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This experiment was conducted to evaluate the impact of substituting rice straw with citrus pulp (CRP), sweet potato peels (SPP) and vines (SPV) on fermentation quality and in vitro digestibility when ensiled with or without wet brewers' grains (WBG). Seven treatments were set as follows: (i) rice straw only (control); (ii) 800 g rice straw/kg + 200 g CRP/kg (RC); (iii) 720 g rice straw/kg + 180 g CRP/kg + 100 g WBG/kg (RC+); (iv) 800 g rice straw/kg + 200 g SPP/kg (RP); (v) 720 g rice straw + 180 g SPP/kg + 100 g WBG/kg (RP+); (vi) 800 g rice straw/kg + 200 g SPV/kg (RV); (vii) 720 g rice straw/kg + 180 g SPV/kg + 100 g WBG/kg (RV+). After ensiling for 3, 7, 14, 30 and 60 days, silos were opened for fermentation profile, aerobic stability and in vitro parameter analyses. All substitution types improved fermentation quality, characterized by significantly lower pH and NH3-N content, higher lactic acid content and V-scores. WBG application promoted hetero-fermentation and significantly increased DM losses, acetic acid and ethanol contents. After 60 days of ensiling, the NDF, ADF and cellulose contents in mixed silages significantly decreased compared to control. During aerobic exposure, WBG application significantly prolonged aerobic stability. SPV substitution significantly improved in vitro digestibility of dry matter, NDF and ADF. In conclusion, the SPP substitution combined with WBG application was recommended as a result of the optimal balance of fermentation quality, aerobic stability and in vitro digestibility.
Fossil feathers have greatly improved our understanding of the evolutionary transition from non-avian dinosaurs to birds and the evolution of feathers, and may be the only evidence for their source animals in the fossil record. Hot spring environments have been demonstrated to be conducive to the preservation of fossils, but internal silicification of feathers was not observed in the only avian carcass so far discovered in ancient hot spring deposits. To determine whether feathers can be internally silicified, here we analyse feathers sampled from a modern hot spring vent pool – Champagne Pool – in New Zealand. Our results of scanning electron microscopy (SEM)-energy dispersive X-ray spectrometry elemental mapping show that the sampled feathers are silicified to different degrees, and one of them is pervasively silicified. SEM observations show that feathers can be silicified at the cellular level. Degradation is involved in the silicification of feathers, as indicated by the reduction of the abundance of carbon and the loss of keratin fibrils. Our findings suggest that ancient deposits of hot spring vent pools are promising targets in search for fossil feathers.
Grey matter (GM) reduction is a consistent observation in established late stages of schizophrenia, but patients in the untreated early stages of illness display an increase as well as a decrease in GM distribution relative to healthy controls (HC). The relative excess of GM may indicate putative compensatory responses, though to date its relevance is unclear.
343 first-episode treatment-naïve patients with schizophrenia (FES) and 342 HC were recruited. Multivariate source-based morphometry was performed to identify covarying ‘networks' of grey matter concentration (GMC). Neurocognitive scores using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and symptom burden using the Positive and Negative Symptoms Scale (PANSS) were obtained. Bivariate linear relationships between GMC and cognition/symptoms were studied.
Compared to healthy subjects, FES had prominently lower GMC in two components; the first consists of the anterior insula, inferior frontal gyrus, anterior cingulate and the second component with the superior temporal gyrus, precuneus, inferior/superior parietal lobule, cuneus, and lingual gyrus. Higher GMC was seen in adjacent areas of the middle and superior temporal gyrus, middle frontal gyrus, inferior parietal cortex and putamen. Greater GMC of this component was associated with lower duration of untreated psychosis, less severe positive symptoms and better performance on cognitive tests.
In untreated stages of schizophrenia, both a distributed lower and higher GMC is observable. While the higher GMC is relatively modest, it occurs across frontoparietal, temporal and subcortical regions in association with reduced illness burden suggesting a compensatory role for higher GMC in the early stages of schizophrenia.
Ebselen is a well-known synthetic compound mimicking glutathione peroxidase (GPx), which catalyses some vital reactions that protect against oxidative damage. Based on a large number of in vivo and in vitro studies, various mechanisms have been proposed to explain its actions on multiple targets. It targets thiol-related compounds, including cysteine, glutathione, and thiol proteins (e.g., thioredoxin and thioredoxin reductase). Owing to this, ebselen is a unique multifunctional agent with important effects on inflammation, apoptosis, oxidative stress, cell differentiation, immune regulation and neurodegenerative disease, with anti-microbial, detoxifying and anti-tumour activity. This review summarises the current understanding of the multiple biological processes and molecules targeted by ebselen, and its pharmacological applications.
Deficits in event-related potential (ERP) including duration mismatch negativity (MMN) and P3a have been demonstrated widely in chronic schizophrenia (SZ) but inconsistent findings were reported in first-episode patients. Psychotropic medications and diagnosis might contribute to different findings on MMN/P3a ERP in first-episode patients. The present study examined MMN and P3a in first episode drug naïve SZ and bipolar disorder (BPD) patients and explored the relationships among ERPs, neurocognition and global functioning.
Twenty SZ, 24 BPD and 49 age and sex-matched healthy controls were enrolled in this study. Data of clinical symptoms [Positive and Negative Symptoms Scale (PANSS), Young Manic Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD)], neurocognition [Wechsler Adult Intelligence Scale (WAIS), Cattell's Culture Fair Intelligence Test (CCFT), Delay Matching to Sample (DMS), Rapid Visual Information Processing (RVP)], and functioning [Functioning Assessment Short Test (FAST)] were collected. P3a and MMN were elicited using a passive auditory oddball paradigm.
Significant MMN and P3a deficits and impaired neurocognition were found in both SZ and BPD patients. In SZ, MMN was significantly correlated with FAST (r = 0.48) and CCFT (r = −0.31). In BPD, MMN was significantly correlated with DMS (r = −0.54). For P3a, RVP and FAST scores were significant predictors in SZ, whereas RVP, WAIS and FAST were significant predictors in BPD.
The present study found deficits in MMN, P3a, neurocognition in drug naïve SZ and BPD patients. These deficits appeared to link with levels of higher-order cognition and functioning.
The Jueluotage area, which is located in the southern branch of the Eastern Tianshan and northeast of the Tarim Basin, represents a vital locality for investigating intracontinental reactivation induced by the tectonic events at the Eurasian plate margin. This study applies zircon and apatite (U–Th)/He and apatite fission-track thermochronology to the Jueluotage area in the Eastern Tianshan. Our data and thermal history modelling show that the Jueluotage area experienced Triassic–Early Jurassic (˜240–180 Ma) cooling, reflecting the closure of the North Tianshan Ocean and subsequent far-field effects of collision/accretion of the Qiangtang Block and Kunlun terrane. Following this period of fast cooling, a differential exhumation process occurred between the various tectonic belts in the Jueluotage area. The Aqishan–Yamansu belt was exposed at the surface during the Triassic–Early Jurassic cooling phase and experienced subsequent burial, which continued until Early Cretaceous time when a pulse of exhumation occurred. However, the major fault zones (Kanggurtag ductile shear zone and Aqikkuduk Fault) and Central Tianshan arc have remained tectonically stable since Early Jurassic time. No Cenozoic rapid cooling was recorded by the low-temperature thermochronology results in this study, indicating that much of the Jueluotage area was exhumed to the upper crust in the late Mesozoic period.
Type D personality and depression are the independent psychological risk factors for adverse outcomes in cardiovascular patients. The aim of this study was to examine the combined effect of Type D personality and depression on clinical outcomes in patients suffering from acute myocardial infarction (AMI).
This prospective cohort study included 3568 patients diagnosed with AMI between February 2017 and September 2018. Type D personality and depression were assessed at baseline, while the major adverse cardiac event (MACE) rate (cardiac death, recurrent non-fatal myocardial infarction, revascularization, and stroke) and in-stent restenosis (ISR) rate were analyzed after a 2-year follow-up period.
A total of 437 patients developed MACEs and 185 had ISR during the follow-up period. The Type D (+) depression (+) and Type D (+) depression (−) groups had a higher risk of MACE [95% confidence interval (CI) 1.74–6.07] (95% CI 1.25–2.96) and ISR (95% CI 3.09–8.28) (95% CI 1.85–6.22). Analysis of Type D and depression as continuous variables indicated that the main effect of Type D, depression and their combined effect were significantly associated with MACE and ISR. Moreover, Type D (+) depression (+) and Type D (+) depression (−) emerged as significant risk factors for MACE and ISR in males, while only Type D (+) depression (+) was associated with MACE and ISR in female patients.
These findings suggest that patients complicated with depression and Type D personality are at a higher risk of adverse cardiovascular outcomes. Individual assessments of Type D personality and depression, and comprehensive interventions are required.
Seasonal climate variability is an important component of Earth's climate system, and has a significant impact on ecosystems and social systems. However, the temporal resolution of most proxy-based paleoclimate records is limiting to fully understand the past seasonal changes. Here, we used high-precision monthly resolution Sr/Ca records of three Tridacna squamosa specimens from the northern South China Sea (SCS) to reconstruct the sea surface temperature (SST) seasonality during three time periods from the middle Holocene. The results suggested that SST seasonality in the northern SCS during the middle Holocene (3.21 ± 0.98°C) was smaller than that for recent decades (AD 1994–2004, 4.32 ± 0.59°C). Analysis of modern instrumental data showed that the SST seasonality in the northern SCS was dominated by the winter SST, which was deeply influenced by the intensity of East Asian winter monsoon (EAWM). A strong EAWM usually resulted in cooler winter SST and a larger SST seasonality in the northern SCS. The reconstructed Holocene EAWM records showed that the EAWM strengthened from the middle to late Holocene, which was seen in our reconstruction of less SST seasonality changes during the middle Holocene in the northern SCS. This study highlighted that the Sr/Ca ratios from Tridacna shells can be used as a potential high-resolution indicator of past seasonal climate changes.
The study was conducted to determine the effects of three dietary Se sources, such as sodium-selenite (S-S), seleno-yeast (S-Y) and seleno-methionine (S-M), on Se concentration, glutathione peroxidase (GPX) and TXNRD activities, and mRNA expression of fifteen representative selenoproteins, and protein expression of four endoplasmic reticulum-resided selenoproteins in a wide range of tissues of yellow catfish. Compared with S-S and S-M groups, dietary S-Y significantly decreased growth performance and feed utilisation of yellow catfish. Dietary Se sources significantly influenced Se contents in the spleen, dorsal muscle and the kidney, GPX activities in spleen, kidney, intestine, muscle and mesenteric fat, and TXNRD activities in the heart, intestine and mesenteric fat. Among ten tested tissues, dietary Se sources influenced mRNA expression of GPX4 and SELENOK in three tissues; GPX3, SELENOS and TXNRD2 in four tissues; SELENOF, SELENON and DIO2 in five tissues; SELENOM, GPX1/2 and TXNRD3 in six tissues; SELENOW in seven tissue and SELENOP and SELENOT in eight tissues. Based on these observations above, S-S and S-M seem to be suitable Se sources for improving growth performance and feed utilisation of yellow catfish. Dietary Se sources differentially influence the expression of selenoproteins in various tissues of yellow catfish. For the first time, we determined the expression of selenoproteins in fish in responses to dietary Se sources, which contributes to a better understanding of the functions and regulatory mechanisms of selenoporteins.
Coronavirus disease 2019 (COVID-19) is a newly emerged disease with various clinical manifestations and imaging features. The diagnosis of COVID-19 depends on a positive nucleic acid amplification test by real-time reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the clinical manifestations and imaging features of COVID-19 are non-specific, and nucleic acid test for SARS-CoV-2 can have false-negative results. It is presently believed that detection of specific antibodies to SARS-CoV-2 is an effective screening and diagnostic indicator for SARS-CoV-2 infection. Thus, a combination of nucleic acid and specific antibody tests for SARS-CoV-2 will be more effective to diagnose COVID-19, especially to exclude suspected cases.
In present study, we explored the effects and the underlying mechanisms of phospholipase C (PLC) mediating glucose-induced changes in intestinal glucose transport and lipid metabolism by using U-73122 (a PLC inhibitor). We found that glucose incubation activated the PLC signal and U-73122 pre-incubation alleviated the glucose-induced increase in plcb2, plce1 and plcg1 mRNA expression. Meanwhile, U-73122 pre-treatment blunted the glucose-induced increase in sodium/glucose co-transporters 1/2 mRNA and protein expressions. U-73122 pre-treatment alleviated the glucose-induced increase in TAG content, BODIPY 493/503 fluorescence intensity, lipogenic enzymes (glucose 6-phospate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), malic enzyme and fatty acid synthase (FAS)) activity and the mRNA expressions of lipogenic genes and related transcription factors (6pgd, g6pd, fas, acca, srebp1 and carbohydrate response element-binding protein (chrebp)) in intestinal epithelial cells of yellow catfish. Further research found that U-73122 pre-incubation mitigated the glucose-induced increase in the ChREBP protein expression and the acetylation level of ChREBP in HEK293T cells. Taken together, these data demonstrated that the PLC played a major role in the glucose-induced changes of glucose transport and lipid metabolism and provide a new perspective for revealing the molecular mechanism of glucose-induced changes of intestinal glucose absorption, lipid deposition and metabolism.
Narrowband microwave generation with tuneable frequency is demonstrated by illuminating a photoconductive semiconductor switch (PCSS) with a burst-mode fibre laser. The whole system is composed of a high-power linearly polarized burst-mode pulsed fibre laser and a linear-state PCSS. To obtain a high-performance microwave signal, a desired envelope of burst is necessary and a pulse pre-compensation technique is adopted to avoid envelope distortion induced by the gain-saturation effect. Resulting from the technique, homogenous peak power distribution in each burst is ensured. The maximum energy of the laser burst pulse reaches 200 μJ with a burst duration of 100 ns at the average power of 10 W, corresponding to a peak power of 4 kW. When the PCSS is illuminated by the burst-mode fibre laser, narrowband microwave generation with tuneable frequency (0.80–1.12 GHz) is obtained with a power up to 300 W. To the best of the authors’ knowledge, it is the first demonstration of frequency-tuneable narrowband microwave generation based on a fibre laser. The high-power burst-mode fibre laser reported here has great potential for generating high-power arbitrary microwave signals for a great deal of applicable demands such as smart adaptive radar and intelligent high-power microwave systems.
Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design.
This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934).
Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups.
The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine.
The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.
Dysregulation in hepatic lipid synthesis by excess dietary carbohydrate intake is often relevant with the occurrence of fatty liver; therefore, the thorough understanding of the regulation of lipid deposition and metabolism seems crucial to search for potential regulatory targets. In the present study, we examined TAG accumulation, lipid metabolism-related gene expression, the enzyme activities of lipogenesis-related enzymes, the protein levels of transcription factors or genes involving lipogenesis in the livers of yellow catfish fed five dietary carbohydrate sources, such as glucose, maize starch, sucrose, potato starch and dextrin, respectively. Generally speaking, compared with other carbohydrate sources, dietary glucose promoted TAG accumulation, up-regulated lipogenic enzyme activities and gene expressions, and down-regulated mRNA expression of genes involved in lipolysis and small ubiquitin-related modifier (SUMO) modification pathways. Further studies found that sterol regulatory element binding protein 1 (SREBP1), a key transcriptional factor relevant to lipogenic regulation, was modified by SUMO1. Mutational analyses found two important sites for SUMOylation modification (K254R and K264R) in SREBP1. Mutant SREBP lacking lysine 264 up-regulated the transactivation capacity on an SREBP-responsive promoter. Glucose reduced the SUMOylation level of SREBP1 and promoted the protein expression of SREBP1 and its target gene stearoyl-CoA desaturase 1 (SCD1), indicating that SUMOylation of SREBP1 mediated glucose-induced hepatic lipid metabolism. Our study elucidated the molecular mechanism of dietary glucose increasing hepatic lipid deposition and found that the SREBP-dependent transactivation was regulated by SUMO1 modification, which served as a new target for the transcriptional programmes governing lipid metabolism.
The Arsenic (+3 oxidation state) methyltransferase (AS3MT) gene has been identified as a top risk gene for schizophrenia in several large-scale genome-wide association studies. A variable number tandem repeat (VNTR) of this gene is the most significant expression quantitative trait locus, but its role in brain activity in vivo is still unknown.
We first performed a functional magnetic resonance imaging (fMRI) scan of 101 healthy subjects during a memory span task, trained all subjects on an adaptive memory span task for 1 month, and finally performed another fMRI scan after the training. After excluding subjects with excessive head movements for one or more scanning sessions, data from 93 subjects were included in the final analyses.
The VNTR was significantly associated with both baseline brain activation and training-induced changes in multiple regions including the prefrontal cortex and the anterior and posterior cingulate cortex. Additionally, it was associated with baseline brain activation in the striatum and the parietal cortex. All these results were corrected based on the family-wise error rate method across the whole brain at the peak level.
This study sheds light on the role of AS3MT gene variants in neural plasticity related to memory span training.
The microbiota–gut–brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients.
We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD.
The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890.
The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.
Disturbances in lipid metabolism are at the core of several health issues facing modern society, including fatty liver and obesity. The sterol regulatory element-binding protein 1 (SREBP-1) is one important transcription factor regulating lipid metabolism, but the relevant mechanism still remains unknown. The present study determined the transcriptional regulation of SREBP-1 and its target genes (including acetyl-CoA carboxylase α (accα), fatty acid synthase (fas) and stearoyl-CoA desaturase 1 (scd1)) in a freshwater teleost, grass carp Ctenopharyngodon idella. We cloned and characterised the 1988 bp, 2043 bp, 1632 bp and 1889 bp sequences of srebp-1, accα, scd1 and fas promoters, respectively. A cluster of putative binding sites of transcription factors, such as specific protein, yin yang 1, nuclear factor Y, sterol response elements (SRE) and enhancer box (E-box) element, were predicted on their promoter regions. Overexpression of nSREBP-1 reduced srebp-1 promoter activity, increased scd1 and fas promoter activity but did not influence accα promoter activity. The site-mutation and electrophoretic mobility shift assay analysis indicated that srebp-1, fas and scd1 promoters, but not accα promoter, possessed SRE. In Ctenopharyngodon idella kidney (CIK) cells of grass carp, nSREBP-1 overexpression significantly reduced srebp-1 mRNA expression and up-regulated miR-29 mRNA expression. The 3′UTR of srebp-1 possessed the potential miR-29 binding site and miR-29 up-regulated the luciferase activity of srebp-1 3′UTR and srebp-1 mRNA expression, implying a self-activating loop of SREBP-1 and miR-29 in grass carp. Based on the above-mentioned results, we found two novel transcriptional mechanisms for SREBP-1 in grass carp: (1) the auto-regulation sited on the SREBP-1 promoter regions was suppressive and (2) there was a self-activating loop of SREBP-1 and miR-29.