muscle synthesis remain unclear. This study aimed to confirm the effects of a 5-week lactate administration and post-exercise lactate administration on skeletal muscle synthesis. Thirty-two Institute of Cancer Research mice were randomly assigned to non-trained + placebo, non-trained + lactate, trained + placebo, and trained + lactate groups. Furthermore, 3 g/kg of lactate or an equivalent volume of saline was immediately administered after exercise training (maximum oxygen uptake: 70%). Lactate administration and/or exercise training was performed 5 days/week for 5 weeks. After the experimental period, it was observed that lactate administration tended to elevate skeletal muscle weight, increased protein kinase B (p < 0.05) and mammalian target of rapamycin (p < 0.05) mRNA levels, and decreased muscle ring-finger protein-1 expression (p < 0.05). Lactate administration after exercise training significantly enhanced plantaris muscle weight; however, it had no additional effects on most signaling factors. This study demonstrated that a 5-week lactate administration could stimulate skeletal muscle synthesis, and lactate administration after exercise training may provide additional effects, such as increasing skeletal muscle.