The alteration of LBX1 expression is associated with changes in parameters related to energy metabolism in mice.

The LBX1 gene is located near a single nucleotide polymorphism that is highly associated with susceptibility to adolescent idiopathic scoliosis and is considered one of the strongest candidate genes involved in the pathogenesis of this condition. We have previously found that loss of LBX1 from skeletal muscle results not only in spinal deformity but also in lean body mass, suggesting a potential role for LBX1 in energy metabolism. The purpose of the present study was to test this hypothesis by analyzing the phenotype of mice lacking LBX1 in skeletal muscle with a focus on energy metabolism. We found that loss of LBX1 rendered mice more resistant to high-fat diet-induced obesity, despite comparable food intake between mutant and control mice. Notably, the mutant mice exhibited improved glucose tolerance, increased maximal aerobic capacity, and higher core body temperature compared to control mice. In addition, we found that overexpression of LBX1 decreased glucose uptake in cultured cells. Taken together, our data show that LBX1 functions as a negative regulator of energy metabolism and that loss of LBX1 from skeletal muscle increases systemic energy expenditure resulting in lean body mass. The present study thus suggests a potential association between LBX1 dysfunction and lean body mass in patients with adolescent idiopathic scoliosis.

Relationship Between Sleep Quality and Quality of Life: Analysis of Hepatocellular Carcinoma Survivors.

BACKGROUND:  We analyzed the correlation between the Pittsburgh Sleep Quality Index (PSQI) subcategories (sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance, sleep medications, and daytime dysfunction) and a comprehensive measure of quality of life (QOL), the 36-Item Short Form Survey (SF-36) items, in patients with hepatocellular carcinoma (HCC) to determine the components that require intervention to improve QOL. METHODS: A total of 75 patients with recurrent HCC admitted to our hospital between May 2021 and May 2023 were included in this study. The QOL score was used for the SF-36 items, and the sleep disorder score was used for PSQI questionnaires. RESULTS: Correlations were found between sleep quality, sleep disturbance, and SF-36 for all QOL items and between sleep onset time and SF-36 for six QOL items: bodily pain, mental health, physical functioning, role-emotional, role-physical, and vitality. Correlations between daytime dysfunction and SF-36 were found for all QOL items, except for physical functioning. No correlation was found between sleep duration, sleep efficiency, sleep medications, and SF-36 for any QOL item. CONCLUSION: Sleep duration, sleep efficiency, and sleep medications may not contribute to QOL improvement in patients with HCC and sleep disturbances. Factors that improve sleep quality and sleep difficulty may contribute to QOL improvement. Therapeutic interventions aimed at improving general health and social functioning for sleep latency and physical functioning for daytime arousal difficulty are required.

Abrogation of LBX1 in skeletal muscle results in hypoplastic limbs and progressive kyphosis in mice.

LBX1 is a gene located near a single-nucleotide polymorphism, rs11190870, which is highly associated with susceptibility to adolescent idiopathic scoliosis. However, the potential involvement of LBX1 in the etiology of this spinal deformity has not been elucidated. In this study, we aimed to determine whether the lack of LBX1 in skeletal muscle results in spinal deformities in mice. We generated mutant mice in which the Lbx1 allele was conditionally excised under the control of a human muscle actin promoter. Mice lacking LBX1 from the skeletal muscle were fertile and available. The mutant mice had hypoplastic forelimbs and weighed less than control animals, but otherwise, there were no overt anomalies. The mice did not exhibit a scoliosis-like spinal deformity; however, they developed moderate kyphosis as they grew old. These observations indicated that LBX1 is involved in limb development and potentially in the maintenance of spinal curvature/alignment in mice.

Trabectedin suppresses osteosarcoma pulmonary metastasis in a mouse tumor xenograft model.

Osteosarcoma (OS) is the most common primary bone tumor that mainly affects adolescents and young adults. Although standard treatment modality can achieve up to 60%-70% 5-year survival rate, there has not been any substantial improvement over the past four decades. Furthermore, those presenting with pulmonary metastatic lesions often undergo a highly unfavorable clinical course. Therefore, there is a severely unmet clinical need to provide a more effective treatment for patients with OS. In this study, we show that trabectedin (TBD), a chemotherapeutic agent approved for soft tissue sarcomas, significantly suppresses pulmonary metastasis in a mouse OS xenograft model. In vitro experiments revealed that TBD suppresses cell migration potentially by downregulating the activity of ERK1/2, intracellular molecules that are critically involved in the regulation of cell motility. Collectively, our data may provide a basis for further investigation of TBD on the potential use for OS patients who are at great risk of pulmonary metastasis.

Eribulin induces tumor vascular remodeling through intussusceptive angiogenesis in a sarcoma xenograft model.

Eribulin is a novel microtubule inhibitor that, similar to other types of microtubule inhibitors, induces apoptosis by inhibiting the mitotic division of cells. Besides this direct effect on tumor cells, previous studies have shown that eribulin has the potential to induce tumor vascular remodeling in several different cancers; however, the mechanisms underlying this phenomenon remain unclear. In the present study, we aimed to elucidate whether eribulin is effective against synovial sarcoma, a relatively rare sarcoma that often affects adolescents and young adults, and to histologically investigate the microstructure of tumor vessels after the administration of eribulin. We found that eribulin exhibits potent antitumor activity against synovial sarcoma in a tumor xenograft model and that tumor vessels frequently have intervascular pillars, a hallmark of intussusceptive angiogenesis (IA), after the administration of eribulin. IA is a distinct form of angiogenesis that is involved in normal developmental processes as well as pathological conditions. Our data indicate that IA is potentially involved in eribulin-induced vascular remodeling and thereby suggest previously unacknowledged role of IA in regulating the tumor vasculature after eribulin administration.

Incidence and Characteristics of Traumatic Shoulder Instability in Japanese Military Cadets.

Little is known regarding the incidence of the shoulder instability in Japan. The aim of this study was to evaluate the incidence of traumatic shoulder instability among Japanese military cadets. A prospective cohort study was performed to capture all traumatic shoulder instability events between 2009 and 2012 among cadets in a military educational academy of the Japan Self Defense Forces. The total number of cadets in the cohort was 5,402 (average age 20.6 years). The incidence of instability events, including dislocation or subluxation, was calculated. Chronicity, demographics of participants, mechanism of injury, and athletic events were also evaluated. The incidence of traumatic dislocation was 4.1/1,000 person-years and that of subluxation was 6.1/1,000 person-years. The incidence of primary dislocation or subluxation was 5.4/1,000 person-years and that of recurrent dislocation or subluxation was 4.7/1,000 person-years. Of first dislocations or subluxations, 92% occurred during sports activities, including after-school sports activities, military training, and gym classes. In conclusion, the overall incidence of shoulder instability events among Japanese military cadets was 10.3/1,000 person-years, and was extremely high. Most shoulder instability events occurred during sports activities, and a program to prevent such injuries during sports activities is necessary for young participants.

Ambipolar MoS2 thin flake transistors.

Field effect transistors (FETs) made of thin flake single crystals isolated from layered materials have attracted growing interest since the success of graphene. Here, we report the fabrication of an electric double layer transistor (EDLT, a FET gated by ionic liquids) using a thin flake of MoS(2), a member of the transition metal dichalcogenides, an archetypal layered material. The EDLT of the thin flake MoS(2) unambiguously displayed ambipolar operation, in contrast to its commonly known bulk property as an n-type semiconductor. High-performance transistor operation characterized by a large "ON" state conductivity in the order of ~mS and a high on/off ratio >10(2) was realized for both hole and electron transport. Hall effect measurements revealed mobility of 44 and 86 cm(2) V(-1) s(-1) for electron and hole, respectively. The hole mobility is twice the value of the electron mobility, and the density of accumulated carrier reached 1 × 10(14) cm(-2), which is 1 order of magnitude larger than conventional FETs with solid dielectrics. The high-density carriers of both holes and electrons can create metallic transport in the MoS(2) channel. The present result is not only important for device applications with new functionalities, but the method itself would also act as a protocol to study this class of material for a broader scope of possibilities in accessing their unexplored properties.