Hypothyroidism is a major manifestation of autoimmune thyroid diseases (AITD). We previously reported that a low selenium (Se) status was linked to an elevated prevalence of thyroid diseases. We ...hypothesized that Se status may also influence the restoration of thyroid function. Thus, this study aimed to investigate the factors affecting the recovery of thyroid function in patients with (sub-)clinical hypothyroidism, with a specific focus on Se status.
We conducted a 6-year prospective cohort study comparing two counties with different Se concentrations. Demographic and disease data were collected from 1,190 individuals (549 Se-adequate and 641 Se-deficient) who completed a follow-up study in 2019. In addition, urinary iodine (I) levels, thyroid function, and serum and nail Se levels were measured. Logistic regression was used to investigate the relationship between Se deficiency and recovery of thyroid function.
Sex and smoking status was similar between the two counties studied. Thyroid function recovery rate was significantly higher in Se-deficient counties (46.0% vs. 30.6%, P = 0.008). In the multivariate analysis, our results show that female sex (odds ratio OR (95% confidence interval CI) = 1.875 (1.080-3.257), P = 0.026 and increasing age OR (95%CI) = 1.028(1.007-1.049), P = 0.009 were associated with the recovery rate. Additionally, our study revealed that while Se status was significant in the univariate analysis, this association appeared to disappear in the multivariate analysis.
Female sex and increasing age have unfavorable effects on the recovery of thyroid function in patients over 30 years of age with (sub-) clinical hypothyroidism.
Although many resting state and task state characteristics have been studied, it is still unclear how the brain network switches from the resting state during tasks. The current theory shows that the ...brain is a complex dynamic system and synchrony is defined to measure brain activity. The study compared the changes of synchrony between the resting state and different task states in healthy young participants (
= 954). It also examined the ability to switch from the resting state to the task-general architecture of synchrony. We found that the synchrony increased significantly during the tasks. And the results showed that the brain has a task-general architecture of synchrony during different tasks. The main feature of task-based reasoning is that the increase in synchrony of high-order cognitive networks is significant, while the increase in synchrony of sensorimotor networks is relatively low. In addition, the high synchrony of high-order cognitive networks in the resting state can promote task switching effectively and the pre-configured participants have better cognitive performance, which shows that spontaneous brain activity and cognitive ability are closely related. These results revealed changes in the brain network configuration for switching between the resting state and task state, highlighting the consistent changes in the brain network between different tasks. Also, there was an important relationship between the switching ability and the cognitive performance.
Ginkgo biloba extract (EGb-761) has been in use to treat variety of ailments including memory loss and emotional disorders usually experienced after ischemic stroke. However, data regarding its ...protective role in stroke associated motor dysfunction is scarce.
The present work was designed to investigate the long-term effects of EGb-761 on the motor dysfunctions associated with permanent middle cerebral artery occlusion (pMCAO) in rats.
Focal ischemic stroke was induced in male Sprague–Dawley rats by pMCAO. These rats were orally administered with EGb-761 (25, 50, 100 mg/kg) and positive control butylphthalide (50 mg/kg) for up to 28 consecutive days. The motor function was evaluated by assessing neurological scores, rotarod performance and gait analysis after 7, 14, 21 and 28 days. After 28 days, the histological examination of in frontal cortex and hippocampus was also carried out.
EGb-761 treatment significantly improved motor function with better outcome in coordination and gait impairment rats. EGb-761 (25, 50, 100 mg/kg) treatment for 28 days significantly decreased the neurological scores. After 28 days of treatment EGb-761 (50 and 100 mg/kg) significantly increased the latency in rotarod test, walk speed, and the body rotation, whereas, decreased the stride time and the left posterior swing length in gait were observed. EGb-761 (50, 100 mg/kg). EGb-761 (50, 100 mg/kg) significantly improved the pathological changes related to pMCAO.
EGb 761 could improve motor function especially gait impairments among pMCAO rat model related to the decreased neuronal damage. Therefore, it might be the potential to be explored further as an effective therapeutic drug to treat post stroke motor dysfunctions.
Graphical abstract
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Sleep disturbance and executive function impairment are common in patients with major depressive disorder (MDD), though the relationship between the two remains unclear. We investigated this ...association in first-episode, treatment-naïve patients with MDD.
We analyzed data from 242 patients with MDD. We divided the patients into 2 groups based on sleep disturbance severity and compared the executive function odds ratios between the groups.
A total of 121 pairs of patients were matched (age 39.4 ± 10.1, 70.2% female). After propensity score matching, the odds ratios for cognitive impairment in patients with MDD and severe sleep disturbance were 1.922 (1.068-3.459, P = 0.029, q = 0.044) in executive functioning; 2.023 (1.211-3.379, P = 0.007, q = 0.021) in executive shifting.
Sleep disturbance is associated with executive functioning impairment in first-episode, treatment-naïve patients with MDD. Severe sleep disturbance can be a marker and aid in recognizing executive function impairment in patients with first-episode treatment-naïve MDD. Severe sleep disturbance can be a potential modifiable factor to improve executive function in MDD, as well as an effective measurement to improve cognition for sleep symptom management that should be enforced at initial treatment of first-episode MDD. Further study is required to confirm our results.
ClinicalTrials.gov: NCT02023567 ; registration date: December 2013.
Limonene, a monocyclic monoterpene, is known for its using as an important precursor of many flavoring, pharmaceutical, and biodiesel products. Currently, d-limonene has been produced via ...fractionation from essential oils or as a byproduct of orange juice production, however, considering the increasing need for limonene and a certain amount of pesticides may exist in the limonene obtained from the citrus industry, some other methods should be explored to produce limonene.
To construct the limonene synthetic pathway in
, two genes encoding neryl diphosphate synthase 1 (NDPS1) and limonene synthase (LS) were codon-optimized and heterologously expressed in
. Furthermore, to maximize limonene production, several genes involved in the MVA pathway were overexpressed, either in different copies of the same gene or in combination. Finally with the optimized pyruvic acid and dodecane concentration in flask culture, a maximum limonene titer and content of 23.56 mg/L and 1.36 mg/g DCW were achieved in the final engineered strain Po1f-LN-051, showing approximately 226-fold increase compared with the initial yield 0.006 mg/g DCW.
This is the first report on limonene biosynthesis in oleaginous yeast
by heterologous expression of codon-optimized
and
genes. To our knowledge, the limonene production 23.56 mg/L, is the highest limonene production level reported in yeast. In short, we demonstrate that
provides a compelling platform for the overproduction of limonene derivatives, and even other monoterpenes.
As the key components of wind turbine, the weight of gear transmission system becomes larger and larger with the increasing power of wind turbine. Lightweight and high reliability has been the ...developing tendency for planetary gear transmission system for working reliability and reducing costs. A coupled nonlinear dynamics modeling for planetary gear transmission system in wind turbine is established after comprehensive considering these non-linear factors associated with time-varying mesh stiffness, dynamic transmission error, gear mesh impact and input varying load. Load factors of planetary gear transmission system are induced from the coupled nonlinear dynamics modeling. Then a novel optimum design approach including lightweight and reliability as constraints is presented. The optimization results show that the reliability of original parameters is higher than that of the optimized parameters, while the volume of planetary gear transmission system can greatly be decreased with the overall system reliability requirements.
Here, we examine whether neurons differentiated from transplanted stem cells can integrate into the host neural network and function in awake animals, a goal of transplanted stem cell therapy in the ...brain. We have developed a technique in which a small “hole” is created in the inferior colliculus (IC) of rhesus monkeys, then stem cells are transplanted in situ to allow for investigation of their integration into the auditory neural network. We found that some transplanted cells differentiated into mature neurons and formed synaptic input/output connections with the host neurons. In addition, c-Fos expression increased significantly in the cells after acoustic stimulation, and multichannel recordings indicated IC specific tuning activities in response to auditory stimulation. These results suggest that the transplanted cells have the potential to functionally integrate into the host neural network.
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•Stem cells were transplanted into the inferior colliculus (IC) of rhesus monkeys•Differentiated neurons formed reciprocal anatomical connections with host neurons•Some differentiated neurons responded to auditory stimuli in an IC-specific manner•Transplanted stem cells likely integrated into host neural networks
Integration of differentiated neurons into a functioning neural network is important for the development of stem cell therapies. Wang et al. found that neurons differentiated from transplanted stem cells respond to auditory stimuli in awake monkeys after transplantation.
•The engineering of acetyl-CoA metabolism was based on genome-scale metabolic reaction network analysis.•Metabolically engineered Yarrowia lipolytica exhibited significant improvement in squalene ...production.•10 mg/g DCW of squalene was achieved in engineered Yarrowia lipolytica in YPD medium supplemented with citrate.
As a bioactive triterpenoid, squalene is widely used in the food industry, cosmetics, and pharmacology. Squalene’s major commercial sources are the liver oil of deep-sea sharks and plant oils. In this study, we focused on the enhancement of squalene biosynthesis in Yarrowia lipolytica, with particular attention to the engineering of acetyl-CoA metabolism based on genome-scale metabolic reaction network analysis. Although the overexpression of the rate-limiting endogenous ylHMG1 (3-hydroxy-3-methylglutaryl-CoA reductase gene) could improve squalene synthesis by 3.2-fold over that by the control strain, the availability of the key intracellular precursor, acetyl-CoA, was found to play a more significant role in elevating squalene production. Analysis of metabolic networks with the newly constructed genome-scale metabolic model of Y. lipolytica iYL_2.0 showed that the acetyl-CoA pool size could be increased by redirecting carbon flux of pyruvate dehydrogenation towards the ligation of acetate and CoA or the cleavage of citrate to form oxaloacetate and acetyl-CoA. The overexpression of either acetyl-CoA synthetase gene from Salmonella enterica (acs*) or the endogenous ATP citrate lyase gene (ylACL1) resulted in a more than 50% increase in the cytosolic acetyl-CoA level. Moreover, iterative chromosomal integration of the ylHMG1, asc*, and ylACL1 genes resulted in a significant improvement in squalene production (16.4-fold increase in squalene content over that in the control strain). We also found that supplementation with 10 mM citrate in a flask culture further enhanced squalene production to 10 mg/g DCW. The information obtained in this study demonstrates that rationally engineering acetyl-CoA metabolism to ensure the supply of this key metabolic precursor is an efficient strategy for the enhancement of squalene biosynthesis.
Objective:
Curcumae Rhizoma
–
Sparganii Rhizoma
(CR-SR) is a traditional botanical drug pair that can promote blood circulation, remove blood stasis, and treat tumors in clinics. The aim of the ...present study was to investigate the therapeutic material basis and potential mechanisms of CR-SR, CR, and SR for the treatment of liver cancer.
Method:
The chemical profile analyses of CR-SR, CR, and SR were performed by molecular networking and UPLC-LTQ-Orbitrap MS
n
. The anti-liver cancer activities of CR-SR, CR, and SR were assessed by using a zebrafish xenograft model
in vivo
for the first time and detected by the HepG2 cell model
in vitro
. Combining the network analysis and molecular docking, real-time quantitative polymerase chain reaction (RT-qPCR) experiments were undertaken to further explore the mechanisms of CR-SR, CR, and SR for the treatment of liver cancer.
Results:
In total, 65 components were identified in CR-SR, CR, and SR. Based on the clusters of molecular networking, a total of 12 novel diarylheptanoids were identified from CR-SR and CR. By combining our results with information from the literature, 32 sesquiterpenoids and 21 cyclic dipeptides were identified from CR-SR, CR, and SR. The anti-liver cancer activities were observed in both the drug pair and the single botanical drugs
in vitro
and
in vivo
, and the order of activity was CR-SR > CR > SR. They could downregulate the expression of proto-oncogene tyrosine-protein kinase Src (SRC), epidermal growth factor receptor (EGFR), estrogen receptor-α (ESR1), prostaglandin endoperoxide synthase 2 (PTGS2), and amyloid precursor protein (APP).
Conclusion:
Taken together, the present study provided an experimental basis for the therapeutic material basis and potential molecular mechanisms of CR-SR, CR, and SR. This study provided a novel insight for objective clinical treatment of liver cancer.
Hantaan virus (HTNV) is a pathogenic orthohantavirus prevalent in East Asia that is known to cause hemorrhagic fever with severe renal syndrome (HFRS), which has a high fatality rate. However, a Food ...and Drug Administration (FDA)-approved vaccine is not currently available against this virus. Although inactivated vaccines have been certified and used in endemic regions for decades, the neutralizing antibody (NAb) titer induced by inactivated vaccines is low and the immunization schedule is complicated, requiring at least three injections spanning approximately 6 months to 1 year. Replication-competent vesicular stomatitis virus (VSV)-based vaccines provide prolonged protection after a single injection. In this study, we successfully engineered the HTNV glycoprotein (GP) in the VSV genome by replacing the VSV-G open reading frame. The resulting recombinant (r) rVSV-HTNV-GP was rescued, and the immunogenicity of GP was similar to that of HTNV. BALB/c mice immunized with rVSV-HTNV-GP showed a high titer of NAb against HTNV after a single injection. Notably, the cross-reactive NAb response induced by rVSV-HTNV-GP against Seoul virus (an orthohantavirus) was higher than that induced by three sequential injections of inactivated vaccines. Upon challenge with HTNV, rVSV-HTNV-GP-immunized mice showed a profoundly reduced viral burden in multiple tissues, and inflammation in the lungs and liver was nearly undetectable. Moreover, a single injection of rVSV-HTNV-GP established a prolonged immunological memory status as the NAbs were sustained for over 1 year and provided long-term protection against HTNV infection. The findings of our study can support further development of an rVSV-HTNV-GP-based HTNV vaccine with a simplified immunization schedule.
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