The Evolutionarily Conserved LIM Homeodomain Protein LIM-4/LHX6 Specifies the Terminal Identity of a Cholinergic and Peptidergic C. elegans Sensory/Inter/Motor Neuron-Type

The expression of specific transcription factors determines the differentiated features of postmitotic neurons. However, the mechanism by which specific molecules determine neuronal cell fate and the extent to which the functions of transcription factors are conserved in evolution are not fully understood. In C. elegans, the cholinergic and peptidergic SMB sensory/inter/motor neurons innervate muscle quadrants in the head and control the amplitude of sinusoidal movement. Here we show that the LIM homeobox protein LIM-4 determines neuronal characteristics of the SMB neurons. In lim-4 mutant animals, expression of terminal differentiation genes, such as the cholinergic gene battery and the flp-12 neuropeptide gene, is completely abolished and thus the function of the SMB neurons is compromised. LIM-4 activity promotes SMB identity by directly regulating the expression of the SMB marker genes via a distinct cis-regulatory motif. Two human LIM-4 orthologs, LHX6 and LHX8, functionally substitute for LIM-4 in C. elegans. Furthermore, C. elegans LIM-4 or human LHX6 can induce cholinergic and peptidergic characteristics in the human neuronal cell lines. Our results indicate that the evolutionarily conserved LIM-4/LHX6 homeodomain proteins function in generation of precise neuronal subtypes

FOXO protects against age‐progressive axonal degeneration

Summary Neurodegeneration resulting in cognitive and motor impairment is an inevitable consequence of aging. Little is known about the genetic regulation of this process despite its overriding importance in normal aging. Here, we identify the Forkhead Box O (FOXO) transcription factor 1, 3, and 4 isoforms as a guardian of neuronal integrity by inhibiting age‐progressive axonal degeneration in mammals. FOXO expression progressively increased in aging human and mouse brains. The nervous system‐specific deletion of Foxo transcription factors in mice accelerates aging‐related axonal tract degeneration, which is followed by motor dysfunction. This accelerated neurodegeneration is accompanied by levels of white matter astrogliosis and microgliosis in middle‐aged Foxo knockout mice that are typically only observed in very old wild‐type mice and other aged mammals, including humans. Mechanistically, axonal degeneration in nerve‐specific Foxo knockout mice is associated with elevated mTORC1 activity and accompanying proteotoxic stress due to decreased Sestrin3 expression. Inhibition of mTORC1 by rapamycin treatment mimics FOXO action and prevented axonal degeneration in Foxo knockout mice with accelerated nervous system aging. Defining this central role for FOXO in neuroprotection during mammalian aging offers an invaluable window into the aging process itself

Comparison of the outcomes between sorafenib and lenvatinib as the first-line systemic treatment for HBV-associated hepatocellular carcinoma: a propensity score matching analysis

In a randomized controlled trial, lenvatinib was non-inferior to sorafenib in overall survival (OS) of patients with unresectable hepatocellular carcinoma (uHCC). This study aimed to compare the effects of sorafenib and lenvatinib as first-line systemic therapy against uHCC with real-world data in chronic hepatitis B patients. This retrospective single-center study involved 132 patients with HBV-related uHCC. Propensity score matching (PSM) was used to balance the baseline characteristics, including age, sex, serum alpha-fetoprotein levels, Child–Pugh class, tumor size, and tumor stage. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), time to progression (TTP), and tumor response. After PSM, the final analysis included 44 patients treated with lenvatinib and 88 with sorafenib. The OS (7.0 vs 9.2months, p = 0.070) and PFS (4.6 vs 2.4months, p = 0.134) were comparable between the two drugs. Multivariable analysis showed that lenvatinib and sorafenib were not independent prognostic factors of OS (adjusted hazard ratio = 1.41, 95% confidence interval = 0.96–2.08, p = 0.077) after adjustment for baseline alpha-fetoprotein levels, total bilirubin levels, alanine aminotransferase level, performance status, tumor stage, and tumor size. However, the lenvatinib group had a significantly prolonged TTP (5.2 vs 2.5months, p = 0.018) and a higher objective response rate (18.2% vs 4.5%, p = 0.020) and disease control rate (77.3% vs 47.7%, p = 0.001) than the sorafenib group. Our study demonstrated that lenvatinib had a comparable OS and PFS but longer TTP and better tumor response compared to sorafenib in patients with HBV-related uHCC

예쁜 꼬마선충을 이용한 자기수용감각기 TRPC 채널의 기능과 자기수용감각신경의 기작 연구

prohibitionDoctordCollectio

New Synthetic Operon Vectors for Expressing Multiple Proteins in the Chlamydomonas reinhardtii Chloroplast

Microalgae are a promising platform for generating valuable commercial products, including proteins that may not express well in more traditional cell culture systems. In the model green alga Chlamydomonas reinhardtii, transgenic proteins can be expressed from either the nuclear or chloroplast genome. Expression in the chloroplast has several advantages, but technology is not yet well developed for expressing multiple transgenic proteins simultaneously. Here, we developed new synthetic operon vectors to express multiple proteins from a single chloroplast transcription unit. We modified an existing chloroplast expression vector to contain intercistronic elements derived from cyanobacterial and tobacco operons and tested the ability of the resulting operon vectors to express two or three different proteins at a time. All operons containing two of the coding sequences (for C. reinhardtii FBP1 and atpB) expressed the products of those genes, but operons containing the other two coding sequences (C. reinhardtii FBA1 and the synthetic camelid antibody gene VHH) did not. These results expand the repertoire of intercistronic spacers that can function in the C. reinhardtii chloroplast, but they also suggest that some coding sequences do not function well in the context of synthetic operons in this alga

New Synthetic Operon Vectors for Expressing Multiple Proteins in the <i>Chlamydomonas reinhardtii</i> Chloroplast

Microalgae are a promising platform for generating valuable commercial products, including proteins that may not express well in more traditional cell culture systems. In the model green alga Chlamydomonas reinhardtii, transgenic proteins can be expressed from either the nuclear or chloroplast genome. Expression in the chloroplast has several advantages, but technology is not yet well developed for expressing multiple transgenic proteins simultaneously. Here, we developed new synthetic operon vectors to express multiple proteins from a single chloroplast transcription unit. We modified an existing chloroplast expression vector to contain intercistronic elements derived from cyanobacterial and tobacco operons and tested the ability of the resulting operon vectors to express two or three different proteins at a time. All operons containing two of the coding sequences (for C. reinhardtii FBP1 and atpB) expressed the products of those genes, but operons containing the other two coding sequences (C. reinhardtii FBA1 and the synthetic camelid antibody gene VHH) did not. These results expand the repertoire of intercistronic spacers that can function in the C. reinhardtii chloroplast, but they also suggest that some coding sequences do not function well in the context of synthetic operons in this alga

New Reliability Criteria for Korean Workers’ Health Examination Spirometry Results

The Occupational Safety and Health Research Institute is currently evaluating spirometry tests used for worker health examinations by applying the 2005 American Thoracic Society (ATS) and European Respiratory Society (ERS) spirometric test standardization guide and reviewing the application of the 2019 ATS/ERS guide. To compare results obtained using the new evaluation criteria with previous results and determine whether it is appropriate to apply them to Korean workers’ health examinations, we reviewed spirometry results from 325 special health examination institutions. Although evaluation criteria such as extrapolation volume, correction error, and forced inspiratory vital capacity were applied more strictly, institutions had higher reliability scores. Primarily because the acceptability and repeatability of forced expiratory volume in 1 second and forced vital capacity were judged separately, and thus, deduction width was reduced. The study shows that adopting the new evaluation criteria would reduce the possible use of inappropriate data, increase tester and doctor understanding of result selection and interpretation, increase result reliability, and reduce the testing burden

Sex-Specific Association between Sodium Intake Estimated by 24-Hour Urinary Sodium Excretion and Nonalcoholic Fatty Liver Disease: The Community-Based Prospective Cohort Study

Evidence for the association between high sodium intake and the onset of nonalcoholic fatty liver disease (NAFLD) is insufficient. This study examined the sex-specific association between sodium intake and the risk of NAFLD. This study included 2582 adults (aged 40–69 years; 1011 males and 1571 females). The total sodium excreted over 24 h was estimated from spot urine specimens using Tanaka’s equation. Based on these estimates, participants were categorized into three groups according to their 24-h urinary sodium excretion levels: lowest (T1), middle (T2), and highest (T3). In addition, the participants were divided into non-NAFLD (≤36) and NAFLD (>36) groups based on the hepatic steatosis index. During the follow-up period (14 years), NAFLD was observed in 551 participants. The estimated 24-h urinary sodium excretion levels were positively associated with the incidence of NAFLD in all subjects. Upon sex stratification, females in the T2 and T3 groups exhibited adjusted hazard ratios of 1.35 and 1.51, respectively, compared with the T1 group. However, a significant relationship was not observed in males. High intake of sodium, especially among females, may be an important factor contributing to the development of NAFLD. Individuals with high sodium intake should be appropriately counselled and monitored for the risk of NAFLD

Development of a Column-Switching HPLC-MS/MS Method and Clinical Application for Determination of Ethyl Glucuronide in Hair in Conjunction with AUDIT for Detecting High-Risk Alcohol Consumption

It is critical to assess the severity of alcohol consumption in certain diseases such as alcohol liver disease and alcohol addiction. Ethyl glucuronide (EtG) is a highly stable metabolite of ethanol in hair; thus, it was proposed as a long-term monitoring marker for alcohol consumption. Therefore, an HPLC-MS/MS method for EtG in hair was developed and applied to a clinical setting to assess the relevance of the EtG concentration and/or the Alcohol Use Disorders Identification Test (AUDIT) score to high-risk alcohol consumption. EtG was extracted from 10 mg of hair using water and analyzed using on-line sample purification coupled to HPLC-MS/MS. The diagnostic performances of the EtG concentration and/or the AUDIT score for detecting high-risk alcohol consumption were statistically evaluated between alcohol addicts (n = 44) and average alcohol users (n = 19). The on-line sample purification resulted in labor-saving with smaller sample amount. Both the EtG concentrations (4.0&ndash;587.4 pg/mg vs. 12.9&ndash;74.9 pg/mg) and the AUDIT scores (4&ndash;40 vs. 5&ndash;28) obtained from the alcohol addicts were significantly higher than those from the average alcohol users. The performance evaluation demonstrated that the integration score of the EtG concentration and the AUDIT score increased diagnostic performance for high-risk alcohol consumption

Associations of Sarcopenia and Sarcopenic Obesity With Metabolic Syndrome Considering Both Muscle Mass and Muscle Strength

Objectives: We investigated the associations of sarcopenia-defined both in terms of muscle mass and muscle strength-and sarcopenic obesity with metabolic syndrome. Methods: Secondary data pertaining to 309 subjects (85 men and 224 women) were collected from participants in exercise programs at a health center in a suburban area. Muscle mass was measured using bioelectrical impedance analysis, and muscle strength was measured via handgrip strength. Sarcopenia based on muscle mass alone was defined as a weight-adjusted skeletal muscle mass index more than two standard deviations below the mean of a sex-specific young reference group (class II sarcopenia). Two cut-off values for low handgrip strength were used: the first criteria were <26 kg for men and <18 kg for women, and the second criteria were the lowest quintile of handgrip strength among the study subjects. Sarcopenic obesity was defined as the combination of class II sarcopenia and being in the two highest quintiles of total body fat percentage among the subjects. The associations of sarcopenia and sarcopenic obesity with metabolic syndrome were evaluated using logistic regression models. Results: The age-adjusted risk ratios (RRs) of metabolic syndrome being compared in people with or without sarcopenia defined in terms of muscle mass were 1.25 (95% confidence interval [CI], 1.06 to 1.47, p=0.008) in men and 1.12 (95% CI, 1.06 to 1.19, p<0.001) in women, which were found to be statistically significant relationships. The RRs of metabolic syndrome being compared in people with or without sarcopenic obesity were 1.31 in men (95% CI, 1.10 to 1.56, p=0.003) and 1.17 in women (95% CI, 1.10 to 1.25, p<0.001), which were likewise found to be statistically significant relationships. Conclusions: The associations of sarcopenia defined in terms of muscle mass and sarcopenic obesity with metabolic syndrome were statistically significant in both men and women. Therefore, sarcopenia and sarcopenic obesity must be considered as part of the community-based management of non-communicable diseases