Overexpression of forebrain PTP1B leads to synaptic and cognitive impairments in obesity.

Obesity has reached pandemic proportions and is a risk factor for neurodegenerative diseases, including Alzheimer's disease. Chronic inflammation is common in obese patients, but the mechanism between inflammation and cognitive impairment in obesity remains unclear. Accumulative evidence shows that protein-tyrosine phosphatase 1B (PTP1B), a neuroinflammatory and negative synaptic regulator, is involved in the pathogenesis of neurodegenerative processes. We investigated the causal role of PTP1B in obesity-induced cognitive impairment and the beneficial effect of PTP1B inhibitors in counteracting impairments of cognition, neural morphology, and signaling. We showed that obese individuals had negative relationship between serum PTP1B levels and cognitive function. Furthermore, the PTP1B level in the forebrain increased in patients with neurodegenerative diseases and obese cognitive impairment mice with the expansion of white matter, neuroinflammation and brain atrophy. PTP1B globally or forebrain-specific knockout mice on an obesogenic high-fat diet showed enhanced cognition and improved synaptic ultrastructure and proteins in the forebrain. Specifically, deleting PTP1B in leptin receptor-expressing cells improved leptin synaptic signaling and increased BDNF expression in the forebrain of obese mice. Importantly, we found that various PTP1B allosteric inhibitors (e.g., MSI-1436, well-tolerated in Phase 1 and 1b clinical trials for obesity and type II diabetes) prevented these alterations, including improving cognition, neurite outgrowth, leptin synaptic signaling and BDNF in both obese cognitive impairment mice and a neural cell model of PTP1B overexpression. These findings suggest that increased forebrain PTP1B is associated with cognitive decline in obesity, whereas inhibition of PTP1B could be a promising strategy for preventing neurodegeneration induced by obesity.

Shear-wave elastography in renal stiffness in children with hematuria and/or proteinuria.

BACKGROUND: We sought to evaluate renal stiffness in children with hematuria and/or proteinuria using shear wave elastography (SWE) and to investigate the clinical value of renal stiffness in children with hematuria and/or proteinuria. METHODS: According to the results of urinary occult blood and urinary protein tests, 349 pediatric patients were categorized into one of four groups: pure hematuria (HU), pure proteinuria (PU), concomitant hematuria and proteinuria (HUPU), or control (non-HUPU). Patient demographic data, laboratory test results, and renal ultrasound data were collected. RESULTS: There were significant differences in cortical/medullary elasticity among the four groups (the most sensitive cutoff value between HU and PU was 1.72) (P < 0.05). We found that hematuria and proteinuria interacted with renal cortical elasticity (P < 0.05) but that hematuria and proteinuria did not interact with renal medullary elasticity or cortical/medullary elasticity (P > 0.05). Renal elasticity values correlated with sex, age, body surface area, body mass index, qualitative urinary protein, urine N-acetyl-ß-D-glucosaminidase, 24-hour urinary protein quantity, renal volume, and renal cortical thickness (P < 0.05). CONCLUSIONS: SWE can be used to detect changes in renal stiffness in children with hematuria and/or proteinuria. SWE is beneficial for the early detection of glomerular disease in children with abnormal urine test results. IMPACT: This study evaluated the utility of shear wave elastography for the assessment of renal elasticity in pediatric patients presenting with hematuria and/or proteinuria. Children with pure proteinuria had significantly higher renal cortical/medullary elasticity values than those with pure hematuria. An interaction effect between hematuria and proteinuria on renal cortical stiffness was observed. Shear wave elastography can be used as a tool to assess early renal injury in children with urinalysis abnormalities.

Vitamin D: A potent regulator of dopaminergic neuron differentiation and function.

Vitamin D has been identified as a key factor in dopaminergic neurogenesis and differentiation. Consequently, developmental vitamin D (DVD) deficiency has been linked to disorders of abnormal dopamine signalling with a neurodevelopmental basis such as schizophrenia. Here we provide further evidence of vitamin D's role as a mediator of dopaminergic development by showing that it increases neurite outgrowth, neurite branching, presynaptic protein re-distribution, dopamine production and functional release in various in vitro models of developing dopaminergic cells including SH-SY5Y cells, primary mesencephalic cultures and mesencephalic/striatal explant co-cultures. This study continues to establish vitamin D as an important differentiation agent for developing dopamine neurons, and now for the first time shows chronic exposure to the active vitamin D hormone increases the capacity of developing neurons to release dopamine. This study also has implications for understanding mechanisms behind the link between DVD deficiency and schizophrenia.

Theoretical Study on the Formation and Decomposition Mechanisms of Coelenterazine Dioxetanone.

Bioluminescence has been drawing broad attention due to its high signal-to-noise ratio and high bioluminescence quantum yields, which has been widely applied in the fields of biomedicine, bioanalysis, and so on. Among numerous bioluminescent substrates, coelenterazine is famous for its wide distribution. However, the oxygenation reaction mechanism of coelenterazine is far from being completely understood. In this paper, the formation and decomposition mechanisms of coelenterazine dioxetanone were investigated via density functional theory (DFT) and time-dependent (TD) DFT approaches. The results showed that the oxygenation reaction first occurred along the triplet-state potential energy surface (PES), after the intersystem crossing (ISC), second jumped to the diradical-state PES, and ultimately formed coelenterazine dioxetanone. For the decomposition mechanism of dioxetanone, the computational results showed that the chemiexcitation of neutral dioxetanone was more efficient than that of other dioxetanone species. Moreover, the diradical properties and the degree of ionic character are modified by the counter ions.

Vitamin D and schizophrenia: 20 years on.

Many epidemiological studies have highlighted the link between vitamin D deficiency and schizophrenia. In particular, two prominent studies report an association between neonatal vitamin D deficiency and an increased risk of schizophrenia. In parallel, much has been learnt about the role of vitamin D in the developing central nervous system over the last two decades. Studies in rodent models of developmental vitamin D (DVD)-deficiency describe how brain development is altered leading to a range of neurobiological and behavioral phenotypes of interest to schizophrenia. While glutamate and gamma aminobutyric acid (GABA) systems have been little investigated in these models, alterations in developing dopamine systems are frequently reported. There have been far more studies reporting patients with schizophrenia have an increased risk of vitamin D deficiency compared to well controls. Here we have conducted a systematic review and meta-analysis that basically confirms this association and extends this to first-episode psychosis. However, patients with schizophrenia also have poorer general health, poorer diets, are frequently less active and also have an increased risk of other medical conditions, all factors which reduce circulating vitamin D levels. Therefore, we would urge caution in any causal interpretation of this association. We also summarize the inconsistent results from existing vitamin D supplementation trials in patients with schizophrenia. In respect to animal models of adult vitamin D deficiency, such exposures produce subtle neurochemical alterations and effects on cognition but do not appear to produce behavioral phenotypes of relevance to schizophrenia. We conclude, the hypothesis that vitamin D deficiency during early life may increase the risk of schizophrenia remains plausible and warrants ongoing research.

Three LHPP gene-targeting co-expressed microRNAs (microRNA-765, microRNA-21, and microRNA-144) promote proliferation, epithelial-mesenchymal transition, invasion, and are independent prognostic biomarkers in renal cell carcinomas patients.

BACKGROUND: Renal cell carcinoma (RCC) is one of the highly malignant tumors in the world. Global Cancer Statistics 2020 estimated that there were 179,368 deaths from kidney tumors. Therefore, exploring the prognostic biomarkers of RCC is of great significance for RCC patients. This study aims to explore the potential mechanism and prognostic value of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) gene-targeting co-expression microRNAs in RCC patients. METHODS: A total of 60 RCC patients were included. Quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry were used for LHPP, microRNA-765, microRNA-21, and microRNA-144 levels evaluation. Cell Counting Kit-8 assay, dual-luciferase reporter gene assay, invasion assay, and RNA fluorescence in situ hybridization were used for functional analyses. RESULTS: Compared with adjacent tissues, LHPP levels in cancer tissues were significantly increased (p < .001). Herein, we confirmed that microRNA-765, microRNA-21, and microRNA-144 were direct biological targets of LHPP. MicroRNA-765 (r = -0.570, p < 0.001), microRNA-21 (r = -0.495, p < .001), and microRNA-144 (r = -0.463, p < .001) expression levels were negatively correlated with LHPP expression levels. The high expression levels of microRNA-765, microRNA-21, and microRNA-144 in RCC tissues were associated with poor differentiation, recurrence, and poor prognosis (p < .05). In vitro, microRNA-765, microRNA-21, and microRNA-144 act as oncogenes to promote proliferation, invasion, and epithelial-mesenchymal transition (EMT) through targeting LHPP. CONCLUSIONS: MicroRNA-765, microRNA-21, and microRNA-144 are independent risk biomarkers for RCC patients. Inhibiting the expression levels of microRNA-765, microRNA-21, and microRNA-144 can reduce the proliferation, EMT, and invasion of RCC cells. Therefore, the above three microRNAs are expected to become molecular biomarkers for RCC therapy.

Developmental Inhibition of Long Intergenic Non-Coding RNA, HOTAIRM1, Impairs Dopamine Neuron Differentiation and Maturation.

The dopaminergic (DA) system is important for a range of brain functions and subcortical DA development precedes many cortical maturational processes. The dysfunction of DA systems has been associated with neuropsychiatric disorders such as schizophrenia, depression, and addiction. DA neuron cell fate is controlled by a complex web of transcriptional factors that dictate DA neuron specification, differentiation, and maturation. A growing body of evidence suggests that these transcriptional factors are under the regulation of newly discovered non-coding RNAs. However, with regard to DA neuron development, little is known of the roles of non-coding RNAs. The long non-coding RNA (lncRNA) HOX-antisense intergenic RNA myeloid 1 (HOTAIRM1) is present in adult DA neurons, suggesting it may have a modulatory role in DA systems. Moreover, HOTAIRM1 is involved in the neuronal differentiation in human stem cells suggesting it may also play a role in early DA neuron development. To determine its role in early DA neuron development, we knocked down HOTAIRM1 using RNAi in vitro in a human neuroblastoma cell line, and in vivo in mouse DA progenitors using a novel in utero electroporation technique. HOTAIRM1 inhibition decreased the expression of a range of key DA neuron specification factors and impaired DA neuron differentiation and maturation. These results provide evidence of a functional role for HOTAIRM1 in DA neuron development and differentiation. Understanding of the role of lncRNAs in the development of DA systems may have broader implications for brain development and neurodevelopmental disorders such as schizophrenia.

FOXD3 inhibits cell proliferation, migration, and invasion in nasopharyngeal carcinoma through regulation of the PI3K-Akt pathway.

FOXD3 has been found previously to positively regulate miR-26b, a tumor inhibitor of nasopharyngeal carcinoma (NPC). However, FOXD3's precise function and associated mechanism of action in NPC have not yet been investigated. In this study, the expression of FOXD3 mRNA and protein was evaluated using RT-qPCR, western blotting, and immunohistochemistry. Protein levels involved in the phosphoinositide 3-kinase - protein kinase B (PI3K-Akt) pathway were assessed by western blot, and cell proliferation was determined by MTT and colony forming assays. Additionally, cell apoptosis was assessed by flow cytometric assay. Finally, the migration and invasion capabilities of the NPC cells were determined using wound healing and Transwell assays. We found that FOXD3 levels were relatively low in NPC tissue and cells, while an increase caused the inhibition of the PI3K-Akt pathway. Functional experiments found that overexpression of FOXD3 suppressed cell proliferation, migration, and invasion and enhanced cell apoptosis in NPC C6661 cells. IGF-1, an activator of the PI3K-Akt pathway, reversed the inhibitory effect of FOXD3. Furthermore, we found upregulation of the PI3K-Akt pathway and upregulation of the inhibitory effects of FOXD3 on C6661 cellular activities. In conclusion, FOXD3 negatively affected the PI3K-Akt pathway to restrain the processes involved in C6661 cell pathology. These findings further exposed the function and downstream axis of FOXD3 in NPC and displayed a promising new target for NPC therapy.

Micropapillary pattern of stage IIIA-N2 lung adenocarcinoma is a prognostic factor after adjuvant chemoradiotherapy.

Aim: This study aims to investigate the significance of a micropapillary pattern in stage IIIA-N2 lung adenocarcinoma after adjuvant chemoradiotherapy. Patients & methods: A total of 257 patients with stage IIIA-N2 lung adenocarcinoma were enrolled in this study. Patients were classified into three groups based on the proportion of micropapillary components: micropapillary negative, micropapillary minor component and micropapillary predominant component. Results: The micropapillary predominant group had the shortest median disease-free survival and overall survival times compared with the micropapillary minor component and micropapillary negative groups (median overall survival time: 54 months vs 64 months vs not reached; p = 0.004). Furthermore, the micropapillary pattern was an independent prognostic factor for disease-free survival and overall survival (p < 0.05). Conclusion: The micropapillary pattern of IIIA-N2 lung adenocarcinoma is related to worse prognosis.

Combined Use of Three Machine Learning Modeling Methods to Develop a Ten-Gene Signature for the Diagnosis of Ventilator-Associated Pneumonia.

BACKGROUND This study aimed to use three modeling methods, logistic regression analysis, random forest analysis, and fully-connected neural network analysis, to develop a diagnostic gene signature for the diagnosis of ventilator-associated pneumonia (VAP). MATERIAL AND METHODS GSE30385 from the Gene Expression Omnibus (GEO) database identified differentially expressed genes (DEGs) associated with patients with VAP. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment identified the molecular functions of the DEGs. The least absolute shrinkage and selection operator (LASSO) regression analysis algorithm was used to select key genes. Three modeling methods, including logistic regression analysis, random forest analysis, and fully-connected neural network analysis, also known as also known as the feed-forward multi-layer perceptron (MLP), were used to identify the diagnostic gene signature for patients with VAP. RESULTS Sixty-six DEGs were identified for patients who had VAP (VAP+) and who did not have VAP (VAP-). Ten essential or feature genes were identified. Upregulated genes included matrix metallopeptidase 8 (MMP8), arginase 1 (ARG1), haptoglobin (HP), interleukin 18 receptor 1 (IL18R1), and NLR family apoptosis inhibitory protein (NAIP). Down-regulated genes included complement factor D (CFD), pleckstrin homology-like domain family A member 2 (PHLDA2), plasminogen activator, urokinase (PLAU), laminin subunit beta 3 (LAMB3), and dual-specificity phosphatase 2 (DUSP2). Logistic regression, random forest, and MLP analysis showed receiver operating characteristic (ROC) curve area under the curve (AUC) values of 0.85, 0.86, and 0.87, respectively. CONCLUSIONS Logistic regression analysis, random forest analysis, and MLP analysis identified a ten-gene signature for the diagnosis of VAP.

Vitamin D regulation of GDNF/Ret signaling in dopaminergic neurons.

1,25(OH)2D3 (vitamin D) appears essential for the normal development of dopaminergic neurons. Vitamin D affects dopamine synthesis and metabolism as well as expression of glial cell line-derived neurotrophic factor (GDNF), which is crucial for the survival of dopaminergic neurons. We investigated the role of vitamin D on GDNF and its receptors protooncogene tyrosine-protein kinase receptor Ret (C-Ret) and GDNF family receptor alpha 1 (GFRα1) signaling. To this end, we used a developmental vitamin D-deficient rat model and SH-SY5Y cells transfected with vitamin D receptor (VDR). The absence of vitamin D ligand in gestation reduces C-Ret expression, but not GDNF and GFRα1, in embryo forebrains. Overexpression of VDR in SH-SY5Y in the absence of ligand (mimicking in vivo developmental vitamin D deficiency) also suppressed C-Ret mRNA levels. In the presence of vitamin D, C-Ret mRNA and protein expression were increased. The chromatin immunoprecipitation results suggested that C-Ret is directly regulated by vitamin D via VDR. GDNF was also increased by vitamin D in these cells. Our small interfering RNA studies showed that knocking down VDR leads to an increase in C-Ret in the absence of ligand. Finally, we confirmed the inverse relationship between GFRα1 and C-Ret, as knocking down C-Ret led to increases in GFRα1 expression. These data extend our knowledge of the diverse and important roles played by vitamin D in dopamine physiology.-Pertile, R. A. N., Cui, X., Hammond, L., Eyles, D. W. Vitamin D regulation of GDNF/Ret signaling in dopaminergic neurons.

MagT1 is essential for Drosophila development through the shaping of Wingless and Decapentaplegic signaling pathways.

Magnesium transporter subtype 1 (MagT1) is a magnesium membrane transporter with channel like properties. We have previously identified MagT1 (CG7830) in Drosophila genome and characterized its protein product by electrophysiological means. Here, we report the generation of fly MagT1 mutants and show that MagT1 is essential for early embryonic development. In wings and primordial wings, by clonal analysis and RNAi knock down of MagT1, we have found that loss of MagT1 results in enhanced/ectopic Wingless (Wg, a fly Wnt) signaling and disrupted Decapentaplegic (Dpp) signaling, indicating the crucial role of MagT1 for fly development at later stages. Finally, we demonstrate directly that magnesium transportations are proportional with the MagT1 expressional levels in Drosophila S2  cells. Taken together, these findings may suggest that MagT1 is a major magnesium transporter/channel profoundly involved in fly development by affecting developmental signaling pathways, such as Wg and Dpp signaling.

Water quality criteria derivation and ecological risk assessment for triphenyltin in China.

Triphenyltin (TPT) is one of the most toxic chemicals artificially discharged into aquatic environment with human activities. Due to its intensive use in antifouling paints and adverse effects on non-target species, TPT has aroused wide concern in both saltwater and freshwater environment. Nevertheless, the water quality criteria (WQC) are not available in China, which impedes the risk assessment for this emerging pollutant. This study aims to establish the WQC of TPT for both freshwater and saltwater ecosystems. With the derived WQC, a four-level tiered ecological risk assessment (ERA) approach was employed to assess the ecological risks of this emerging pollutant in Chinese waters. Through the species sensitivity distribution (SSD) methodology, the freshwater criterion maximum concentration (CMC) and criterion continuous concentration (CCC) were derived as 396 ng Sn L-1 and 5.60 ng Sn L-1, respectively, whereas the saltwater CMC and CCC were 66.5 ng Sn L-1 and 4.11 ng Sn L-1, respectively. The ecological risk assessment for TPT demonstrated that the acute risk was negligible whereas the chronic risk was significant with HQ (Hazard Quotient) values of up to 5.669 and 57.1% of coastal waters in China facing clear risk. TPT contamination in coastal environment, therefore, warrants further concern.

Meta-analysis of the hazards of microplastics in freshwaters using species sensitivity distributions.

The environmental hazards of microplastics have raised concerns about their potential ecological risks. However, our understanding of the true risks may be limited because most laboratory studies used pristine microplastics. Here, we analyzed the available literature about ecotoxicological effects of microplastics, including weathered microplastics in particular, on freshwater biota and performed probabilistic species sensitivity distributions. The predicted no-effect concentrations for pristine microplastics were lower than those for weathered microplastics, both in mass concentration (6.1 and 4.8 × 102 µg/L) and number concentration (2.6 × 104 and 2.0 × 106 part/m3). In addition, the toxicological studies on microplastics contains often inconsistent and inconclusive information due to the complexity of the microplastics and the employed exposure conditions. The available data for Daphnia magna and Danio rerio was analyzed in detail to understand the effects of microplastic size, shape and polymer type on their ecotoxicity. Microplastic size was the biggest driving factor, followed by shape and polymer type. There was a tendency for increasing toxicity with smaller size, however, a high variability of effect data was observed for small microplastics. This study provided further insights into the effect thresholds for ecological risk assessment of microplastics and the effects of microplastic characteristics on toxicity.

Exo â ¢-assisted amplification signal strategy synergized with Au@Pt NFs/CoSe2 for sensitive detection of enrofloxacin.

Overuse of enrofloxacin (ENR) has posed a potential threat to ecosystems and public health, so it is critical to sensitive and accurate determination of ENR residues. In this work, a novel ultra-sensitive and specific electrochemical aptasensor was fabricated based on the cobalt diselenide loaded gold and platinum nanoflowers (Au@Pt NFs/ CoSe2) and Exonuclease III (Exo III)-assisted cycle amplification strategy for the detection of ENR. Au@Pt NFs/ CoSe2 nanosheets as the substrate material, with large surface area, accelerate electron transfer and attach more DNA probes on the electrode substrate, have effectively enhanced the electrochemical performance of the electrode. With the existence of Enrofloxacin (ENR), the aptamer recognizes and binds to ENR, thus the signal probe cDNA was released and immobilized onto the electrode surface to hybridized with methylene blue (MB) labelled DNA (MB-DNA), thereby triggering the Exo III-assisted cycle for further signal amplification. As expected, the prepared aptasensor demonstrated excellent sensitivity and selectivity, with a wide linear range from 5.0 × 10-6 ng/mL to 1.0 × 10-2 ng/mL for ENR, a low detection limit of 1.59 × 10-6 ng/mL. Consequently, this strategy provided a promising avenue for ultrasensitive and accurate detection of ENR in milk samples.

Olanzapine attenuates 5-HT2cR and GHSR1a interaction to increase orexigenic hypothalamic NPY: Implications for neuronal molecular mechanism of metabolic side effects of antipsychotics.

The main cause of second-generation antipsychotic (SGA)-induced obesity is considered due to the antagonism of serotonin 2c receptors (5-HT2cR) and activation of ghrelin receptor type 1a (GHSR1a) signalling. It is reported that 5-HT2cR interacted with GHSR1a, however it is unknown whether one of the SGA olanzapine alters the 5-HT2cR/GHSR1a interaction, affecting orexigenic neuropeptide signalling in the hypothalamus. We found that olanzapine treatment increased average energy intake and body weight gain in mice; olanzapine treatment also increased orexigenic neuropeptide (NPY) and GHSR1a signaling molecules, pAMPK, UCP2, FOXO1 and pCREB levels in the hypothalamus. By using confocal fluorescence resonance energy transfer (FRET) technology, we found that 5-HT2cR interacted/dimerised with the GHSR1a in the hypothalamic neurons. As 5-HT2cR antagonist, both olanzapine and S242084 decreased the interaction between 5-HT2cR and GHSR1a and activated GHSR1a signaling. The 5-HT2cR agonist lorcaserin counteracted olanzapine-induced attenuation of interaction between 5-HT2cR and GHSR1a and inhibited activation of GHSR1a signalling and NPY production. These findings suggest that 5-HT2cR antagonistic effect of olanzapine in inhibition of the interaction of 5-HT2cR and GHSR1a, activation GHSR1a downstream signaling and increasing hypothalamic NPY, which may be the important neuronal molecular mechanism underlying olanzapine-induced obesity and target for prevention metabolic side effects of antipsychotic management in psychiatric disorders.

Increasing dopamine synthesis in nigrostriatal circuits increases phasic dopamine release and alters dorsal striatal connectivity: implications for schizophrenia.

One of the most robust neurochemical abnormalities reported in patients with schizophrenia is an increase in dopamine (DA) synthesis and release, restricted to the dorsal striatum (DS). This hyper functionality is strongly associated with psychotic symptoms and progresses in those who later transition to schizophrenia. To understand the implications of this progressive neurobiology on brain function, we have developed a model in rats which we refer to as EDiPs (Enhanced Dopamine in Prodromal schizophrenia). The EDiPs model features a virally mediated increase in dorsal striatal (DS) DA synthesis capacity across puberty and into adulthood. This protocol leads to progressive changes in behaviour and neurochemistry. Our aim in this study was to explore if increased DA synthesis capacity alters the physiology of DA release and DS connectivity. Using fast scan cyclic voltammetry to assess DA release we show that evoked/phasic DA release is increased in the DS of EDiPs rats, whereas tonic/background levels of DA remain unaffected. Using quantitative immunohistochemistry methods to quantify DS synaptic architecture we show a presynaptic marker for DA release sites (Bassoon) was elevated within TH axons specifically within the DS, consistent with the increased phasic DA release in this region. Alongside changes in DA systems, we also show increased density of vesicular glutamate transporter 1 (VGluT1) synapses in the EDiPs DS suggesting changes in cortical connectivity. Our data may prove relevant in understanding the long-term implications for DS function in response to the robust and prolonged increases in DA synthesis uptake and release reported in schizophrenia.

Changes in sulfur in soybean rhizosphere soil and the response of microbial flora in a continuous cropping system mediated by Funneliformis mosseae.

Soybean is an S-loving crop, and continuous cropping might cause soil sulfur shortage. The primary objectives of this study are to determine whether Funneliformis mosseae (F. mosseae) can enhance the content of available S in S-deficient soil and thereby improve the sulfur utilization rate in soybean. The experiment used Heinong 48 (HN48), a soybean variety with a vast planting area in Heilongjiang Province, and F. mosseae was inoculated in the soil of soybean that had been continuously cropped for 0 and 3 years. The results of the barium sulfur turbidimetric assay show that the sulfur content in the soil and soybean was reduced by continuous cropping and increased by inoculation with F. mosseae; the results of the macro-genome sequencing technology, show that the diversity and abundance of bacteria in the soil was decreased by continuous cropping and increased by inoculation with F. mosseae. The sulfur-oxidizing bacteria (SOB) activity and sulfur-related gene expression levels were lower in the continuous crop group compared to the control group and higher in the F.mosseae-inoculated group compared to the control group. Continuous cropping reduced the sulfur content and ratio of soybean rhizosphere soil, affecting soil flora activity and thus soybean growth; F. mosseae inoculation increased the sulfur content of soybean root-perimeter soil and plants, increased the diversity and abundance of rhizosphere soil microorganisms, increased the expression of genes for sulfur transport systems, sulfur metabolism, and other metabolic functions related to elemental sulfur, and increased the species abundance and metabolic vigor of most SOB. In summary, continuous cropping inhibits soil sulfur uptake and utilization in soybean while the inoculation with F. mosseae can significantly improve this situation. This study offers a theoretical research foundation for using AMF as a bio-fungal agent to enhance soil sulfur use. It also supports the decrease of chemical fertilizers, their substitution, and the protection of native soil.

Propofol EC50 for inducing loss of consciousness in patients under combined epidural-general anesthesia or general anesthesia alone: a randomized double-blind study.

Background: Combined epidural-general anesthesia (GA + EA) has been recommended as a preferred technique for both thoracic and abdominal surgery. The epidural anesthesia on the general anesthetic (GA) requirements has not been well investigated. Therefore, we conducted the present study to explore the predicted effect-site concentration of propofol (Ceprop) required for achieving the loss of consciousness (LOC) in 50% of patients (EC50) with or without epidural anesthesia. Methods: Sixty patients scheduled for gastrectomy were randomized into the GA + EA group or GA alone group to receive general anesthesia alone. Ropivacaine 0.375% was used for epidural anesthesia to achieve a sensory level of T4 or above prior to the induction of general anesthesia. The EC50 of predicted Ceprop for LOC was determined by the up-down sequential method. The consumption of anesthetics, emergence time from anesthesia, and postoperative outcomes were also recorded and compared. Results: The EC50 of predicted Ceprop for LOC was lower in the GA + EA group than in the GA alone group [2.97 (95% CI: 2.63-3.31) vs. 3.36 (95% CI: 3.19-3.53) µg mL-1, (p = 0.036)]. The consumption of anesthetics was lower in the GA + EA group than in the GA alone group (propofol: 0.11 ± 0.02 vs. 0.13 ± 0.02 mg kg-1 min-1, p = 0.014; remifentanil: 0.08 ± 0.03 vs. 0.14 ± 0.04 µg kg-1 min-1, p < 0.001). The emergence time was shorter in the GA + EA group than in the GA alone group (16.0 vs. 20.5 min, p = 0.013). Conclusion: Concomitant epidural anesthesia reduced by 15% the EC50 of predicted Ceprop for LOC, decreased the consumptions of propofol and remifentanil during maintenance of anesthesia, and fastened recovery from anesthesia. Clinical trial registration: ClinicalTrials.gov, identifier: NCT05124704.

Developmental vitamin D-deficiency produces autism-relevant behaviours and gut-health associated alterations in a rat model.

Developmental vitamin D (DVD)-deficiency is an epidemiologically established risk factor for autism. Emerging studies also highlight the involvement of gut microbiome/gut physiology in autism. The current study aims to examine the effect of DVD-deficiency on a broad range of autism-relevant behavioural phenotypes and gut health. Vitamin D deficient rat dams exhibited altered maternal care, DVD-deficient pups showed increased ultrasonic vocalizations and as adolescents, social behaviour impairments and increased repetitive self-grooming behaviour. There were significant impacts of DVD-deficiency on gut health demonstrated by alterations to the microbiome, decreased villi length and increased ileal propionate levels. Overall, our animal model of this epidemiologically validated risk exposure for autism shows an expanded range of autism-related behavioural phenotypes and now alterations in gut microbiome that correlate with social behavioural deficits raising the possibility that DVD-deficiency induced ASD-like behaviours are due to alterations in gut health.