Two-billion-year-old volcanism on the Moon from Chang'e-5 basalts.

The Moon has a magmatic and thermal history that is distinct from that of the terrestrial planets1. Radioisotope dating of lunar samples suggests that most lunar basaltic magmatism ceased by around 2.9-2.8 billion years ago (Ga)2,3, although younger basalts between 3 Ga and 1 Ga have been suggested by crater-counting chronology, which has large uncertainties owing to the lack of returned samples for calibration4,5. Here we report a precise lead-lead age of 2,030 ± 4 million years ago for basalt clasts returned by the Chang'e-5 mission, and a 238U/204Pb ratio (µ value)6 of about 680 for a source that evolved through two stages of differentiation. This is the youngest crystallization age reported so far for lunar basalts by radiometric dating, extending the duration of lunar volcanism by approximately 800-900 million years. The µ value of the Chang'e-5 basalt mantle source is within the range of low-titanium and high-titanium basalts from Apollo sites (µ value of about 300-1,000), but notably lower than those of potassium, rare-earth elements and phosphorus (KREEP) and high-aluminium basalts7 (µ value of about 2,600-3,700), indicating that the Chang'e-5 basalts were produced by melting of a KREEP-poor source. This age provides a pivotal calibration point for crater-counting chronology in the inner Solar System and provides insight on the volcanic and thermal history of the Moon.

Rapid and Complete Digestion of Refractory Geological Samples Using Ultrafine Powder for Accurate Analyses of Trace Elements.

Complete sample digestion is a prerequisite for acquiring high-quality analytical results for geological samples. Closed-vessel acid digestion (bomb) has typically been used for the total digestion of refractory geological samples. However, the long digestion time (4-5 days) and insoluble fluoride complexes still pose challenges for digesting refractory geological samples using this approach. In this study, an efficient and simplified digestion technique combining ultrafine powders from planetary ball milling with bomb digestion was developed for trace element analysis of refractory geological samples: peridotite and granitoid. The method shows two significant improvements compared with previous approaches. (1) By performing dry planetary ultrafine milling, the initial 200 mesh peridotite (<74 µm) could be reduced to 800 mesh (<20 µm) in 6 min at a ball-to-powder mass ratio of approximately 15 using 3 mm tungsten carbide milling balls. (2) Complete peridotite and granitoid dissolution were achieved in approximately 2 h, 60 times faster than what is achievable using previous methods (2 h vs 120 h). Moreover, ultrafine powders effectively suppressed insoluble fluoride formation during bomb digestion. A suite of peridotite and granitoid reference materials were measured to evaluate the stability of this method. This efficient, simple, and reliable sample digestion method could benefit geological, food, environmental, and other fields requiring solid sample decomposition via wet acid, fusion, combustion, or dry ashing.

Individualized driver amplitude in liver MR elastography: a linear regression study.

BACKGROUND: Current liver magnetic resonance elastography (MRE) scans often require adjustments to driver amplitude to produce acceptable images. This could lead to time wastage and the potential loss of an opportunity to capture a high-quality image. PURPOSE: To construct a linear regression model of individualized driver amplitude to improve liver MRE image quality. MATERIAL AND METHODS: Data from 95 liver MRE scans of 61 participants, including abdominal missing volume ratio (AMVR), breath-holding status, the distance from the passive driver on the skin surface to the liver edge (Dd-l), body mass index (BMI), and lateral deflection of the passive driver with respect to the human sagittal plane (Angle α), were continuously collected. The Spearman correlation analysis and lasso regression were conducted to screen the independent variables. Multiple linear regression equations were developed to determine the optimal amplitude prediction model. RESULTS: The optimal formula for linear regression models: driver amplitude (%) = -16.80 + 78.59 × AMVR - 11.12 × breath-holding (end of expiration = 1, end of inspiration = 0) + 3.16 × Dd-l + 1.94 × BMI + 0.34 × angle α, with the model passing the F test (F = 22.455, P <0.001) and R2 value of 0.558. CONCLUSION: The individualized amplitude prediction model based on AMVR, breath-holding status, Dd-l, BMI, and angle α is a valuable tool in liver MRE examination.

The effects of tourniquet use on blood loss and perioperative complications in total knee arthroplasty.

BACKGROUND: There has been ongoing debate about the use of tourniquets in total knee arthroplasty, and their application is widely studied. A comprehensive understanding of the advantages and disadvantages of tourniquet use during the procedure is crucial for optimizing surgical outcomes. This study aimed to investigate the effectiveness of tourniquet application, with a particular focus on blood loss and perioperative complications, providing valuable insights for clinical practice. METHODS: Fifty patients who underwent total knee arthroplasty were randomized into tourniquet (n = 25) and nontourniquet (n = 25) groups. The same surgeon performed all surgical procedures. The follow-up time was 14 days after surgery. Primary outcomes were hemoglobin level changes, blood loss, operation time, and perioperative plasma D-dimer levels. Secondary outcomes were postoperative complications, including thrombotic and nonthrombotic events. RESULTS: No significant differences were found in drainage, calculated blood loss, total blood loss, postoperative hemoglobin levels, or blood transfusion between the two groups (P > 0.05). No differences in D-dimer levels were observed on postoperative Days 1, 3, and 14 between the two groups, except on postoperative Day 7, when the D-dimer level in the tourniquet group was lower than that in the nontourniquet group (P = 0.03). The incidence of local complications (thigh bruising, blisters, pain, fat liquefaction, and superficial infections) in the tourniquet group was significantly higher than that in the nontourniquet group (P = 0.03), but no significant differences were found in thromboembolic and nonthromboembolic events or overall complications (P > 0.05). CONCLUSION: We conclude that tourniquet use does not reduce the length of surgery or blood loss but does increase local complications in total knee arthroplasty.

Effects of neuraxial or general anaesthesia on postoperative adverse events in oldest-old patients (aged 90 years and older) with intertrochanteric fractures: a retrospective study.

BACKGROUND: To retrospectively analyse postoperative adverse events in oldest-old patients (aged 90 years and older) with intertrochanteric fractures treated under various anaesthetic techniques. METHODS: A total of 153 consecutive patients participated in this study, of which 127 patients who underwent surgery with neuraxial anaesthesia or general anaesthesia for intertrochanteric fractures between October 2019 and October 2022 were eligible and evaluated. They were divided into the neuraxial anaesthesia and general anaesthesia groups. The demographic characteristics and postoperative adverse events were compared between the two groups. RESULTS: A total of 13 patients (10.24%), including 6 in the neuraxial anaesthesia group (8.22%) and 7 in the general anaesthesia group (12.96%), died within 30 days after surgery. No significant differences between the two groups were observed. Postoperative delirium occurred in 40 patients (31.49%), including 17 (23.29%) in the neuraxial anaesthesia group and 23 (42.59%) in the general anaesthesia group; there was a significant difference between the two groups [P = 0.02, odds ratio (OR) = 0.41]. The other postoperative adverse events, including heart failure, acute stroke, acute myocardial infarction, pulmonary disease, anaemia, deep vein thrombosis, hypoproteinaemia, and electrolyte disorders, were not significantly different between the two groups. CONCLUSION: Our data suggest that different anaesthesia methods do not affect the incidence of adverse events, such as death within 30 days after surgery in oldest-old patients with intertrochanteric fractures. However, more patients developed delirium after surgery in the general anaesthesia group (23, 42.59%) than in the neuraxial anaesthesia group (17, 23.29%); this may indicate that spinal anaesthesia reduces the incidence of postoperative delirium (P = 0.02, OR = 0.41). TRIAL REGISTRATION: Retrospectively registered.

[Effects of mycorrhizal planting on small molecular chemical components of Dendrobium officinale].

This study aimed to provide a scientific basis for the application of the mycorrhizal planting technology of Dendrobium officinale by investigating the effects of mycorrhizal planting on the fingerprints of D. officinale and the content of six chemical components. Seventeen samples of D. officinale under mycorrhizal and conventional planting were collected from four regions, such as Jinhua of Zhejiang. The HPLC fingerprints were established to evaluate the similarity of the samples. The content of six chemical components of the samples was determined by HPLC. There were 15 common peaks in the fingerprints, and five of them were identified by marker compounds, which were naringenin, 4,4'-dihydroxy-3,5-dimethoxybibenzyl, 3,4'-dihydroxy-5-methoxybibenzyl, 3',4-dihydroxy-3,5'-dimethoxybibenzyl(gigantol), and 3,4-dihydroxy-4',5-dimethoxybibenzyl(DDB-2). The similarities of the fingerprints of mycorrhizal and conventional planting samples and the control fingerprint were in the ranges of 0.733-0.936 and 0.834-0.942, respectively. The influences of mycorrhizal planting on fingerprints were related to planting regions, the germplasm of D. officianle, and the amount of fungal agent. The content of six chemical components in the samples varied greatly, and the content of DDB-2 was the highest, ranging from 69.83 to 488.47 µg·g~(-1). The mycorrhizal planting samples from Chongming of Shanghai and Taizhou of Jiangsu showed an increase in the content of 5-6 components, while samples from Zhangzhou of Fujian and Jinhua of Zhejiang showed an increase in the content of 1-2 components. The results showed that mycorrhizal planting technology did not change the chemical profile of small molecular chemical components of D. officinale, but affected the content of chemical components such as bibenzyls, which has a good application prospect.

[Effect of traditional Chinese medicine in attenuating chronic kidney disease and its complications by regulating gut microbiota-derived metabolite trimethylamine N-oxide: a review].

Trimethylamine N-oxide(TMAO), a metabolite of gut microbiota, is closely associated with chronic kidney disease(CKD). It can aggravate the kidney injury and promote the occurrence of complications of CKD mainly by inducing renal fibroblast activation, vascular endothelial inflammation, macrophage foaming, platelet hyperreactivity, and inhibition of reverse cholesterol transport. Thus it is of great significance for clinical treatment of CKD to regulate circulating TMAO and alleviate its induced body damage. Currently, therapeutic strategies for TMAO regulation include dietary structure adjustment, lifestyle intervention, intestinal microflora regulation, and inhibition of intestinal trimethylamine synthesis and liver trimethylamine oxidation. Chinese medicinal herbs have the clinical advantage of multi-component and multi-target effects, and application of traditional Chinese medicine(TCM) to synergistically regulating TMAO and improving CKD via multiple pathways has broad prospects. This study systematically reviewed the clinical relevance and mechanism of TMAO in aggravating CKD renal function deterioration and complication progression. In addition, the effect and mechanism of TCM in improving TMAO-induced kidney injury, cardiovascular disease, hyperlipidemia, thrombosis and osteoporosis were summarized. The results provided a theoretical basis for TCM in attenuating gut microbiota-derived metabolite TMAO and improving CKD, as well as a basis and direction for in-depth clinical development and mechanism research in the future.

Potential Specificity Between Mycorrhizal Fungi Isolated from Widespread Dendrobium spp. and Rare D. huoshanense Seeds.

In nature, orchid seed germination and seedling development depend on compatible mycorrhizal fungi. Mycorrhizal generalist and specificity affect the orchid distribution and rarity. Here, we investigated the specificity toward fungi in the rare D. huoshanense by mycorrhizal fungal isolation and symbiotic germination in vitro. Twenty mycorrhizal fungal strains were isolated from the roots of adult Dendrobium spp. (six and 12 strains from rare D. huoshanense and widespread D. officinale, respectively, and two strains from D. nobile and D. moniliforme, respectively) and 13 strains belong to Tulasnellaceae and seven strains belong to Serendipitaceae. Germination trials in vitro revealed that all 20 tested fungal strains can stimulate seed germination of D. huoshanense, but only nine strains (~ 50%) can support it up to the seedling stage. This finding indicates that generalistic fungi are important for early germination, but only a few can maintain a symbiosis with host in seedling stage. Thus, a shift of the microbial community from seedling to mature stage probably narrows the D. huoshanense distribution range. In addition, to further understand the relationship between the fungal capability to promote seed germination and fungal enzyme activity, we screened the laccase and pectase activity. The results showed that the two enzymes activities of fungi cannot be directly correlated with their germination-promoting activities. Understanding the host specificity degree toward fungi can help to better interpret the limited geographic distribution of D. huoshanense and provides opportunities for in situ and ex situ conservation and reintroduction programs.

Icarisid II rescues cognitive dysfunction via activation of Wnt/ß-catenin signaling pathway promoting hippocampal neurogenesis in APP/PS1 transgenic mice.

Restoring the compromised neurogenesis has been served as a potential strategy to rescue cognitive dysfunction of Alzheimer's disease (AD). In this study, we explored whether icarisid II (ICS II), a natural product possessing powerful neuroprotection, could recover the neurogenesis dysfunction of APP/PS1 mice, and investigated its underlying mechanisms. Our results showed that oral administration of ICS II could alleviate cognitive injuries of APP/PS1 mice, promote hippocampal neurogenesis, as well as stimulate Wnt/ß-catenin signal pathway confirmed by upregulated Wnt-3a, phosphorylated glycogen synthase kinase-3ß (p-GSK-3ß), and ß-catenin. ICS II also depressed mitochondrial fission evidenced by upregulated Mitofusin 1 (Mfn 1) and Mitofusin 2 (Mfn 2), and downregulated mitochondrial fission 1 protein (Fis 1), mitochondrial fission factor (Mff), and phosphorylated dynamin-related protein 1 (p-Drp 1). However, these effects of ICS II were blunted by XAV-939, an inhibitor of Wnt/ß-catenin signaling pathway. In summary, our findings revealed that ICS II could improve neurogenesis and inhibit mitochondrial fission via activation of the Wnt/ß-catenin signaling pathway, which contributed to cognitive function restoration of APP/PS1 mice. This study discovered a novel mechanism involving neurogenesis regulation underlying the therapeutic effects of ICS II against AD.

Profiles of Cytokinins Metabolic Genes and Endogenous Cytokinins Dynamics during Shoot Multiplication In Vitro of Phalaenopsis.

Shoot multiplication induced by exogenous cytokinins (CKs) has been commonly used in Phalaenopsis micropropagation for commercial production. Despite this, mechanisms of CKs action on shoot multiplication remain unclear in Phalaenopsis. In this study, we first identified key CKs metabolic genes, including six isopentenyltransferase (PaIPTs), six cytokinin riboside 5' monophosphate phosphoribohydrolase (PaLOGs), and six cytokinin dehydrogenase (PaCKXs), from the Phalaenopsis genome. Then, we investigated expression profiles of these CKs metabolic genes and endogenous CKs dynamics in shoot proliferation by thidiazuron (TDZ) treatments (an artificial plant growth regulator with strong cytokinin-like activity). Our data showed that these CKs metabolic genes have organ-specific expression patterns. The shoot proliferation in vitro was effectively promoted with increased TDZ concentrations. Following TDZ treatments, the highly expressed CKs metabolic genes in micropropagated shoots were PaIPT1, PaLOG2, and PaCKX4. By 30 days of culture, TDZ treatments significantly induced CK-ribosides levels in micropropagated shoots, such as tZR and iPR (2000-fold and 200-fold, respectively) as compared to the controls, whereas cZR showed only a 10-fold increase. Overexpression of PaIPT1 and PaLOG2 by agroinfiltration assays resulted in increased CK-ribosides levels in tobacco leaves, while overexpression of PaCKX4 resulted in decreased CK-ribosides levels. These findings suggest de novo biosynthesis of CKs induced by TDZ, primarily in elevation of tZR and iPR levels. Our results provide a better understanding of CKs metabolism in Phalaenopsis micropropagation.

[Comparison and health risk assessment of mineral elements in stems and leaves of Dendrobium officinale cultivated with conventional method and mycorrhizal fungi].

This study aims to analyze the variation of the content of mineral elements in stems and leaves of Dendrobium officinale cultivated with conventional method and mycorrhizal fungi, which is expected to lay a basis for safety of stems and leaves of D. officinale. A total of 7 samples from Jiangsu, Fujian, Shanghai, and Zhejiang were collected, which were then cultivated with conventional method and mycorrhizal fungi, separately. The content of 17 mineral elements in stems and leaves was measured by inductively coupled plasma-mass spectrometry(ICP-MS), and the content changes of the mineral elements were analyzed. The health risks of Pb, Cd, Hg, and As in stems were assessed by target hazard quotient(THQ). The results showed that the content of polluting elements in stems and leaves of D. officinale was low, and the content in the plants cultivated with mycorrhizal fungi was reduced. The content of K, Ca, Mg, and P was high in stems and leaves of the species, suggesting that cultivation with mycorrhizal fungi improved the content of other elements irregularly. According to the THQ, the safety risk of stems of D. officinale cultivated with either conventional method or mycorrhizal fungi was low, particularly the D. officinale cultivated mycorrhizal fungi. The results indicated that cultivation with mycorrhizal fungi influenced the element content in stems and leaves of D. officinale. It is necessary to study the culture substrate, processing technology, and the mechanism of the increase or decrease in mineral elements of D. officinale in the future.

miR-338-3p inhibits autophagy in a rat model of allergic rhinitis after PM2.5 exposure through AKT/mTOR signaling by targeting UBE2Q1.

Exposure to fine particulate matter (PM2.5) increases the incidence of allergic rhinitis (AR). microRNA (miRNA) can regulate cell proliferation, invasion and apoptosis. However, the mechanism of miR-338-3p in mediating PM2.5-induced autophagy in AR animal models remains unknown. To explore the mechanism of miR-338-3p in PM2.5-induced autophagy in AR, the human nasal epithelium cells and AR model exposed to PM2.5 were deployed. The results showed that miR-338-3p was down-regulated in both nasal mucosa of PM2.5-exacerbated AR rat models and PM2.5-treated RPMI-2650 cells. Forced expression of miR-338-3p could inhibit autophagy in vitro. miR-338-3p specifically bound to UBE2Q1 3'-untranslated region (3' UTR) and negatively regulated its expression. Overexpression of UBE2Q1 attenuated the inhibitory effects of miR-338-3p on PM2.5-induced autophagy of RPMI-2650 cells through AKT/mTOR pathway. Moreover, our in vivo study found that after administration of agomiR-338-3p in AR rats model, the expression of autophagy-related proteins decreased and nasal symptoms alleviated. In conclusion, this study revealed that miR-338-3p acts as an autophagy suppressor in PM2.5-exacerbated AR by directly targeting UBE2Q1 and affecting AKT/mTOR pathway.

Efficient induction of cytotoxic T lymphocytes in hepatocellular carcinoma using the HLA-A2-restricted survivin peptide in vitro.

Survivin is a newly identified tumour-associated antigen and has been demonstrated to be an excellent target for immunotherapy in several cancers, but its role in hepatocellular carcinoma treatment is still unknown. In this study, survivin-derived peptide-specific cytotoxic T lymphocytes (CTLs) from peripheral blood mononuclear cells of healthy donors were induced by multiple stimulations with HLA-A2- restricted survivin peptide-pulsed T2 cells. The induced CTLs exhibited specific lysis of T2 cells pulsed with the peptide and HLA-A2+ hepatocellular carcinoma cells expressing survivin, while HLA-A2+ hepatocellular carcinoma cell lines that did not express survivin were not recognized by the CTLs. These results suggest that the survivin peptide epitope could be a potential target of specific immunotherapy for HLA-A2+ patients with hepatocellular carcinoma.

Recent advances and new insights in biosynthesis of dendrobine and sesquiterpenes.

Sesquiterpenes are one of the most diverse groups of secondary metabolites that have mainly been observed in terpenoids. It is a natural terpene containing 15 carbon atoms in the molecule and three isoprene units with chain, ring, and other skeleton structures. Sesquiterpenes have been shown to display multiple biological activities such as anti-inflammatory, anti-feedant, anti-microbial, anti-tumor, anti-malarial, and immunomodulatory properties; therefore, their therapeutic effects are essential. In order to overcome the problem of low-yielding sesquiterpene content in natural plants, regulating their biosynthetic pathways has become the focus of many researchers. In plant and microbial systems, many genetic engineering strategies have been used to elucidate biosynthetic pathways and high-level production of sesquiterpenes. Here, we will introduce the research progress and prospects of the biosynthesis of artemisinin, costunolide, parthenolide, and dendrobine. Furthermore, we explore the biosynthesis of dendrobine by evaluating whether the biosynthetic strategies of these sesquiterpene compounds can be applied to the formation of dendrobine and its intermediate compounds. KEY POINTS: • The development of synthetic biology has promoted the study of terpenoid metabolism and provided an engineering platform for the production of high-value terpenoid products. • Some possible intermediate compounds of dendrobine were screened out and the possible pathway of dendrobine biosynthesis was speculated. • The possible methods of dendrobine biosynthesis were explored and speculated.

Network Pharmacology-Based Analysis on the Mechanism of Action of Ephedrae Herba-Cinnamomi Ramulus Couplet Medicines in the Treatment for Psoriasis.

BACKGROUND This study explored the mechanism of action of Ephedrae Herba-Cinnamomi Ramulus couplet medicine (MGCM) at the pharmacological level in the treatment of psoriasis. MATERIAL AND METHODS The active ingredients in MGCM were mined through literature retrieval and the BATMAN-TCM database, and potential targets were predicted. In addition, targets associated with psoriasis were acquired using multiple disease-related databases. Thereafter, an interaction network between candidate MGCM targets and the known psoriasis-associated targets was constructed based on the protein-protein interaction (PPI) data, using the STRING database. Then, the topological parameter degree was determined for mining the core targets for MGCM in the treatment of psoriasis, which also represented the major hubs within the PPI network. In addition, the core networks of targets and ingredients were constructed using Cytoscape software to apply MGCM in the treatment for psoriasis. These core targets were then analyzed for Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathway enrichment using OmicShare. RESULTS The ingredient-target core network of MGCM for treating psoriasis was constructed; it contained 52 active ingredients and corresponded to 19 core targets. In addition, based on enrichment analysis, these core targets were majorly enriched for several biological processes (immuno-inflammatory responses, leukocyte differentiation, energy metabolism, angiogenesis, and programmed cell death) together with the relevant pathways (Janus kinase-signal transducer and activator of transcription, toll-like receptors, nuclear factor kappaB, vascular endothelial growth factor, and peroxisome proliferator-activated receptor), thus identifying the possible mechanism of action of MGCM in treating psoriasis. CONCLUSIONS The present network pharmacology study indicated that MGCM alleviates various pathological factors of psoriasis through multiple compounds, multiple targets, and multiple pathways.

Icarisid II promotes proliferation and neuronal differentiation of neural stem cells via activating Wnt/ß-catenin signaling pathway.

Adult neurogenesis plays a vital role in maintaining cognitive functions in mammals and human beings. Mobilization of hippocampal neurogenesis has been regarded as a promising therapeutic approach to restore injured neurons in neurodegenerative diseases including Alzheimer's disease (AD). Icarisid II (ICS II), an active ingredient derived from Epimedii Folium, has been reported to exhibit multiple neuroprotective effects. In the present study, we investigated the effects of ICS II on the proliferation and differentiation of neural stem cells (NSCs) and amyloid precusor protein (APP)-overexpressing NSCs (APP-NSCs) in vitro. Our results demonstrated that ICS II dose-dependently suppressed apoptosis and elevated viability of APP-NSCs. ICS II (1 µM) potently promoted proliferation and neuronal differentiation of NSCs and APP-NSCs. ICS II (1 µM) significantly upregulated Wnt-3a expression, increased the phosphorylation of glycogen synthase kinase-3ß and enhanced the nuclear transfer of ß-catenin. Moreover, ICS II also promoted astrocytes to secrete Wnt-3a, which positively modulates Wnt/ß-catenin signaling pathway. These findings demonstrate that ICS II promotes NSCs proliferation and neuronal differentiation partly by activating the Wnt/ß-catenin signaling pathway.

High doses of FSH induce autophagy in bovine ovarian granulosa cells via the AKT/mTOR pathway.

Follicle-stimulating hormone (FSH) plays a critical role in follicular growth and granulosa cell function; however, the mechanism by which the aggressive stimulation of FSH leads to poorer oocyte quality and embryo development potential is unclear. In this study, bovine ovarian granulosa cells (BGCs) were challenged with FSH doses (vehicle, 0.1, 1, 10 and 100 ng/ml) to investigate the effects of FSH on BGCs. The results indicated that the relative viability of BGCs was significantly increased in cells challenged with 1 ng/ml FSH, whereas the viability was significantly decreased with 100 ng/ml FSH treatment. The mRNA abundance of FSHR, CYP19, StAR and BAX was significantly upregulated with 1, 10 and 100 ng/ml of FSH, while the BCL-2 mRNA level was downregulated with higher concentrations of FSH (10 and 100 ng/ml). Furthermore, BGC autophagy was detected in cells treated with 10 and 100 ng/ml FSH by MDC staining, and the mRNA abundance of LC3, BECN1, BNIP3, ATG3 and ATG7 was upregulated with increasing FSH concentration. Meanwhile, the protein expression of LC3 was increased in cells treated with 10 and 100 ng/ml FSH. 1 and 10 ng/ml FSH significantly increased E2 production, whereas 10 and 100 ng/ml FSH significantly increased P4 production. FSH significantly inhibited the phosphorylation of AKT in cells treated with higher concentrations (1, 10 and 100 ng/ml), while activating mTOR phosphorylation at concentrations of 10 and 100 ng/ml of FSH. In summary, we can conclude that higher doses of FSH (10 and 100 ng/ml) induce BGC autophagy via the AKT/mTOR signalling pathway.

PFBNet: a priori-fused boosting method for gene regulatory network inference.

BACKGROUND: Inferring gene regulatory networks (GRNs) from gene expression data remains a challenge in system biology. In past decade, numerous methods have been developed for the inference of GRNs. It remains a challenge due to the fact that the data is noisy and high dimensional, and there exists a large number of potential interactions. RESULTS: We present a novel method, namely priori-fused boosting network inference method (PFBNet), to infer GRNs from time-series expression data by using the non-linear model of Boosting and the prior information (e.g., the knockout data) fusion scheme. Specifically, PFBNet first calculates the confidences of the regulation relationships using the boosting-based model, where the information about the accumulation impact of the gene expressions at previous time points is taken into account. Then, a newly defined strategy is applied to fuse the information from the prior data by elevating the confidences of the regulation relationships from the corresponding regulators. CONCLUSIONS: The experiments on the benchmark datasets from DREAM challenge as well as the E.coli datasets show that PFBNet achieves significantly better performance than other state-of-the-art methods (Jump3, GEINE3-lag, HiDi, iRafNet and BiXGBoost).

Genome-wide analysis and prediction of genes involved in the biosynthesis of polysaccharides and bioactive secondary metabolites in high-temperature-tolerant wild Flammulina filiformis.

BACKGROUND: Flammulina filiformis (previously known as Asian F. velutipes) is a popular commercial edible mushroom. Many bioactive compounds with medicinal effects, such as polysaccharides and sesquiterpenoids, have been isolated and identified from F. filiformis, but their biosynthesis and regulation at the molecular level remains unclear. In this study, we sequenced the genome of the wild strain F. filiformis Liu355, predicted its biosynthetic gene clusters (BGCs) and profiled the expression of these genes in wild and cultivar strains and in different developmental stages of the wild F. filiformis strain by a comparative transcriptomic analysis. RESULTS: We found that the genome of the F. filiformis was 35.01 Mb in length and harbored 10,396 gene models. Thirteen putative terpenoid gene clusters were predicted and 12 sesquiterpene synthase genes belonging to four different groups and two type I polyketide synthase gene clusters were identified in the F. filiformis genome. The number of genes related to terpenoid biosynthesis was higher in the wild strain (119 genes) than in the cultivar strain (81 genes). Most terpenoid biosynthesis genes were upregulated in the primordium and fruiting body of the wild strain, while the polyketide synthase genes were generally upregulated in the mycelium of the wild strain. Moreover, genes encoding UDP-glucose pyrophosphorylase and UDP-glucose dehydrogenase, which are involved in polysaccharide biosynthesis, had relatively high transcript levels both in the mycelium and fruiting body of the wild F. filiformis strain. CONCLUSIONS: F. filiformis is enriched in a number of gene clusters involved in the biosynthesis of polysaccharides and terpenoid bioactive compounds and these genes usually display differential expression between wild and cultivar strains, even in different developmental stages. This study expands our knowledge of the biology of F. filiformis and provides valuable data for elucidating the regulation of secondary metabolites in this unique F. filiformis strain.

H2 O2 -induced oxidative stress disrupts mitochondrial functions and impairs migratory potential of human epidermal melanocytes.

Reactive oxygen species (ROS) have already been demonstrated to impede the migratory ability in non-melanocytic cell lines by depleting mitochondrial ATP production. Therefore, understanding the mitochondrial metabolic response to migration in the presence of ROS should be a key to understanding repigmentation in vitiligo. This study aimed to investigate the energy mechanism associated with the ROS-mediated attenuation of melanocyte migration. After melanocytes were pretreated with H2 O2 , their ATP production, migratory ability, ultrastructural changes and Mitochondrial Permeability Potential were analysed. The results showed that, in parallel with the decreased ATP production, the migratory ability of melanocytes was significantly inhibited by oxidative stress. Supplementation with exogenous ATP reversed the suppressed ATP-dependent migration of melanocytes. Melanocytes were then stressed with H2 O2 and Agilent Whole Human Genome microarray analysis identified 763 up-regulated mRNAs and 1117 down-regulated mRNAs. Among them, 11 of the encoded proteins were involved in mitochondrial ATP production and their expression levels were verified. The decreased expression of NADH dehydrogenase 2(ND2) , cytochrome c oxidase 1(COX1) and cytochrome c oxidase 3(COX3) was shown to be involved in the depletion of mitochondrial ATP production, which was coupled with the impaired migratory potential. These results indicate that the migration of melanocytes relies heavily on an inexhaustible supply of ATP from mitochondria.