Reference intervals for thyroid hormones for the elderly population and their influence on the diagnosis of subclinical hypothyroidism

Background: This study aims to establish reference intervals (RIs) for thyroid hormones in the elderly population and analyze their influence on the prevalence of subclinical hypothyroidism. Methods: Thyroid hormone records of subjects who underwent routine health checkup at our hospital between 2018 and 2020 were analyzed. Thyroid stimulating hormone (TSH), total triiodothyronine, total thyroxine, free triiodothyronine (FT3), and free thyroxine (FT4) levels were compared between young and elderly subjects. Thresholds of these thyroid hormones were established for elderly subjects. Results: A total of 22,207 subjects were included. Of them, 2,254 (10.15%) were aged ≥ 65 years. Elderly subjects had higher TSH, and lower FT3 and FT4 levels when compared with young subjects. In the elderly group, the RIs for TSH, FT3 and FT4 were 0.55-5.14 mIU/L, 3.68-5.47 pmol/L, and 12.00-19.87 pmol/L, respectively. The age and sex specific RIs for TSH were 0.56-5.07 mIU/L for men and 0.51-5.25 mIU/L for women. With whole-group RIs and age and sex-specific RIs for elderly people, the prevalence of subclinical hypothyroidism was 9.83% and 6.29% (p < 0.001), respectively. Conclusions: Elderly individuals had higher TSH levels than young individuals. Our study indicated that establishing specific RIs for elderly individuals is needed. This has implications for the diagnosis and management of subclinical hypothyroidism in the elderly population

The pharmacokinetic and residue depletion study of eugenol in carp (Cyprinus carpio)

IntroductionThe pharmacokinetic profile and residue depletion of eugenol in carp (Cyprinus carpio) tissues and plasma were performed by a convenient and reliable high-performance liquid chromatography (HPLC) method.MethodsThe eugenol in carp tissues and plasma was extracted with a mixed solution of acetonitrile and methanol. N-hexane was used to remove lipid impurities. The method was successfully applied to the pharmacokinetic and residue elimination of eugenol in carp after the carp was administered a medicated bath.ResultsThe average recoveries of eugenol in tissues and plasma fortified with four concentration levels were 69.0–106.6% and 80.0–86.7%, respectively. The relative standard deviations were &lt; 8.9%. The limit of detection (LOD) was 0.01 μg/g in tissue and 0.008 μg/ml in plasma, respectively. The pharmacokinetic parameter of Cmax for eugenol in plasma at the concentrations of 20, 35, and 75 mg/L were 10.86, 17.21, and 37.32 mg/L, respectively. The t1/2 values were 3.68, 4.22, and 9.31 h. After the investigation of the anesthetic effect, 35 mg/L of eugenol was the optimal concentration for anesthesia. The highest accumulation concentration of eugenol in carp is in the liver and the lowest is in the muscle. In addition, the eugenol in tissue was eliminated rapidly and at a lower level than the LOD at 48 h. According to the residue elimination, the withdrawal time of eugenol was suggested at 5.2 days.DiscussionThese results indicate that the developed method had good linearity and accuracy, and is sensitive enough for the monitoring of eugenol residue in carp. The half-life of eugenol decreased with the increase in drug concentration and the eugenol was eliminated rapidly in carp tissues. 35 mg/L eugenol was recommended as an anesthetic in carp due to its favorable anesthetic effect and no mortality. This study will contribute to the establishment of MRL regulation and setting a withdrawal period

Research progress of abnormal lactate metabolism and lactate modification in immunotherapy of hepatocellular carcinoma

Tumors meet their energy, biosynthesis, and redox demands through metabolic reprogramming. This metabolic abnormality results in elevated levels of metabolites, particularly lactate, in the tumor microenvironment. Immune cell reprogramming and cellular plasticity mediated by lactate and lactylation increase immunosuppression in the tumor microenvironment and are emerging as key factors in regulating tumor development, metastasis, and the effectiveness of immunotherapies such as immune checkpoint inhibitors. Reprogramming of glucose metabolism and the “Warburg effect” in hepatocellular carcinoma (HCC) lead to the massive production and accumulation of lactate, so lactate modification in tumor tissue is likely to be abnormal as well. This article reviews the immune regulation of abnormal lactate metabolism and lactate modification in hepatocellular carcinoma and the therapeutic strategy of targeting lactate-immunotherapy, which will help to better guide the medication and treatment of patients with hepatocellular carcinoma

Association Analysis and Identification of ZmHKT1;5 Variation With Salt-Stress Tolerance

The high-affinity potassium transporter (HKT) genes are essential for plant salt stress tolerance. However, there were limited studies on HKTs in maize (Zea mays), and it is basically unknown whether natural sequence variations in these genes are associated with the phenotypic variability of salt tolerance. Here, the characterization of ZmHKT1;5 was reported. Under salt stress, ZmHKT1;5 expression increased strongly in salt-tolerant inbred lines, which accompanied a better-balanced Na+/K+ ratio and preferable plant growth. The association between sequence variations in ZmHKT1;5 and salt tolerance was evaluated in a diverse population comprising 54 maize varieties from different maize production regions of China. Two SNPs (A134G and A511G) in the coding region of ZmHKT1;5 were significantly associated with different salt tolerance levels in maize varieties. In addition, the favorable allele of ZmHKT1; 5 identified in salt tolerant maize varieties effectively endowed plant salt tolerance. Transgenic tobacco plants of overexpressing the favorable allele displayed enhanced tolerance to salt stress better than overexpressing the wild type ZmHKT1;5. Our research showed that ZmHKT1;5 expression could effectively enhance salt tolerance by maintaining an optimal Na+/K+ balance and increasing the antioxidant activity that keeps reactive oxygen species (ROS) at a low accumulation level. Especially, the two SNPs in ZmHKT1;5 might be related with new amino acid residues to confer salt tolerance in maize.Key Message: Two SNPs of ZmHKT1;5 related with salt tolerance were identified by association analysis. Overexpressing ZmHKT1;5 in tobaccos showed that the SNPs might enhance its ability to regulating Na+/K+ homeostasis

Gastrodin Rescues Autistic-Like Phenotypes in Valproic Acid-Induced Animal Model

Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized by impaired social interaction, restricted/repetitive behavior, and anxiety. GABAergic dysfunction has been postulated to underlie these autistic symptoms. Gastrodin is widely used clinically in the treatment of neurological disorders and showed to modulate GABAergic signaling in the animal brain. The present study aimed to determine whether treatment with gastrodin can rescue valproic acid (VPA) induced autistic-like phenotypes, and to determine its possible mechanism of action. Our results showed that administration of gastrodin effectively alleviated the autistic-associated behavioral abnormalities as reflected by an increase in social interaction and decrement in repetitive/stereotyped behavior and anxiety in mice as compared to those in untreated animals. Remarkably, the amelioration in autistic-like phenotypes was accompanied by the restoration of inhibitory synaptic transmission, α5 GABAA receptor, and type 1 GABA transporter (GAT1) expression in the basolateral amygdala (BLA) of VPA-treated mice. These findings indicate that gastrodin may alleviate the autistic symptoms caused by VPA through regulating GABAergic synaptic transmission, suggesting that gastrodin may be a potential therapeutic target in autism

Self-employment gap between natives and immigrants in Sweden

This paper examines three questions orderly with the help of the European Social Survey (ESS) pooled cross section data. Firstly, whether there is a gap of probability of being self-employed existed between natives and immigrants in Sweden. Secondly, whether there is heterogeneity existed within different ethnic group of immigrants and thirdly, if that heterogeneity existed across genders. The results show that there is no significant gap of probability of being self-employed between natives and immigrants in Sweden, and it can be due to the heterogeneity within the immigrant group itself. The results of logit model indicate that the probability of being self-employed for immigrants from Asian countries (the Middle East countries excluded) are significantly different from Swedish natives, and that for immigrants from the Middle East countries and Asian countries (the Middle East countries excluded) are both significantly different from immigrants from the Nordic countries (Sweden excluded). Furthermore, when looking by the perspective of genders, the results reveal that the heterogeneity existed when examining the groups for both genders can only be found in male immigrant group, while female immigrant group do not appear to be heterogeneous

Gradient phonemic contrast in Nanjing Mandarin

Sounds that are contrastive in a language are rated by listeners as being more differentfrom each other than sounds that don’t occur in the language or sounds that areallophones of a single phoneme. The study reported in this paper replicates this findingand adds new data on the perceptual impact of learning a language with a new contrast.Two groups of speakers of the Nanjing dialect of Mandarin Chinese were tested. Onegroup was older and had not been required to learn standard Mandarin as school children,while the other younger group had learned standard Mandarin in school. Nanjing dialectdoes not contrast [n] and [l], while standard Mandarin does. Listeners rated the similarityof naturally produced non-words presented in pairs, where the only difference betweenthe tokens was the medial consonant. Pairs contrasting [n] and [l] were rated by olderNanjing speakers as if two [n] tokens or two [l] tokens had been presented, while thesesame pairs were rated by younger Nanjing speakers as noticeably different but not asdifferent as pairs that contrast in their native language

Computational optimization of the internal cooling passages of a guide vane by a gradient-based algorithm

To keep the spatially averaged temperature and thermal stress of gas turbine blades and guide vanes within a permissible level, the present research concentrates on the optimization of the internal cooling passages in a guide vane. The main purpose is to search for the most optimal sizes, distributions, and shapes of internal cooling channels located in a guide vane. Cylindrical cooling passages and newly built passages shaped by Bezier curves are both considered in this investigation. In order to maintain the shapes of the cooling channels within the scale of the vane profile, a new technique is suggested to discretize the vane into the components, and then the outline of the passages is built based on the components. The optimization of sizes, locations, and shapes of the cooling passages is solved as a single-objective problem using a gradient-based optimization algorithm, i.e., the globally convergent method of moving asymptotes (GCMMA). The optimized result displays a substantial reduction in both the spatially averaged temperature and thermal stress of the vane, and the related configurations are included and discussed in the investigation