[Effect of Shikonin on Autophagy and Apoptosis of Human Promyelocytic Leukemia Cells].

OBJECTIVE: To explore the effect of shikonin on autophagy and apoptosis of human promyelocytic leukemia cells and its possible mechanism. METHODS: Human promyelocytic leukemia cells NB4 in the logarithmic growth phase were divided into control group (untreated NB4 cells), shikonin group (0.3 µmol/L shikonin treatment), 740Y-P group (15 µmol/L PI3K/Akt/mTOR pathway activator 740Y-P treatment), shikonin+740Y-P group (0.3 µmol/L shikonin and 15 µmol/L 740Y-P co-treatment), after 24 hours of treatment, the cells were used for subsequent experiments. CCK-8 method was used to detect cell viability, monodansylcadaverine (MDC) staining to detect the aggregation of autophagic vesicles, flow cytometry to detect cell apoptosis, and Western blot to detect the expression of Beclin1, LC3, p62, Bax, cleaved caspase-3, Bcl-2 and PI3K/Akt/mTOR pathway related proteins. RESULTS: Compared with the control group, the purple punctate fluorescence intensity, apoptosis rate, Beclin1, LC3-Ⅱ/LC3-Ⅰ, cleaved caspase-3, and Bax protein expression in NB4 cells were increased in the shikonin group, while OD450 value (24, 48 h) and the expressions of Bcl-2 and p62 proteins were decreased (all P < 0.05). Compared with the control group, the purple punctate fluorescence intensity, apoptosis rate, Beclin1, LC3-Ⅱ/LC3-Ⅰ, cleaved caspase-3, and Bax protein expression in NB4 cells were decreased, while OD450 value (24, 48 h) and the expressions of Bcl-2 and p62 proteins were increased in the 740Y-P group (all P < 0.05). Compared with the shikonin group, the purple punctate fluorescence intensity, apoptosis rate, Beclin1, LC3-Ⅱ/LC3-Ⅰ, cleaved caspase-3, and Bax protein expression in NB4 cells were decreased, while OD450 value (24, 48 h) and the expressions of Bcl-2 and p62 proteins were increased in the shikonin+740Y-P group (all P < 0.05). Compared with the control group, the expression of PI3K/Akt/mTOR pathway related proteins p-PI3K, p-Akt, and p-mTOR in NB4 cells were significantly decreased in the shikonin group, while those in the 740Y-P group were increased (all P < 0.05). Compared with the shikonin group, the expressions of p-PI3K, p-Akt, and p-mTOR proteins in NB4 cells were significantly increased in the shikonin+740Y-P group (all P < 0.05). CONCLUSION: Shikonin may promote autophagy and apoptosis of NB4 cells by inhibiting PI3K/Akt/mTOR pathway.

[Mechanism of ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix regulates HIF-1α signaling pathway mediated by renal hypoxia to ameliorate renal fibrosis in DKD rats].

This study explored the mechanism of the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix in ameliorating renal fibrosis in the rat model of diabetic kidney disease(DKD) based on the expression of hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF) and HIF-1α/platelet-derived growth factor(PDGF)/platelet-derived growth factor receptor(PDGFR) signaling pathways in the DKD rats. After 1 week of adaptive feeding, 50 male SPF-grade Wistar rats were randomized into a blank group(n=7) and a modeling group. After 24 h of fasting, the rats in the modeling group were subjected to intraperitoneal injection of streptozocin and fed with a high-sugar and high-fat diet to establish a DKD model. After modeling, the rats were randomly assigned into model(n=7), low-dose ultrafiltration extract(n=7), medium-dose ultrafiltration extract(n=7), irbesartan(n=8), and high-dose ultrafiltration extract(n=8) groups. After intervention by corresponding drugs for 12 weeks, the general conditions of the rats were observed. The body weights and blood glucose levels of the rats were measured weekly, and the 24 h urinary protein(24hUP) was measured at the 6th and 12th weeks of drug administration. After the last drug administration, the renal function indicators were determined. Masson staining was employed to observe the pathological changes of the renal tissue. The expression of prolyl hydroxylase domain 2(PHD2) and HIF-1α in the renal tissue was detected by immunohistochemistry(IHC). Real-time qPCR was employed to determine the mRNA levels of PHD2, VEGF, PDGF, and PDGFR in the renal tissue. Western blot was employed to determine the protein levels of HIF-1α, VEGF, PDGF, and PDGFR in the renal tissue. The results showed that compared with the model group, drug administration lowered the levels of glycosylated serum protein(GSP), aerum creatinine(Scr), and blood urea nitrogen(BUN) in a dose-dependent manner(P<0.05 or P<0.01) and mitigated the pathological changes in the renal tissue. Furthermore, drug administration up-regulated mRNA level of PHD2(P<0.05 or P<0.01), down-regulated the mRNA levels of VEGF, PDGF, and PDGFR(P<0.05 or P<0.01) and the protein levels of HIF-1α, VEGF, PDGF, and PDGFR(P<0.01) in the renal tissue, and increased the rate of PHD2-positive cells(P<0.01). In conclusion, the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix effectively alleviated the renal fibrosis in DKD rats by inhibiting the expression of key proteins in the HIF-1α signaling pathway mediated by renal hypoxia and reducing extracellular matrix(ECM) deposition.

A Strain-Promoted Divergent Chemical Steroidation Unveils Potent Anti-Inflammatory Pseudo-Steroidal Glycosides.

The development of novel agents with immunoregulatory effects is a keen way to combat the growing threat of inflammatory storms to global health. To synthesize pseudo-steroidal glycosides tethered by ether bonds with promising immunomodulatory potential, we develop herein a highly effective deoxygenative functionalization of a novel steroidal donor (steroidation) facilitated by strain-release, leveraging cost-effective and readily available Sc(OTf)3 catalysis. This transformation produces a transient steroid-3-yl carbocation which readily reacts with O-, C-, N-, S-, and P-nucleophiles to generate structurally diverse steroid derivatives. DFT calculations were performed to shed light on the mechanistic details of the regioselectivity, underlying an acceptor-dependent steroidation mode. This approach can be readily extended to the etherification of sugar alcohols to enable the achievement of a diversity-oriented, pipeline-like synthesis of pseudo-steroidal glycosides in good to excellent yields with complete stereo- and regiospecific control for anti-inflammatory agent discovery. Immunological studies have demonstrated that a meticulously designed cholesteryl disaccharide can significantly suppress interleukin-6 secretion in macrophages, exhibiting up to 99% inhibition rates compared to the negative control. These findings affirm the potential of pseudo-steroidal glycosides as a prospective category of lead agents for the development of novel anti-inflammatory drugs.

The causality between gut microbiome and chronic regional pain: a Mendelian randomization analysis.

Background: Numerous investigations have underscored the causal effect between chronic pain (CP) and gut microbiota, jointly contributing to the onset and development of widespread CP. Nonetheless, there was still uncertainty about the causal effect between gut microbiota and chronic regional pain (CRP). Methods: Genome-wide association study (GWAS) summary data of gut microbial taxa (MiBioGen Consortium: 211 microbiotas and the Dutch Microbiome Project: 207 microbiotas) and eight types of CRP were used to reveal the causal effect between persistent pain in a specific region of the body and gut microbiota. A two-sample bidirectional Mendelian randomization (MR) design was used. In order to ensure the accuracy of the results, multiple sensitivity analyses were employed. Results: This study uncovered significant causal associations between six gut microbial taxa and three types of CRP (forward: Genus Parabacteroides for general pain; Class Bacteroidia, Order Bacteroidales, and Phylum Bacteroidetes for back pain. Reverse: knee pain for Genus Howardella and Order Coriobacteriales) by forward and reverse MR analysis. These findings had been verified by a rigorous Bonferroni correction. Furthermore, this research identified 19 microbial taxa that exhibited potential correlations with four types of CRP. There are no significant or potential gut microbiotas that were associated with other types of CRP, including fascial pain, stomach or abdominal pain, and hip pain. Conclusion: This two-sample bidirectional MR analysis unveiled the causality between gut microbial taxa and eight CRP conditions. The findings reveal the interplay between CRP and 6 gut microbiotas while also delineating 19 potential specific microbial taxa corresponding to diverse locations of persistent pain.

GlcNAc-1,6-anhydro-MurNAc Moiety Affords Unusual Glycosyl Acceptor that Terminates Peptidoglycan Elongation.

Peptidoglycan (PG), an essential exoskeletal polymer in bacteria, is a well-known antibiotic target. PG polymerization requires the action of bacterial transglycosylases (TGases), which couple the incoming glycosyl acceptor to the donor. Interfering with the TGase activity can interrupt the PG assembly. Existing TGase inhibitors like moenomycin and Lipid II analogues always occupy the TGase active sites; other strategies to interfere with proper PG elongation have not been widely exploited. Inspired by the natural 1,6-anhydro-MurNAc termini that mark the ends of PG strands in bacteria, we hypothesized that the incorporation of an anhydromuramyl-containing glycosyl acceptor by TGase into the growing PG may effectively inhibit PG elongation. To explore this possibility, we synthesized 4-O-(N-acetyl-ß-d-glucosaminyl)-1,6-anhydro-N-acetyl-ß-d-muramyl-l-Ala-γ-d-Glu-l-Lys-d-Ala-d-Ala, 1, within 15 steps, and demonstrated that this anhydromuropeptide and its analogue lacking the peptide, 1-deAA, were both utilized by bacterial TGase as noncanonical anhydro glycosyl acceptors in vitro. The incorporation of an anhydromuramyl moiety into PG strands by TGases afforded efficient termination of glycan chain extension. Moreover, the preliminary in vitro studies of 1-deAA against Staphylococcus aureus showed that 1-deAA served as a reasonable antimicrobial adjunct of vancomycin. These insights imply the potential application of such anhydromuropeptides as novel classes of PG-terminating inhibitors, pointing toward novel strategies in antibacterial agent development.

Efficient O- and S-glycosylation with ortho-2,2-dimethoxycarbonylcyclopropylbenzyl thioglycoside donors by catalytic strain-release.

We herein present a strain-release glycosylation method employing a rationally designed ortho-2,2-dimethoxycarbonylcyclopropylbenzyl (CCPB) thioglycoside donor. The donor is activated through the nucleophilic ring-opening of a remotely activable donor-acceptor cyclopropane (DAC) catalyzed by mild Sc(OTf)3. Our new glycosylation method efficiently synthesizes O-, N-, and S-glycosides, providing facile chemical access to the challenging S-glycosides. Because the activation conditions of conventional glycosyl donors and our CCPB thioglycoside are orthogonal, our novel donor is amenable to controlled one-pot glycosylation reactions with conventional donors for expeditious access to complex glycans. The strain-release glycosylation is applied to the assembly of a tetrasaccharide of O-polysaccharide of Escherichia coli O-33 in one pot and the synthesis of a 1,1'-S-linked glycoside oral galectin-3 (Gal-3) inhibitor, TD139, to demonstrate the versatility and effectiveness of the novel method for constructing both O- and S-glycosides.

In silico MS/MS prediction for peptidoglycan profiling uncovers novel anti-inflammatory peptidoglycan fragments of the gut microbiota.

Peptidoglycan is an essential exoskeletal polymer across all bacteria. Gut microbiota-derived peptidoglycan fragments (PGNs) are increasingly recognized as key effector molecules that impact host biology. However, the current peptidoglycan analysis workflow relies on laborious manual identification from tandem mass spectrometry (MS/MS) data, impeding the discovery of novel bioactive PGNs in the gut microbiota. In this work, we built a computational tool PGN_MS2 that reliably simulates MS/MS spectra of PGNs and integrated it into the user-defined MS library of in silico PGN search space, facilitating automated PGN identification. Empowered by PGN_MS2, we comprehensively profiled gut bacterial peptidoglycan composition. Strikingly, the probiotic Bifidobacterium spp. manifests an abundant amount of the 1,6-anhydro-MurNAc moiety that is distinct from Gram-positive bacteria. In addition to biochemical characterization of three putative lytic transglycosylases (LTs) that are responsible for anhydro-PGN production in Bifidobacterium, we established that these 1,6-anhydro-PGNs exhibit potent anti-inflammatory activity in vitro, offering novel insights into Bifidobacterium-derived PGNs as molecular signals in gut microbiota-host crosstalk.

URP20 improves corneal injury caused by alkali burns combined with pathogenic bacterial infection in rats.

Corneal alkali burns often occur in industrial production and daily life, combined with infection, and may cause severe eye disease. Oxidative stress and neovascularization (NV) are important factors leading to a poor prognosis. URP20 is an antimicrobial peptide that has been proven to treat bacterial keratitis in rats through antibacterial and anti-NV effects. Therefore, in this study, the protective effect and influence mechanism of URP20 were explored in a rat model of alkali burn together with pathogenic bacteria (Staphylococcus aureus and Escherichia coli) infection. In addition, human umbilical vein endothelial cells (HUVECs) and human corneal epithelial cells (HCECs) were selected to verify the effects of URP20 on vascularization and oxidative stress. The results showed that URP20 treatment could protect corneal tissue, reduce corneal turbidity, and reduce the NV pathological score. Furthermore, URP20 significantly inhibited the expression of the vascularization marker proteins VEGFR2 and CD31. URP20 also reduced the migration ability of HUVECs. In terms of oxidative stress, URP20 significantly upregulated SOD and GSH contents in corneal tissue and HCECs (treated with 200 µM H2O2) and promoted the expression of the antioxidant protein Nrf2/HO-1. At the same time, MDA and ROS levels were also inhibited. In conclusion, URP20 could improve corneal injury combined with bacterial infection in rats caused by alkali burns through antibacterial, anti-NV, and antioxidant activities.

The causality between gut microbiome and anorexia nervosa: a Mendelian randomization analysis.

Background and aim: Nutrient production by intestinal microbiota corresponds to regulate appetite while gut microbial composition was influenced by diet ingestion. However, the causal relationship between gut microbial taxa and anorexia nervosa (AN) remains unclear. Mendelian Randomization (MR) is a novel research method that effectively eliminates the interference of confounding factors and allows for the exploration of the direct causal effects between exposure and outcome. This study employs MR to explore the causal effect between AN and specific gut microbiome. Methods: Large-scale Genome Wide Association Study (GWAS) data of AN and 211 gut microbes were obtained from the IEU open GWAS project and Mibiogen Consortium. Two-sample MR was performed to determine the causal relationship between gut microbiota and AN. Furthermore, a bi-directional MR analysis was to examine the direction of the causal relations. The Bonferroni correction test was used to adjust potential correlations among microbial taxa. Result: In forward MR analysis, 10specific gut microbial taxa have an impact on the occurrence of AN (the p value of IVW <0.05). The high abundance of Genus Eubacteriumnodatumgroup ID: 11297 (OR:0.78, 95% CI:0.62-0.98, p = 0.035) and Class Melainabacteria ID: 1589 (OR:0.72, 95% CI:0.51-0.99, p = 0.045) may be considered protective factors for AN. But after Bonferroni correction, only Class Actinobacteria ID:419 (OR:1.53, 95% CI:1.19-1.96, p = 0.00089) remained significantly associated and high abundance of Class Actinobacteria ID:419 considered as a risk factor for AN. In the reverse MR analysis, AN influences 8 gut microbial taxa with none-statistically significant associations after adjustment. Conclusion: We identified a significant correlation between AN and 18 microbial taxa which have not been previously reported. Among them, 10 kinds of gut bacteria may affect the occurrence of AN, and the status of AN would affect 8 kinds of gut bacteria. After correction, the Class Actinobacteria ID:419 continued to exert an influence on AN.

The causality between gut microbiome and liver cirrhosis: a bi-directional two-sample Mendelian randomization analysis.

Background and aim: Previous studies have reported an association between gut microbiota and cirrhosis. However, the causality between intestinal flora and liver cirrhosis still remains unclear. In this study, bi-directional Mendelian randomization (MR) analysis was used to ascertain the potential causal effect between gut microbes and cirrhosis. Methods: Large-scale Genome Wide Association Study (GWAS) data of cirrhosis and gut microbes were obtained from FinnGen, Mibiogen consortium, and a GWAS meta-analysis of Alcoholic cirrhosis (ALC). Two-sample MR was performed to determine the causal relationship between gut microbiota and cirrhosis. Furthermore, a bi-directional MR analysis was employed to examine the direction of the causal relations. Result: In MR analysis, we found that 21 gut microbiotas were potentially associated with cirrhosis. In reverse MR analysis, 11 gut microbiotas displayed potentially associations between genetic liability in the gut microbiome and cirrhosis. We found that the family Lachnospiraceae (OR: 1.59, 95% CI:1.10-2.29) might be harmful in cirrhotic conditions (ICD-10: K74). Furthermore, the genus Erysipelatoclostridium might be a protective factor for cirrhosis (OR:0.55, 95% CI:0.34-0.88) and PBC (OR:0.68, 95% CI:0.52-0.89). Combining the results from the MR analysis and reverse MR analysis, we firstly identified the Genus Butyricicoccus had a bi-directional causal effect on PBC (Forward: OR: 0.37, 95% CI:0.15-0.93; Reverse: OR: 1.03, 95% CI:1.00-1.05). Conclusion: We found a new potential causal effect between cirrhosis and intestinal flora and provided new insights into the role of gut microbiota in the pathological progression of liver cirrhosis.

The growth inhibitory effects and non-targeted metabolomic profiling of Microcystis aeruginosa treated by Scenedesmus sp.

The health of the aquatic ecosystem has recently been severely affected by cyanobacterial blooms brought on by eutrophication. Therefore, it is critical to develop efficient and secure methods to control dangerous cyanobacteria, such as Microcystis aeruginosa. In this research, we tested the inhibition of M. aeruginosa growth by a Scenedesmus sp. strain isolated from a culture pond. Scenedesmus sp. culture filtrate that had been lyophilized was added to M. aeruginosa, and cultivation for seven days, the cell density, chlorophyll a (Chl-a) concentration, maximum quantum yield of photosystem II (Fv/Fm), the activities of superoxide dismutase (SOD), catalase (CAT), and the concentration of malondialdehyde (MDA) and glutathione (GSH) were measured. Moreover, non-targeted metabolomics was carried out to provide light on the inhibitory mechanism in order to better understand the metabolic response. According to the results, M. aeruginosa is effectively inhibited by the lyophilized Scenedesmus sp. culture filtrate at a rate of 51.2%. Additionally, the lyophilized Scenedesmus sp. clearly inhibit the photosystem and damages the antioxidant defense system of M. aeruginosa cells, resulting in oxidative damage, which worsens membrane lipid peroxidation, according to changes in Chl-a, Fv/Fm, SOD, CAT enzyme activities and MDA, GSH. Metabolomics analysis revealed that the secondary metabolites of Scenedesmus sp. significantly interfere with the metabolism of M. aeruginosa involved in amino acid synthesis, membrane creation and oxidative stress, which is coherent with the morphology and physiology outcomes. These results demonstrate that the secondary metabolites of Scenedesmus sp. exert algal inhibition effect by breaked the membrane structure, destroyed the photosynthetic system of microalgae, inhibited amino acid synthesis, reduced antioxidant capacity, and eventually caused algal cell lysis and death. Our research provides a reliable basis for the biological control of cyanobacterial blooms on the one hand, and on other hand supply application of non-targeted metabolome on the study of microalgae allelochemicals.

Efficient and versatile formation of glycosidic bonds via catalytic strain-release glycosylation with glycosyl ortho-2,2-dimethoxycarbonylcyclopropylbenzoate donors.

Catalytic glycosylation is a vital transformation in synthetic carbohydrate chemistry due to its ability to expediate the large-scale oligosaccharide synthesis for glycobiology studies with the consumption of minimal amounts of promoters. Herein we introduce a facile and efficient catalytic glycosylation employing glycosyl ortho-2,2-dimethoxycarbonylcyclopropylbenzoates (CCBz) promoted by a readily accessible and non-toxic Sc(III) catalyst system. The glycosylation reaction involves a novel activation mode of glycosyl esters driven by the ring-strain release of an intramolecularly incorporated donor-acceptor cyclopropane (DAC). The versatile glycosyl CCBz donor enables highly efficient construction of O-, S-, and N-glycosidic bonds under mild conditions, as exemplified by the convenient preparation of the synthetically challenging chitooligosaccharide derivatives. Of note, a gram-scale synthesis of tetrasaccharide corresponding to Lipid IV with modifiable handles is achieved using the catalytic strain-release glycosylation. These attractive features promise this donor to be the prototype for developing next generation of catalytic glycosylation.

Morphological change and differential proteomics analysis of gill in Mytilus coruscus under starvation.

Mytilus coruscus is a dominant shellfish in the Yangtze estuary and its adjacent sea area. Food deprivation often occurs during their growth due to fluctuations in algal abundance caused by seasonal freshwater flushing and high-density aquaculture mode. To investigate the coping strategies of M. coruscus to starvation stress, electron microscopy and differential proteomic analysis were performed on the critical feeding organ gill of the mussels after 9 days of starvation. The electron microscopy results showed that the cilia of the mussel gills were dissolved, and the gaps between gill filaments widened under starvation. Differential proteomic analysis revealed that phagocytosis-related proteins such as ATPeV1E, ATPeV1C, LAMP1_2 and CTSL were significantly upregulated, and the phagocytosis pathway was significantly enriched (p < 0.05). In addition, the corin content in gill and myeloperoxidase level as well as the number of dead cells in blood were both significantly increased (p < 0.05). What's more, proteomic data suggested that immune maintenance, cellular transport and metabolism related pathways were significantly enriched, which illustrated an immune and metabolism responses under starvation. This study reveals for the first time that phagocytosis functions as an essential strategy for M. coruscus to cope with starvation, which provides new scientific knowledge and a theoretical basis for understanding the adaptation mechanisms of mussel to starvation and for rational optimization of mussel culture patterns.

Priming effects of nZVI on carbon sequestration and iron uptake are positively mediated by AM fungus in semiarid agricultural soils.

We investigated the priming effect of nanoscale zero-valent iron (nZVI) on carbon sink and iron uptake, and the possible mediation by AMF (arbuscular mycorrhizal fungi, Funneliformis mosseae) in semiarid agricultural soils. Maize seed dressings comprised of three nZVI concentrations of 0, 1, 2 g·kg-1 and was tested with and without AMF inoculation under high and low soil moistures, respectively. The ICP-OES observations indicated that both low dose of nZVI (1 g·kg-1) and high dose of nZVI (2 g·kg-1) significantly increased the iron concentrations in roots (L: 54.5-109.8 %; H: 119.1-245.4 %) and shoots (L: 40.8-78.9 %; H: 81.1-99.4 %). Importantly, the absorption and translocation rate of iron were substantially improved by AMF inoculation under the low-dose nZVI. Yet, the excess nanoparticles as a stress were efficiently relieved by rhizosphere hyphae, and the iron concentration in leaves and stems can maintain as high as about 300 mg·kg-1 while the iron translocation efficiency was reduced. Moreover, next-generation sequencing confirmed that appropriate amount of nZVI clearly improved the rhizosphere colonization of Funneliformis mosseae (p < 0.001) and the development of soil fungal community. Soil observations further showed that the hyphae development and GRSP (glomalin-related soil protein) secretion were significantly promoted (p < 0.05), with the increased R0.25 (< 0.25 mm) by 35.97-41.16 %. As a return, AMF and host plant turned to input more organic matter into soils for microbial growth and Fe uptake, and such interactions became more pronounced under drought stress. In contrast, high dose of nZVI (2 g·kg-1) tended to agglomerate on the surface of hyphae and spores, causing severe deformation and inactivation of AMF symbionts. Therefore, the priming effects of nZVI on carbon sequestration and Fe uptake in agricultural soils were positively mediated by AMF via the feedback loop of the plant-soil-microbe system for enhanced adaptation to global climate change.

Construction and Verification of an RNA-Binding Protein-Associated Prognostic Model for Gliomas.

OBJECTIVE: To construct and verificate an RNA-binding protein (RBP)-associated prognostic model for gliomas using integrated bioinformatics analysis. METHODS: RNA-sequencing and clinic pathological data of glioma patients from The Cancer Genome Atlas (TCGA) database and the Chinese Glioma Genome Atlas database (CGGA) were downloaded. The aberrantly expressed RBPs were investigated between gliomas and normal samples in TCGA database. We then identified prognosis related hub genes and constructed a prognostic model. This model was further validated in the CGGA-693 and CGGA-325 cohorts. RESULTS: Totally 174 differently expressed genes-encoded RBPs were identified, containing 85 down-regulated and 89 up-regulated genes. We identified five genes-encoded RBPs (ERI1, RPS2, BRCA1, NXT1, and TRIM21) as prognosis related key genes and constructed a prognostic model. Overall survival (OS) analysis revealed that the patients in the high-risk subgroup based on the model were worse than those in the low-risk subgroup. The area under the receiver operator characteristic curve (AUC) of the prognostic model was 0.836 in the TCGA dataset and 0.708 in the CGGA-693 dataset, demonstrating a favorable prognostic model. Survival analyses of the five RBPs in the CGGA-325 cohort validated the findings. A nomogram was constructed based on the five genes and validated in the TCGA cohort, confirming a promising discriminating ability for gliomas. CONCLUSION: The prognostic model of the five RBPs might serve as an independent prognostic algorithm for gliomas.

Modeling knot features using branch scars from Mongolian oak (Quercus mongolica).

Wood quality is an important indicator for modern sawmills. Internal wood characteristics can be derived from their correlations with external appearances. In this study, we developed linear regression models to predict knot size from surface features of Mongolian oak (Quercus mongolica) using data collected from 53 trees. For this, manual measurements and X-ray computed tomography scanning technology was respectively used to obtain internal and external features of 1,297 knots. Our results showed that Mongolian oak knots were generally concentrated in the middle part of oak stems, with fewer knots observed at the top and base. The parameters of knot and scar showed significant correlations (P < 0.01), where length and diameter of the corresponding external scar increase with increasing the length and diameter of a knot. The corresponding external scar can be used as an effective indicator to predict the internal value of oak logs. The accuracy of our constructed model is more than 95% when assessed against independent test samples. These models thus can be applied to improve the practical production of oak timber and reduce commercial loss caused by knots. These additional data can improve the estimation of the influence of knots on wood quality and provide a theoretical foundation for investigating the characteristics of hardwood knots.

Clptm1, a new target in suppressing epileptic seizure by regulating GABAA R-mediated inhibitory synaptic transmission in a PTZ-induced epilepsy model.

Disruption of gamma-amino butyric acid type A receptors (GABAA Rs) synaptic clustering and a decrease in the number of GABAA Rs in the plasma membrane are thought to contribute to alteration of the balance between excitatory and inhibitory neurotransmission, which promotes seizure induction and propagation. The multipass transmembrane protein cleft lip and palate transmembrane protein 1 (Clptm1) controls the forward trafficking of GABAA R, thus decaying miniature inhibitory postsynaptic current (mIPSC) of inhibitory synapses. In this study, using a pentylenetetrazol (PTZ)-induced epilepsy rat model, we found that Clptm1 regulates epileptic seizures by modulating GABAA R-mediated inhibitory synaptic transmission. First, we showed that Clptm1 expression was elevated in the PTZ-induced epileptic rats. Subsequently, we found that downregulation of Clptm1 expression protected against PTZ-induced seizures, which was attributed to an increase in the number of GABAA Rγ2s in the plasma membrane and the amplitude of mIPSC. Taken together, our findings identify a new anti-seizure target that provides a theoretical basis for the development of novel strategies for the prevention and treatment of epilepsy.

Transcriptomic insights into the effects of abscisic acid on the germination of Magnolia sieboldii K. Koch seed.

Magnolia sieboldii K. Koch is a deciduous tree species. However, the wild resource of M. sieboldii has been declining due to excessive utilization and seed dormancy. In our previous research, M. sieboldii seeds have morphophysiological dormancy and low germination rates under natural conditions. The aim of the present study was to identify the genes involved in dormancy maintenance. In this study, the germination percentage of M. sieboldii seeds negatively correlated with the content of endogenous abscisic acid (ABA). The hydration of seeds for germination showed three distinct phases. Five key time points were identified: 0 h imbibition (dry seed, GZ), 0 day after imbibition (DAI), 16 DAI, 40 DAI, and 56 DAI. The comprehensive transcript profiles of M. sieboldii seeds treated with ABA and water at the five key germinating stages were obtained. A total of 9641 differentially expressed genes (DEGs) were identified, and 208 and 197 common DEGs were found throughout the ABA and water treatments, respectively. Compared with that in the GZ, 518, 696, 2133, and 1535 DEGs were identified in the SH group at 0, 16, 40 and 56 DAI, respectively. 666, 1725, 1560 and 1415 DEGs were identified in the ABA group at 0, 16, 40, and 56 DAI, respectively. Among the identified DEGs, 12 722 were annotated with GO terms, the top three enriched GO terms were different among the DEGs at 56 DAI in the ABA vs. SH treatments. KEGG pathway enrichment analysis for DEGs indicated that oxidative phosphorylation, protein processing in endoplasmic reticulum, starch and sucrose metabolism play an important role in seed response to ABA. 1926 TFs are obtained and classified into 72 families from the M. sieboldii transcriptome. Results of differential gene expression analysis together with qRT-PCR indicated that phase II is crucial for rapid and successful seed germination. This study is the first to present the global expression patterns of ABA-regulated transcripts in M. sieboldii seeds at different germinating phases.

CIP2A deficiency promotes depression-like behaviors in mice through inhibition of dendritic arborization.

Major depressive disorder (MDD) is a severe mental illness. Decreased brain plasticity and dendritic fields have been consistently found in MDD patients and animal models; however, the underlying molecular mechanisms remain to be clarified. Here, we demonstrate that the deletion of cancerous inhibitor of PP2A (CIP2A), an endogenous inhibitor of protein phosphatase 2A (PP2A), leads to depression-like behaviors in mice. Hippocampal RNA sequencing analysis of CIP2A knockout mice shows alterations in the PI3K-AKT pathway and central nervous system development. In primary neurons, CIP2A stimulates AKT activity and promotes dendritic development. Further analysis reveals that the effect of CIP2A in promoting dendritic development is dependent on PP2A-AKT signaling. In vivo, CIP2A deficiency-induced depression-like behaviors and impaired dendritic arborization are rescued by AKT activation. Decreased CIP2A expression and impaired dendrite branching are observed in a mouse model of chronic unpredictable mild stress (CUMS). Indicative of clinical relevance to humans, CIP2A expression is found decreased in transcriptomes from MDD patients. In conclusion, we discover a novel mechanism that CIP2A deficiency promotes depression through the regulation of PP2A-AKT signaling and dendritic arborization.

Anticoagulation after transjugular intrahepatic portosystemic shunt for portal hypertension: A systematic review and meta analysis.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is widely applied to decrease portal hypertension. Because of the lack of strong evidence, it is controversial whether anticoagulation should be performed after TIPS. This meta-analysis aimed to assess the safety and efficacy of anticoagulation for patients with portal hypertension following TIPS. METHODS: Studies making comparisons between combination treatment and TIPS alone were searched in China National Knowledge Infrastructure, Cochrane Library, PubMed, the Wan Fang electronic databases, and EMBASE, delivered between the earliest accessible date and September 4, 2021. The RevMan version 5.3 was applied to conduct all statistical analyses. I2 index statistic was used to assess heterogeneity. RESULTS: Five eligible studies were selected, and total 707 patients were enrolled. According to the meta-analysis, compared to TIPS alone, TIPS + anticoagulation led to much lower incidence of portal vein thrombosis (PVT; odds ratio [OR] = 0.39, 95% confidence interval [CI] 0.18-0.84, P = .02) as well as low heterogeneity (P = 0.36, I2 = 3%). Other index like the stent dysfunction rate (OR = 1.27, 95% CI 0.71-2.77, P = .42), bleeding rate (OR = 1.27, 95% CI 0.71-2.77, P = .42), and incidence of hepatic encephalopathy (OR = 0.87, 95% CI 0.56-1.36, P = .55) showed no statistical significance. CONCLUSIONS: In certain patients with portal hypertension, anticoagulation following TIPS may not be required. However, for patients who do not have a PVT before TIPS, post-TIPS anticoagulation can decrease the incidence of PVT. Nonetheless, further research is still required.