Potential Applications of Blautia wexlerae in the Regulation of Host Metabolism.

Blautia wexlerae (B. wexlerae) is a strong candidate with the potential to become a next-generation probiotics (NGPs) and has recently been shown for the first time to exhibit potential in modulating host metabolic levels and alleviating metabolic diseases. However, the factors affecting the change in abundance of B. wexlerae and the pattern of its abundance change in the associated indications remain to be further investigated. Here, we summarize information from published studies related to B. wexlerae; analyze the effects of food source factors such as prebiotics, probiotics, low protein foods, polyphenols, vitamins, and other factors on the abundance of B. wexlerae; and explore the patterns of changes in the abundance of B. wexlerae in metabolic diseases, neurological diseases, and other diseases. At the same time, the development potential of B. wexlerae was evaluated in the direction of functional foods and special medical foods.

Evaluating the Role of Postbiotics in the Modulation of Human Oral Microbiota: A Randomized Controlled Clinical Trial.

There is a lack of clinical data to support the effectiveness and safety of postbiotics in the modulation of human oral microbiota and oral health care. Here, volunteers were recruited and randomly assigned to two cohorts: a placebo group (n = 15) and a postbiotic group (n = 16). The placebo group used toothpaste that did not contain postbiotics, while the postbiotic group used toothpaste with postbiotics (3 × 1010 CFU inactivated Lactobacillus salivarius LS97, L. paracasei LC86, and L. acidophilus LA85). Saliva samples were collected at different time points and the immunoglobulin A (IgA) and short-chain fatty acid (SCFA) levels were determined, while the salivary microbiota was analyzed by 16S rRNA amplicon sequencing. The results showed that salivary IgA levels and acetic and propionic acid levels were notably higher in the postbiotic group (P < 0.05), accompanied by an increase in the level of alpha diversity of the salivary microbiota, and these indexes remained high 1 month after discontinuing the use of toothpaste with or without postbiotics. A notable decrease in the relative abundance of the unclassified_Enterobacteriaceae, Klebsiella, Escherichia, etc. in the postbiotic group was accompanied by a notable increase in Ruminofilibacter and Lactobacillus. However, both groups did not cause significant changes in the overall structure of the host salivary microbiota. In conclusion, postbiotics dramatically and consistently improved oral immunity levels and SCFA content in the host. In addition, postbiotics were able to increase the level of microbial alpha diversity and down-regulate the abundance of some harmful microbes without significantly altering the structure of the host salivary microbiota. Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org.cn ) under the registration number ChiCTR2300074088.

Macroscopic model and statistical model to characterize electromagnetic information of a digital coding metasurface.

A digital coding metasurface is a platform connecting the digital space and electromagnetic wave space, and has therefore gained much attention due to its intriguing value in reshaping wireless channels and realizing new communication architectures. Correspondingly, there is an urgent need for electromagnetic information theory that reveals the upper limit of communication capacity and supports the accurate design of metasurface-based communication systems. To this end, we propose a macroscopic model and a statistical model of the digital coding metasurface. The macroscopic model uniformly accommodates both digital and electromagnetic aspects of the meta-atoms and predicts all possible scattered fields of the digital coding metasurface based on a small number of simulations or measurements. Full-wave simulations and experimental results show that the macroscopic model is feasible and accurate. A statistical model is further proposed to correlate the mutual coupling between meta-atoms with covariance and to calculate the entropy of the equivalent currents of digital coding metasurface. These two models can help reconfigurable intelligent surfaces achieve more accurate beamforming and channel estimation, and thus improve signal power and coverage. Moreover, the models will encourage the creation of a precoding codebook in metasurface-based direct digital modulation systems, with the aim of approaching the upper limit of channel capacity. With these two models, the concepts of current space and current entropy, as well as the analysis of information loss from the coding space to wave space, is established for the first time, helping to bridge the gap between the digital world and the physical world, and advancing developments of electromagnetic information theory and new-architecture wireless systems.

Application of mesenchymal stem cell therapy for premature ovarian insufficiency: Recent advances from mechanisms to therapeutics.

The incidence of premature ovarian insufficiency (POI) is increasing worldwide, particularly among younger women, posing a significant challenge to fertility. In addition to menopausal symptoms, POI leads to several complications that profoundly affect female reproductive function and overall health. Unfortunately, current clinical treatment strategies for this condition are limited and often yield unsatisfactory outcomes. These approaches typically involve hormone replacement therapy combined with psychological support. Recently, mesenchymal stem cell (MSC) therapies for POI have garnered considerable attention in global research. MSCs can restore ovarian reproductive and endocrine functions through diverse mechanisms, including controlling differentiation, promoting angiogenesis, regulating ovarian fibrosis, inhibiting apoptosis, enhancing autocrine and paracrine effects, suppressing inflammation, modulating the immune system, and genetic regulation. This editorial offers a succinct summary of the application of MSC therapy in the context of POI, providing evidence for groundbreaking medical approaches that have potential to enhance reproductive health and overall well-being for women.

Mechanisms of Bushen Tiaoxue Granules against controlled ovarian hyperstimulation-induced abnormal morphology of endometrium based on network pharmacology.

Bushen Tiaoxue Granules (BTG) is an empirical Chinese herbal formula that has been used for the treatment of subfertility. The protective effect of BTG on controlled ovarian hyperstimulation (COH)-induced impaired endometrial receptivity has been reported in our previous study. This study aims to explore the mechanisms of BTG on ameliorating abnormal morphology of endometrium based on network pharmacology. Active compounds of BTG were identified via the traditional Chinese medicine systems pharmacology and UPLC-MS technology. The SwissTargetPrediction platform and HERB database were used to screen out the putative targets of BTG. Potential targets of endometrial dysfunction caused by COH were obtained from three GEO databases. Through the STRING database, the protein-protein interaction was carried out according to the cross-common targets of diseases and drugs. GO terms and KEGG pathways enrichment analyses were conducted via the Metascape database. AutoDock Vina was used for docking validation of the affinity between active compounds and potential targets. Finally, in vivo experiments were used to verify the potential mechanisms derived from network pharmacology study. A total of 141 effective ingredients were obtained from TCMSP and nine of which were verified in UPLC-MS. Six genes were selected through the intersection of 534 disease related genes and 165 drug potential targets. Enrichment analyses showed that BTG might reverse endometrial dysfunction by regulating adherens junction and arachidonic acid metabolism. Hematoxylin-eosin staining revealed that BTG ameliorated the loose and edematous status of endometrial epithelium caused by COH. The protein expression of FOXO1A, ß-Catenin and COX-2 was decreased in the COH group, and was up-regulated by BTG. BTG significantly alleviates the edema of endometrial epithelium caused by COH. The mechanisms may be related to adheren junctions and activation of arachidonic acid metabolism. The potential active compounds quercetin, taxifolin, kaempferol, eriodictyol, and isorhamnetin identified from the BTG exhibit marginal cytotoxicity. Both high and low concentrations of kaempferol, eriodictyol, and taxifolin are capable of effectively ameliorating impaired hESC cellular activity.

Preparation of Lycium barbarum Active Glycopeptide and Investigation of Its Apoptotic Effects on Melanoma.

INTRODUCTION: The increasing number of studies have shown that Lycium barbarum polysaccharides possess anti-tumor effects. However, the determination of the active ingredients and their mechanism against melanoma inhibition are still unknown. METHODS: In this study, we aimed to investigate the mechanisms of action of Lycium barbarum active glycopeptide (LBAG) on melanoma. LBAG was extracted and isolated from the fruit of Lycium barbarum using aqueous alcoholic precipitation and identified using ultra-performance liquid chromatography-quadrupole-time of flightmass spectrometry. Various assays including cell apoptosis, cell cycle analysis, colony formation assay, cell scratch test, flow cytometry, and Western blot were performed to evaluate the effects of LBAG on melanoma. RESULTS: The results showed that LBAG has a molecular weight of 10-15 kDa and contains Man, Rha, GlcA, Glc, Gal, and Ara18 amino acids. Treatment with LBAG significantly decreased B16 cell proliferation and induced cell cycle arrest at the G0/G phase, accompanied by the accumulation of reactive oxygen species. Western blot analysis revealed that the phosphorylation of P38-MAPK and AKT, as well as the expression of N-acetyl-Lcysteine, were related to cell apoptosis and cell cycle regulation. In mouse xenografts, LBAG inhibited tumor growth through the P38-MAPK and AKT signaling pathways. CONCLUSION: In conclusion, the anti-melanoma activity of LBAG may induce apoptosis in cancer cells through ROSmediated activation of the P38-MAPK and AKT signaling pathways. These findings provide a foundation for further research on the anti-melanoma potential of LBAG.

Structural elucidation of a non-starch polysaccharides from Lilii Bulbus and its protective effects against corticosterone-induced neurotoxicity in PC12 cells.

Lilii Bulbus is a folk medicine for both culinary and medicinal purpose. In traditional medicine theory, Lilii Bulbus is usually used as an complementary therapy for nourishing the heart and lung, clearing heat in the treatment of mental instability and depression. In this study, NLPS-1a (Mw = 2610 Da, DP = 16), a water-soluble non-starch Lilii Bulbus polysaccharides, was isolated and purified. Structural analysis showed that NLPS-1a mainly contained Man and Glc with a molar ratio of 11.137 and 9.427. The glycosidic linkages of NLPS-1a were 1,3-Manp (59.93%), 1,2-Glcp (37.93%), T-Glcp (1.21%) and T-Manp (0.93%), indicating the highly-linear structures. In addition, NLPS-1a could significantly repair the injury of PC12 cells induced by corticosterone (CORT), reduce Lactate dehydrogenase (LDH) leakage and decrease the cell apoptosis in a dose-dependent manner. Above all, the results indicated that NLPS-1a had protective effects against CORT-induced neurotoxicity in PC12 cells, and might be a natural antidepressant, which enriched the study of the metabolic mechanism between herbal polysaccharides and antidepressant.

Institutional Residence Protects Against Cognitive Frailty: A Cross-Sectional Study.

Based on the complex aging background, more and more older people have to live in an institution in later life in China. The prevalence of cognitive frailty (CF) is more higher in institutions than in communities. Rarely studies were conducted on the relationship between institutional residence and CF. Hence, this study were performed to determine the relationship between institutional residence (living in a nursing home) and CF in older adults. A total of 1004 older community residents and 111 older nursing home residents over 50 years of age from Hefei, Anhui Province, China were recruited. CF included physical frailty (PF) and mild cognitive impairment (MCI). PF was assessed using the Chinese version of the Fried frailty scale, MCI was assessed using the Montreal Cognitive Assessment, and the common associated factors including sedentary behavior, exercise, intellectual activity, comorbidity, medication, chronic pain, sleep disorders, nutritional status and loneliness were analyzed using regression logistic models. Multivariate regression logistic analysis showed that exercise (P = .019, odds ratio [OR] = 0.494, 95% confidence interval [CI]: 0.274-0.891), intellectual activity (P = .019, OR = 0.595, 95% CI: 0.380-0.932), medication use (P = .003, OR = 2.388, 95% CI: 1.339-4.258), chronic pain (P = .003, OR = 1.580, 95% CI: 1.013-2.465) and loneliness (P = .000, OR = 2.991, 95% CI: 1.728-5.175) were significantly associated with CF in community residents; however, only sedentary behavior (P = .013, OR = 3.851, 95% CI: 1.328-11.170) was significantly associated with CF in nursing home residents. Our findings suggest that nursing homes can effectively address many common risk factors for CF, including lack of exercise and intellectual activity, medication use, chronic pain, and loneliness, better than the community setting. Thus, residing in a nursing home is conducive to the intervention of CF.

Fibroblast growth factor 5 protects against spinal cord injury through activating AMPK pathway.

Excessive productions of inflammatory cytokines and free radicals are involved in spinal cord injury (SCI). Fibroblast growth factor 5 (FGF5) is associated with inflammatory response and oxidative damage, and we herein intend to determine its function in SCI. Lentivirus was instilled to overexpress or knockdown FGF5 expression in mice. Compound C or H89 2HCl were used to suppress AMP-activated protein kinase (AMPK) or protein kinase A (PKA), respectively. FGF5 level was significantly decreased during SCI. FGF5 overexpression mitigated, while FGF5 silence further facilitated inflammatory response, oxidative damage and SCI. Mechanically, FGF5 activated AMPK to attenuate SCI in a cAMP/PKA-dependent manner, while inhibiting AMPK or PKA with pharmacological methods significantly abolished the neuroprotective effects of FGF5 against SCI. More importantly, serum FGF5 level was decreased in SCI patients, and elevated serum FGF5 level often indicate better prognosis. Our study identifies FGF5 as an effective therapeutic and prognostic target for SCI.

Impacts of Climate Changes on Geographic Distribution of Primula filchnerae, an Endangered Herb in China.

Primula filchnerae, an endangered plant endemic to China, has drawn people's attention in recent years due to its ornamental value in flower. It was rarely recorded since being described in 1902, but it was rediscovered in 2009 and is now known from a limited number of sites located in Hubei and Shaanxi Provinces. Since the species is still poorly known, a number of unanswered questions arise related to it: How has P. filchnerae responded to past climate change and how might it respond in the future? Why was P. filchmerae so rarely collected during the past century? We assembled geographic coordinates for P. filchnerae through the field surveys and website searches, and then used a maximum entropy model (MaxEnt) to simulate its potential suitable distribution in six periods with varied carbon emission levels by combining bioclimatic and environmental factors. MaxEnt showed that Min Temperature of the Coldest Month (bio6) and Precipitation of the Coldest Quarter (bio19) affected P. filchnerae's distribution most, with an aggregate contribution >60% and suitable ranges above -5 °C and below 40 mm, respectively. We also analyzed potential habitat distribution in various periods with differing impacts of climate change compared to today's suitable habitats, and in most cases, Shaanxi and Sichuan remained the most stable areas and with possible expansion to the north under various carbon emission scenarios, but the 2050s SSP5-8.5 scenario may be an exception. Moreover, we used MaxEnt to evaluate population shifts, with various scenarios indicating that geometric center would be concentrated in Sichuan Province in China. Finally, conservation strategies are suggested, including the creation of protected areas, long-term monitoring, raising public awareness of plant conservation, situ conservation measures, assisted migration, and species introduction. This study demonstrates how P. filchnerae may have adapted to changes in different periods and provides a scientific basis for germplasm conservation and management.

Protein arginine N-methyltransferase 2 plays a noncatalytic role in the histone methylation activity of PRMT1.

Protein arginine N-methyltransferases are a family of epigenetic enzymes responsible for monomethylation or dimethylation of arginine residues on histones. Dysregulation of protein arginine N-methyltransferase activity can lead to aberrant gene expression and cancer. Recent studies have shown that PRMT2 expression and histone H3 methylation at arginine 8 are correlated with disease severity in glioblastoma multiforme, hepatocellular carcinoma, and renal cell carcinoma. In this study, we explore a noncatalytic mechanistic role for PRMT2 in histone methylation by investigating interactions between PRMT2, histone peptides and proteins, and other PRMTs using analytical and enzymatic approaches. We quantify interactions between PRMT2, peptide ligands, and PRMT1 in a cofactor- and domain-dependent manner using differential scanning fluorimetry. We found that PRMT2 modulates the substrate specificity of PRMT1. Using calf thymus histones as substrates, we saw that a 10-fold excess of PRMT2 promotes PRMT1 methylation of both histone H4 and histone H2A. We found equimolar or a 10-fold excess of PRMT2 to PRMT1 can improve the catalytic efficiency of PRMT1 towards individual histone substrates H2A, H3, and H4. We further evaluated the effects of PRMT2 towards PRMT1 on unmodified histone octamers and mononucleosomes and found marginal PRMT1 activity improvements in histone octamers but significantly greater methylation of mononucleosomes in the presence of 10-fold excess of PRMT2. This work reveals the ability of PRMT2 to serve a noncatalytic role through its SH3 domain in driving site-specific histone methylation marks.

Burden and attributable risk factors of ischemic stroke in China from 1990 to 2019: an analysis from the Global Burden of Disease Study 2019.

Background: The epidemiologic characteristics and attributable risk factors of ischemic stroke in China have changed over the past three decades. An up-to-date analysis on deaths, disability-adjusted life-years (DALYs), prevalence, incidence, and attributable risk factors of ischemic stroke for China is needed. This study aims to provide a comprehensive analysis of burden and attributable risk factors of ischemic stroke at national level in China by sex from 1990 to 2019. Methods: This is a secondary analysis of the Global Burden of Disease (GBD) study 2019. All data used in this study was derived from the 2019 GBD study. Deaths, DALYs, prevalence, incidence, and attributable risk factors of ischemic stroke in China by sex from 1990 to 2019 were analyzed. Results: From 1990 to 2019, the age-standardized deaths rate decreased by 3.3%, age-standardized DALYs rate decreased by 4%, age-standardized prevalence rate increased by 33.5%, and age-standardized incidence rate of ischemic stroke in China increased by 34.7%. In 2019, ambient particulate matter pollution became an important risk factor, whereas household air pollution from solid fuels was no longer a major risk factor for ischemic stroke in China. Burden of ischemic stroke was higher in China compared to other regions. Ambient particulate matter pollution among men, and diet high in sodium, smoking, household air pollution from solid fuels among women account for the increased deaths/DALYs due to ischemic stroke in China. Conclusion: Our study revealed that great changes have occurred in burden and attributable risk factors of ischemic stroke in China in the past three decades. Distinct sex-specific differences are observed in burden and attributable risk factors.

Inhibition of tick-borne encephalitis virus in cell cultures by ribavirin.

Tick-borne encephalitis virus (TBEV) belonging to arboviruses is a major member of zoonotic pathogens. TBEV infection causes severe human encephalitis without specific antiviral drugs. Due to its use of antiviral drug against a wide range of viruses, we investigated antiviral effect of ribavirin against TBEV in susceptible human cell lines A549 and SH-SY5Y. Ribavirin displayed minor cytotoxicity on multiple cell lines. Ribavirin obviously impaired TBEV replication and protected the infected cells from cytopathic effect. Importantly, ribavirin markedly inhibited TBEV propagation, as evidenced by impairment of TBEV production and viral RNA replication. Treatment with ribavirin (co-treatment and post-treatment) led to a dose-dependent reduction in TBEV titers as well as the viral RNA levels. Antiviral protein myxovirus resistance A mRNA expression was significantly up-regulated and signal transducer and activator of transcription 3 was activated in TBEV-infected A549 cells upon the ribavirin treatment. Induction of inflammatory cytokine tumor necrosis factor alpha by TBEV was decreased in A549 cells with the treatment of ribavirin, whereas interleukin 1 beta release appeared to be unaffected. These results suggest that ribavirin might represent a promising safe and effective antiviral drug against TBEV.

Structural changes of polysaccharides from Astragulus after honey processing and their bioactivities on human gut microbiota.

BACKGROUND: Astragali Radix (also known as Astragulus) is a traditional medicinal and edible homologous plant for tonifying Qi. Honey-processed Astragalus is a dosage form of Astragali Radix processed with honey, which exhibited better efficacy of tonifying Qi than the raw product. Polysaccharides are their main active components. RESULTS: APS2a and HAPS2a were initially isolated from Astragulus and honey-processed Astragulus. Both of them are highly branched acidic heteropolysaccharides containing ɑ-configuration and ß-configuration glycosidic bonds. The molecular weight and the molecular dimension of HAPS2a decreased and the GalA contained in APS2a was converted to Gal in HAPS2a. The α-configuration galactose residue 1,3,4-α-Galp in the backbone of APS2a was converted to the corresponding ß-configuration galactose residue 1,3,4-ß-Galp in the backbone of HAPS2a and the uronic acid residue T-α-GalpA in the sidechain of APS2a was converted to the corresponding neutral residue T-α-Galp in the side chain of HAPS2a. Bioactivity results showed that HAPS2a had better probiotic effects on Bacteroides ovatus, Bacteroides thetaiotaomicron, Bifidobacterium longum and Lactobacillus rhamnosus strains than APS2a. After degradation, the molecular weights of HAPS2a and APS2a decreased with the changes in their monosaccharide composition. The contents of total short-chain fatty acids (SCFAs) and other organic acids in HAPS2a group were higher than APS2a group. CONCLUSIONS: Two novel high-molecular-weight polysaccharides named APS2a and HAPS2a had different probiotic activities in vitro, which might be due to their structural differences before and after honey processing. Both of them might be possibly used as an immunopotentiator in healthy foods or dietary supplement. © 2023 Society of Chemical Industry.

[Pollution Characteristics and Factors Influencing the Reduction in Ambient PM2.5 in Beijing from 2018 to 2020].

Air quality data from 33 environment sites and five regional sites from 2018 to 2020, as well as meteorological data, were used to research PM2.5 variation,spatial and temporal change, diurnal variation, and heavy pollutions in Beijing. The annual average mass concentrations of PM2.5 in Beijing were 51, 42, and 38 µg·m-3, which showed great progress in air quality improvement. However, the PM2.5 concentration in 2020 was still 8.6% above the national limit value despite a 30.9% decline since 2017. The PM2.5 south-north gradient in Beijing remained throughout the three years, but this pattern showed a less significant trend. The highest monthly mean PM2.5 concentrations in Beijing tended to occur in January-March, with the lowest in August-September. NOx, CO, and PM2.5 concentrations were significantly higher in the heating season than in the non-heating season by 58.4%, 52.9%, and 27.5%, respectively. Diurnal variation showed that greater PM2.5 concentrations were observed at nighttime during the heating season and, conversely, at noontime during the non-heating season. Sixteen pollution episodes occurred in Beijing over the last three years, resulting in 25 heavy pollution days distributed in autumn-winter of 2018-2020. The regional heavy pollution characteristics of PM2.5 in Beijing were significant. Through analysis, a continuous pollution reduction was still the most important reason for the yearly decrease in PM2.5. The concentrations of organic matter, elemental carbon, and crustal matter in the PM2.5 in Beijing decreased by 43.3%, 53.2%, and 51.5% since 2017, respectively, and nitrate, sulfate, and ammonium decreased by 34.2%, 52.2%, and 43.7%.The results showed that the control effect of PM2.5 in Beijing was obvious.

The relationship between gut microbiota and neonatal pathologic jaundice: A pilot case-control study.

Background and objective: Neonatal jaundice is a common clinical disease in neonates. Pathologic jaundice is more harmful to neonates. There are a few studies on the biomarkers of pathologic jaundice and the correlation between gut microbiota and clinical indices. Therefore, we aimed to reveal the characteristics of gut microbiota in pathologic jaundice, provide potential biomarkers for the diagnosis of pathologic jaundice, and find the correlation between gut microbiota and clinical indices. Methods: Fourteen neonates with physiologic jaundice were recruited into a control group (Group A). Additionally, 14 neonates with pathologic jaundice were recruited into a case group (Group B). The microbial communities were analyzed using 16S rDNA sequencing. LEfSe and the differences in the relative abundance of gut microbiota were used to identify different bacteria among the two groups. The ROC curve was used to assess effective biomarkers for pathologic jaundice. Spearman's rank-sum correlation coefficient was used to evaluate the correlation between gut microbiota and clinical indices. Results: There were no differences in the total richness or diversity of gut microbiota between the two groups. At the phylum and genus levels, compared with the control group, Bacteroidetes (p = 0.002) and Braydrhizobium (p = 0.01) were significantly higher, while Actinobacteria (p = 0.003) and Bidfldobacterium (p = 0.016) were significantly lower in the case group. Bacteroidetes were valuable in differentiating pathologic jaundice from physiologic jaundice by the ROC curve, and the area under the ROC curve (AUC) value was 0.839 [95%CI (0.648-0.995)]. In the case group, Bacteroidetes were negatively associated with total bilirubin (TBIL) (p < 0.05). In the control group, Bacteroidetes were positively associated with TBIL (p < 0.05). Conclusion: Bacteroidetes could be used as biomarkers to identify pathologic jaundice and Bacteroidetes are positively associated with bilirubin levels.

Serum glial cell line-derived neurotrophic factor (GDNF) a potential biomarker of executive function in Parkinson's disease.

Objective: Evidence shows that the impairment of executive function (EF) is mainly attributed to the degeneration of frontal-striatal dopamine pathway. Glial cell line-derived neurotrophic factor (GDNF), as the strongest protective neurotrophic factor for dopaminergic neurons (DANs), may play a role in EF to some extent. This study mainly explored the correlation between serum GDNF concentration and EF performance in Parkinson's disease (PD). Methods: This study recruited 45 healthy volunteers (health control, HC) and 105 PD patients, including 44 with mild cognitive impairment (PD-MCI), 20 with dementia (PD-D), and 20 with normal cognitive function (PD-N). Neuropsychological tests were performed to evaluate EF (working memory, inhibitory control, and cognitive flexibility), attention, language, memory, and visuospatial function. All subjects were tested for serum GDNF and homovanillic acid (HVA) levels by ELISA and LC-ESI-MS/MS, respectively. Results: PD-MCI patients showed impairments in the trail making test (TMT) A (TMT-A), TMT-B, clock drawing test (CDT) and semantic fluency test (SFT), whereas PD-D patients performed worse in most EF tests. With the deterioration of cognitive function, the concentration of serum GDNF and HVA in PD patients decreased. In the PD group, the serum GDNF and HVA levels were negatively correlated with TMT-A (r GDNF = -0.304, P < 0.01; r HVA = -0.334, P < 0.01) and TMT-B (r GDNF = -0.329, P < 0.01; r HVA = -0.323, P < 0.01) scores. Serum GDNF levels were positively correlated with auditory verbal learning test (AVLT-H) (r = 0.252, P < 0.05) and SFT (r = 0.275, P < 0.05) scores. Serum HVA levels showed a positively correlation with digit span test (DST) (r = 0.277, P < 0.01) scores. Stepwise linear regression analysis suggested that serum GDNF and HVA concentrations and UPDRS-III were the influence factors of TMT-A and TMT-B performances in PD patients. Conclusion: The decrease of serum GDNF concentration in PD patients was associated with impaired inhibitory control, cognitive flexibility, and attention performances. The changes of GDNF and HVA might synergistically participate in the occurrence and development of executive dysfunction in PD patients.

Research progress on molecular biomarkers of acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common type of adult acute leukemia. The pathophysiology of the disease has been studied intensively at the cellular and molecular levels. At present, cytogenetic markers are an important basis for the early diagnosis, prognostic stratification and treatment of AML. However, with the emergence of new technologies, the detection of other molecular markers, such as gene mutations and epigenetic changes, began to play important roles in evaluating the occurrence and development of diseases. Recent evidence shows that identifying new AML biomarkers contributes to a better understanding of the molecular mechanism of the disease and is essential for AML screening, diagnosis, prognosis monitoring, and individualized treatment response. In this review, we summarized the promising AML biomarkers from four aspects, which contributing to a better understanding of the disease. Of course, it must be soberly aware that we have not listed all biomarkers of AML. Anyway, the biomarkers we mentioned are representative. For example, mutations in TP53, FLT3, and ASXL1 suggest poor prognosis, low remission rate, short survival period, and often require allogeneic hematopoietic stem cell transplantation. The CEBPA double mutation, NPM1 and CBF mutation suggest that the prognosis is good, the remission rate is high, the survival period is long, and the effect of chemotherapy or autotherapy is good. As for other mutations mentioned in the article, they usually predict a moderate prognosis. All in all, we hope it could provide a reference for the precise diagnosis and treatment of AML.

A modified mouse model of haemorrhagic transformation associated with tPA administration after thromboembolic stroke.

Objective: To establish a new mouse model of haemorrhagic transformation associated with delayed tissue-type plasminogen activator (tPA) treatment to provide a novel tool to study therapeutic strategies for haemorrhagic transformation. Methods: Male C57BL/6 mice were subjected to carotid artery thrombosis stimulated with ferric chloride. The thrombus was then mechanically detached to induce migration toward the intracranial circulation. To induce haemorrhagic transformation, mice were intravenously injected with 10 mg/kg tPA 4.5 h after the onset of ischaemia and were sacrificed 24 h after tPA treatment. Results: In this new model, administration of tPA 4.5 h after stroke exacerbated the risk of intracerebral haemorrhage. Thrombolysis with tPA also exacerbated cerebral infarction, brain oedema, blood-brain barrier breakdown, and neurological deficits. However, cerebral blood flow was not significantly affected. Conclusion: The present model is reproducible, easy to perform, and mimics the clinical situation of haemorrhagic transformation after tPA treatment in humans. This modified model can be used as a new tool to test experimental drugs for haemorrhagic transformation associated with delayed tPA administration after an ischaemic stroke.

The hybridization origin of the Chinese endemic herb genus Notopterygium (Apiaceae): Evidence from population genomics and ecological niche analysis.

Hybridization is recognized as a major force in species evolution and biodiversity formation, generally leading to the origin and differentiation of new species. Multiple hybridization events cannot easily be reconstructed, yet they offer the potential to study a number of evolutionary processes. Here, we used nuclear expressed sequence tag-simple sequence repeat and large-scale single nucleotide polymorphism variation data, combined with niche analysis, to investigate the putative independent hybridization events in Notopterygium, a group of perennial herb plants endemic to China. Population genomic analysis indicated that the four studied species are genetically well-delimited and that N. forrestii and N. oviforme have originated by hybridization. According to Approximate Bayesian Computation, the best-fit model involved the formation of N. forrestii from the crossing of N. franchetii and N. incisum, with N. forrestii further backcrossing to N. franchetii to form N. oviforme. The niche analyses indicated that niche divergence [likely triggered by the regional climate changes, particularly the intensification of East Asian winter monsoon, and tectonic movements (affecting both Qinghai-Tibetan Plateau and Qinling Mountains)] may have promoted and maintained the reproductive isolation among hybrid species. N. forrestii shows ecological specialization with respect to their parental species, whereas N. oviforme has completely shifted its niche. These results suggested that the climate and environmental factors together triggered the two-step hybridization of the East Asia herb plants. Our study also emphasizes the power of genome-wide SNPs for investigating suspected cases of hybridization, particularly unravelling old hybridization events.