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APETALA2/ethylene response element binding proteins (AP2/EREBP) are a vital type of TF involved in plant organ development and embryogenesis. In this study we identified 202 Litchi AP2/EREBP TFs from the litchi genome. They were classified into four subfamilies by phylogenetic clustering, including AP2s (20), ERFs (112), DREBs (64), and RAVs (6). Analysis of conserved domains, motifs, gene structure, and genome localization were carried out to investigate the evolutionary features of litchi AP2/EREBPs. Over 35% of DREBs and ERFs involved in the expansion of litchi AP2/EREBPs resulted from tandem duplication. The majority of genomic organizations were conservative, except those of the AP2 subfamily, which had no intron and contained less conservative motif numbers. The expression profiles of litchi AP2/EREBPs in ten tissues were investigated using RNA-Seq data and fifty-nine showed tissue-specific expressions. Their expression patterns were confirmed by qRT-PCR with eight tissues-specificity genes. Six genes related to embryogenesis were identified using the map of orthologous gene interaction between Arabidopsis and litchi. This paper is a comprehensive report on the characteristics of the litchi AP2/EREBP gene superfamily. It will serve to further explore the regulatory mechanisms of AP2/EREBP TFs in the litchi somatic embryogenesis and provide information for litchi molecular breeding.

Background About 20–40 % of autistic people experience a phenomenon of regression. Retinol binding protein 4 (RBP4) plays an important role as an inflammatory neurotrophic adipokine and is a promising mediator of the fat-brain axis. Abnormal fatty acid metabolism and lipid mediators have been reported to be related to the etiological mechanism in autism, and amelioration of impaired lipid metabolism can be recognized as a treatment strategy for autism. The purpose of this study is to explore the relationship between RBP4, lipids, and the autistic regression phenomenon, and to discuss their potentials as biomarkers for the autistic regression phenomenon. Methods A total of 60 autistic individuals (18 with regression phenomenon, 42 without regression phenomenon) (ASD group) and 36 healthy controls were enrolled in this case-control study. The levels of RBP4, total cholesterol (TC), high-density lipoprotein (HDLC), low–density lipoprotein (LDLC), and triglyceride (TG) were measured. Childhood Autism Rating Scale (CARS) is used to assess the severity of autism. Ethical measures were performed in compliance with the current Declaration of Helsinki and written informed consent was obtained from the parents before enrollment of the children and adolescents. Results Compared with control subjects, autistic individuals had lower levels of TC (P = 0.007), RBP4 (P = 0.001), and HDLC (P = 0.027). The levels of RBP4 in ASD group were positively correlated with TG (r = 0.355, P = 0.005), HDLC (r = 0.257, P = 0.047), TG/TC (r = 0.376, P = 0.003) and TG/LDLC (r = 0.363, P = 0.004), and were negatively correlated with CARS (r=-0.296, P = 0.003). Further logistic regression demonstrated that decreased RBP4 concentration was associated with the presentation of the autistic regression phenomenon even after the adjustment of the potential confounding factors. Conclusions Serum RBP4 is associated with the autistic regression phenomenon and the severity of ASD. Further studies are needed to expound whether decreased RBP4 participates in the development of the autistic regression phenomenon.

Methylmercury (MeHg) is a common organic form of mercury in water, which has been linked to several forms of biological toxicity. However, studies on the ecotoxicity risk of long-term exposure to low-dose MeHg are insufficient for the assessment of environmental safety. In the present study, the effects of MeHg on multiple generations (P0-F3) and population of Caenorhabditis elegans were investigated under long-term, low-dose exposure. We investigated the multigenerational toxicity of MeHg by analyzing reproductive and developmental indicators. According to our results, exposure to 100 nM MeHg had little effect on the parental generation (P0) but caused serious reproductive toxicity in the offspring (F1-F3), and the effect of MeHg was aggravated with each passing generation. The genes related to apoptosis and DNA damage were upregulated in the F3 generation. Pearson correlation analysis showed that the changes in these genes were closely related to the apoptosis of gonadal cells. Furthermore, chronic exposure to MeHg (from 100 to 1000 nM group) caused a sharp decline in population size and triggered the "bag of worms" phenotype. Genes related to vulvar development were downregulated in the F3 generation after treatment with 100 nM MeHg. These data suggest that long-term low-dose MeHg exposure adversely affected C. elegans and its offspring and triggered multigenerational toxicity and population discrepancy.

Cytochrome P450 2A6 (CYP2A6) is an important metabolic enzyme and is involved in the progression of hepatocellular carcinoma (HCC). However, its specific function and the mechanism of modulation remain to be elucidated. In this study, we found that CYP2A6 is dramatically downregulated in HCC. CYP2A6 expression is closely associated with pathological grading, histologic grade, hepatitis, vascular metastasis, liver inflammation, and worse prognosis. Reduced expression of CYP2A6 contributes to alternative activation of macrophage polarization and impairs macrophage maturation and phagocytosis. Mechanistically, CYP2A6 participates in arachidonic acid metabolism, initiates 20‐hydroxyeicosatetraenoic acid (HETE) generation, and inhibits epoxyeicosatrienoic acid (EET) generation. Disruption of the equilibrium between 20‐HETE and EETs can induce macrophage polarization, thereby modulating antitumor immunity., Cytochrome P450 2A6 (CYP2A6) has an antitumor role and is dramatically downregulated in HCC. CYP2A6 participates in arachidonic acid metabolism, initiates 20‐hydroxyeicosatetraenoic acid (HETE) generation, and inhibits epoxyeicosatrienoic acid (EET) generation. Disruption of the equilibrium between 20‐HETE and EETs can induce macrophage polarization, thereby modulating antitumor immunity.

We report that the cellular uptake of stable isotope-labeled compounds by bacteria can be probed at the single-cell level using infrared spectroscopy, and this monitors the chemical vibrations affected by the incorporation of "heavy" atoms by cells and thus can be used to understand microbial systems. This presents a significant advancement as most studies have focused on evaluating communities of cells due to the poor spatial resolution achieved by classical infrared microspectrometers, and to date, there is no study evaluating the incorporation of labeled compounds by bacteria at single-cell levels using infrared spectroscopy. The development of new technologies and instrumentations that provide information on the metabolic activity of a single bacterium is critical as this will allow for a better understanding of the interactions between microorganisms as well as the function of individual members and their interactions in different microbial communities. Thus, the present study demonstrates the ability of a novel far-field infrared imaging technique, optical photothermal infrared (O-PTIR) spectroscopy, as a tool to monitor the uptake of 13C-glucose and 15N-ammonium chloride by Escherichia coli bacteria at single-cell levels using spectral signatures recorded via single-point and imaging modes. An additional novelty is that imaging was achieved using six vibrational bands in the amide I and II regions, which were analyzed with chemometrics by employing partial least squares-discriminant analysis to predict 13C/12C and 15N/14N simultaneously.

The BAHD family is involved in different biological roles in plants, including secondary metabolite synthesis, improving abiotic/biotic stress resistance, and influencing fruit quality. However, the knowledge about BAHD in banana, an important fruit crop, is limited. In this study, 46 banana BAHD genes (MaBAHDs) were identified and divided into four groups according to phylogenetic analysis. Most of the MaBAHD genes in the same group presented similar conserved motifs and genetic structures. MaBAHD genes have similar expression patterns in two banana varieties, and more genes showed high expressions in the roots. The comprehensive MaBAHD gene expression patterns obtained from two varieties of banana showed valuable information regarding their participation in fruit development, ripening, and response to abiotic/biotic stresses, suggesting that they play key roles in these processes. The systematic analysis of MaBAHD genes offered basic insight for further gene functional assays and potential applications in genetically improving banana cultivars.

Dental pulp stem cells are dental pulp-derived mesenchymal stem cells that originate from the neural crest. They exhibit greater potential for the treatment of nervous system diseases than other types of stem cells because of their neurogenic differentiation capability and their ability to secrete multiple neurotrophic factors. Few studies have reported Alzheimer's disease treatment using dental pulp stem cells. Rat models of Alzheimer's disease were established by injecting amyloid-β1-42 into the hippocampus. Fourteen days later, 5 × 106 dental pulp stem cells were injected into the hippocampus. Immunohistochemistry and western blot assays showed that dental pulp stem cell transplantation increased the expression of neuron-related doublecortin, NeuN, and neurofilament 200 in the hippocampus, while the expression of amyloid-β was decreased. Moreover, cognitive and behavioral abilities were improved. These findings indicate that dental pulp stem cell transplantation in rats can improve cognitive function by regulating the secretion of neuron-related proteins, which indicates a potential therapeutic effect for Alzheimer's disease. This study was approved by the Animal Ethics Committee of Harbin Medical University, China (approval No. KY2017-132) on February 21, 2017.

Chrysis shanghalensis Smith (Hymenoptera: Chrysididae) is an ectoparasitoid and important natural enemy of Monema flavescens Walker (Lepidoptera: Limacodidae), a serious defoliator of a number of tree species. The external morphology of the antennal sensilla of this parasitoid was examined by scanning electron microscopy, and types and distribution of sensilla were recorded. The antennae of C. shanghalensis were geniculate in shape and composed of a scape with radicula, a pedicel, and a flagellum divided into 11 flagellomeres in males and females. Cuticular pore and 14 types of sensilla were identified on the antennae of both sexes. These included aporous Böhm's bristles, sensilla trichodea 1, 2, and 3 (nonporous), sensilla trichodea 4 (multiporous), two types of sensilla chaetica (nonporous), four morphological types of sensilla basiconica (multiporous), two morphological types of sensilla coeloconica (multiporous), and one type of sensillum campaniforme (nonporous).

The role of Helicobacter_bilis (H.bilis) in the development of inflammatory bowel disease (IBD) and colitis-associated carcinogenesis (CAC) has seldom been investigated. We examined the abundance o...

We describe 4 cases of Chlamydia psittaci pneumonia among medical staff in a coronavirus disease 2019 (COVID-19) screening ward, as well as the experience of dealing with this nosocomial infection event. Atypical pneumonia, in addition to COVID-19, should be considered when clustering cases occur, even during a COVID-19 pneumonia pandemic.

Human adenoviruses (HAdVs) commonly cause many diseases such as respiratory diseases, gastroenteritis, cystitis worldwide. HAdV-3, -7, -4 and emergent HAdV-55 and HAdV-14 are the most important types causing severe respiratory diseases. There is no effective drug available for clinical treatment, and no vaccine available for the general population. Therefore, it is important to investigate the seroprevalence against HAdV for developing novel vaccines and vectors. In this study, we investigated the seroprevalence and titer levels of neutralizing antibodies (NAb) against HAdV-3, -4, -7, -14, -55, and -11 in total 278 healthy populations between 0 months and 49 years of age (228 children and 50 adults) from Guangzhou. In children under the age of 18 years, the seropositive rates were significantly increased against HAdV-3 at 12.07%, 33.96%, and 64.29% and against HAdV-7 at 0%, 18.87%, and 19.05% in age groups of 1–2, 3–5, and 6–17 years, respectively. The seroprevalence was very low (0% ~ 8.1%) for all other four types. In adults aged between 18 and 49 years, HAdV-3, -4, and -7 (> 50.00%) were the most common types, followed by HAdV-14 (38.00%), -55 (34.00%), and -11 (24.00%). Adults tended to have high NAb titers against HAdV-4 and -55. HAdV-55-seropositive donors tended to be HAdV-11- and HAdV-14-seropositive. These results indicated the low level of herd immunity against all six HAdV types in young children, and HAdV-14, -55, -11 in adults from Guangzhou City. Our findings demonstrate the importance of monitoring HAdV types and developing vaccines against HAdV for children and adults.

The accumulation of insoluble amyloid β (Aβ) peptides is one of the pathological changes in Alzheimer's disease (AD), which induced synaptic plasticity impairment and excitatory amino acid toxicity associated with decreased memory function. Xingnaojing (XNJ), a well-known prescription in traditional Chinese medicine, has been used for the treatment of stroke for many years in China. In this study, we aim to investigate the therapeutic effects of XNJ in a hippocampus of Aβ1–42 induced mouse model of AD which showed significant memory loss and impaired synaptic morphology and function. Treatment of XNJ could attenuate spatial and working memory dysfunction, increase dendritic spine density and improve long-term potential (LTP) induction. In addition, XNJ treatment significantly increased the level of N-methyl-d-aspartate receptors (NMDARs) and inhibit the NMDA/α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) ratio in AD mice. XNJ treatment also activated the AKT/mechanistic target of rapamycin (mTOR) pathway, while inhibition of the mTOR pathway by rapamycin could reverse the protective effects of XNJ treatment. In conclusion, XNJ protected against synaptic plasticity and memory impairment in AD mice via the activation of AKT/mTOR signaling pathway, suggesting XNJ as an alternative treatment for AD.

Early diagnosis is a key to improve the prognosis of renal cell carcinoma (RCC); however, reliable RCC biomarkers are lacking in clinical practice. In this study, we used isobaric tags for relative and absolute quantification-based mass spectrometry to identify salivary proteins as biomarkers for the diagnosis of RCC. The objective of this study is to discover biomarkers from saliva by utilizing high-throughput quantitative proteomics approaches. Saliva proteins from 124 RCC patients and healthy individuals were identified and quantified. RCC putative biomarkers were verified by real-time polymerase chain reaction or enzyme-linked immunosorbent assay in a prevalidation sample set. Seventy-one differentially expressed salivary proteins were identified. Serotransferrin, haptoglobin, KRT9, and S100A9, which in previous studies were found to be most closely related to cancers, were selected as putative RCC biomarkers. Haptoglobin and S100A9 were significantly elevated in RCC compared with healthy control samples, although the expression of serotransferrin and KRT9 did not differ between the groups. Furthermore, receiver operating characteristic curves with a cut-off value of 75.49 ng/mL for S100A9 revealed a sensitivity of 87.10% and a specificity of 91.94% for discriminating RCC patients from healthy individuals. Salivary haptoglobin differentiated RCC patients from healthy controls with a sensitivity of 85.48% and specificity of 80.65% (cut-off value 43.02 µg/mL). These results provide experimental evidence to support S100A9 and haptoglobin as potential novel, noninvasive biomarkers for the diagnosis of RCC.

A novel actinobacterium, designated strain HNM0687T, was isolated from mangrove soil samples collected from Hainan Province, PR China and its polyphasic taxonomy was studied. Based on the results of 16S rRNA gene sequence analysis, strain HNM0687T was closely related to Gordonia bronchialis NBRC 16047T (98.7 %), Gordonia rhizosphera NBRC 16068T (98.2 %), Gordonia oryzae RS15-1ST (97.9 %), Gordonia polyisoprenivorans NBRC 16320T (97.7 %) and Gordonia sediminis AMA 120T (97.7 %). Genome-based comparisons revealed a clear distinction in average nucleotide identity values between strain HNM0687T and its closely related strains (74.4–78.3 %). Strain HNM0687T contained meso-diaminopimelic acid, arabinose and galactose in whole-cell hydrolysates. Mycolic acid was present. The menaquinones of strain HNM0687T were MK-9(H2) and MK-7(H2). The phospholipids of the isolate were composed of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. The major fatty acids were C16 : 0, C16 : 1 ω7c/C16 : 1 ω6c, C18 : 010-methyl (TBSA), C18 : 0 and C18 : 1 ω9c. Based on its genotypic, chemotaxonomic and phenotypic characteristics, it is concluded that strain HNM0687T represents a novel species of the genus Gordonia for which the name Gordonia mangrovi sp. nov. is proposed. The type strain is HNM0687T (=CCTCC AA 2019074 T=KCTC 49383 T).

Quantitative assessment of the complex hemodynamic environment in type B aortic dissection (TBAD) through computational fluid dynamics (CFD) simulations can provide detailed insights into the disease and its progression. As imaging and computational technologies have advanced, methodologies have been developed to increase the accuracy and physiological relevance of CFD simulations. This study presents a patient-specific workflow to simulate blood flow in TBAD, utilising the maximum amount of in vivo data available in the form of CT images, 4D-flow MRI and invasive Doppler-wire pressure measurements, to implement the recommended current best practice methodologies in terms of patient-specific geometry and boundary conditions. The study aimed to evaluate and verify this workflow through detailed qualitative and quantitative comparisons of the CFD and in vivo data. Based on data acquired from five TBAD patients, a range of essential model inputs was obtained, including inlet flow waveforms and 3-element Windkessel model parameters, which can be utilised in further studies where in vivo flow data is not available. Local and global analysis showed good consistency between CFD results and 4D-MRI data, with the maximum velocity in the primary entry tear differing by up to 0.3 m/s, and 80% of the analysed regions achieving moderate or strong correlations between the predicted and in vivo velocities. CFD predicted pressures were generally well matched to the Doppler-wire measurements, with some deviation in peak systolic values. Overall, this study presents a validated comprehensive workflow with extensive data for CFD simulation of TBAD.

Adapted plant pathogenic fungi deacetylate chitin to chitosan to avoid host perception and disarm the chitin-triggered plant immunity. Whether plants have evolved factors to counteract this fungal evasion mechanism in the plant-pathogen interface remains obscure. Here, we decipher the underlying mechanism of maize cysteine-rich receptor-like secreted proteins (CRRSPs)-AFP1, which exhibits mannose-binding dependent antifungal activity. AFP1 initials the action by binding to specific sites on the surface of yeast-like cells, filaments, and germinated spores of the biotrophic fungi Ustilago maydis. This could result in fungal cell growth and cell budding inhibition, delaying spore germination and subsequently reducing fungal viability in a mannose-binding dependence manner. The antifungal activity of AFP1 is conferred by its interaction with the PMT-dependent mannosylated chitin deacetylases (CDAs) and interfering with the conversion of chitin. Our finding that AFP1 targets CDAs from pathogenic fungi and nonpathogenic budding yeast suggests a potential application of the CRRSP in combating fungal diseases and reducing threats posed by the fungal kingdom.

In Brassica napus L. (rapeseed), complete genic male sterility (GMS) plays an important role in the utilization of heterosis. Although microRNAs (miRNAs) play essential regulatory roles during bud development, knowledge of how GMS is regulated by miRNAs in rapeseed is rather limited. In this study, we obtained a novel recessive GMS system, CN12AB. The sterile line CN12A has defects in tapetal differentiation and degradation. Illumina sequencing was employed to examine the expression of miRNAs in the buds of CN12A and the fertile line CN12B. We identified 85 known miRNAs and 120 novel miRNAs that were expressed during rapeseed anther development. When comparing the expression levels of miRNAs between CN12A and CN12B, 19 and 18 known miRNAs were found to be differentially expressed in 0.5–1.0 mm buds and in 2.5–3.0 mm buds, respectively. Among these, the expression levels of 14 miRNAs were higher and the levels of 23 miRNAs were lower in CN12A compared with CN12B. The predicted target genes of these differentially expressed miRNAs encode protein kinases, F-box domain-containing proteins, MADS-box family proteins, SBP-box gene family members, HD-ZIP proteins, floral homeotic protein APETALA 2 (AP2), and nuclear factor Y, subunit A. These targets have previously been reported to be involved in pollen development and male sterility, suggesting that miRNAs might act as regulators of GMS in rapeseed anthers. Furthermore, RT-qPCR data suggest that one of the differentially expressed miRNAs, bna-miR159, plays a role in tapetal differentiation by regulating the expression of transcription factor BnMYB101 and participates in tapetal degradation and influences callose degradation by manipulating the expression of BnA6. These findings contribute to our understanding of the roles of miRNAs during anther development and the occurrence of GMS in rapeseed.

Amyloid beta (Aβ)-induced neurotoxicity and oxidative stress plays an important role in the pathogenesis of Alzheimer’s disease (AD). ZL006 is shown to reduce over-produced nitric oxide and oxidative stress in ischemic stroke by interrupting the interaction of neuronal nitric oxide synthase and postsynaptic density protein 95. However, few studies are reported on the role of ZL006 in AD. To investigate whether ZL006 exerted neuroprotective effects in AD, we used Aβ1–42 to treat primary cortical neurons and N2a neuroblastoma cells as an in vitro model of AD. Cortical neurons were incubated with ZL006 or dimethyl sulfoxide for 2 hours and treated with Aβ1–42 or NH3•H2O for another 24 hours. The results of cell counting Kit-8 (CCK-8) assay and calcein-acetoxymethylester/propidium iodide staining showed that ZL006 pretreatment rescued the neuronal death induced by Aβ1–42. Fluorescence and western blot assay were used to detect oxidative stress and apoptosis-related proteins in each group of cells. Results showed that ZL006 pretreatment decreased neuronal apoptosis and oxidative stress induced by Aβ1–42. The results of CCK8 assay showed that inhibition of Akt or NF-E2-related factor 2 (Nrf2) in cortical neurons abolished the protective effects of ZL006. Moreover, similar results were also observed in N2a neuroblastoma cells. ZL006 inhibited N2a cell death and oxidative stress induced by Aβ1–42, while inhibition of Akt or Nrf2 abolished the protective effect of ZL006. These results demonstrated that ZL006 reduced Aβ1–42-induced neuronal damage and oxidative stress, and the mechanisms might be associated with the activation of Akt/Nrf2/heme oxygenase-1 signaling pathways.

Postsynaptic density protein-93 (PSD-93) plays an important role in ischemic brain injury through N-methyl-d-aspartate receptor (NMDAR)–triggered neurotoxicity. GTPase-activating protein for Ras (SynGAP) is a GAP specifically expressed in the central nervous system to regulate nerve development and synaptic plasticity. However, the link between PSD-93 and SynGAP and their role in ischemic brain injury remain elusive. Here, we showed that PSD-93 interacted with SynGAP and mediated SynGAP ubiquitination and degradation following ischemic brain injury. Proteasome inhibitor MG-132 could reverse the decrease of SynGAP protein level in wild-type mice following cerebral ischemia reperfusion through inhibiting SynGAP ubiquitination. Furthermore, NMDA receptor inhibitor MK801 could increase SynGAP protein level in wild-type mice following cerebral ischemia reperfusion. However, in PSD-93 knockout mice, MG-132 or NMDAR inhibitor had no significant effect on SynGAP expression. Both MG-132 and PSD-93 knockout reduced infarct volume and improved neurological deficit in mice at different time points after cerebral ischemia reperfusion. Furthermore, we identified that 670–685 amino acid sequence of SynGAP was essential to the binding of SynGAP to PSD-93, and designed a fusion peptide Tat-SynGAP (670–685aa) that could attenuate ischemic brain damage in wild-type mice. In conclusion, we provide the first evidence that PSD-93 directly interacts with SynGAP and mediates its ubiquitination and degradation to aggravate ischemic brain damage. Tat-SynGAP (670–685aa) may be considered as a candidate for treatment of acute ischemic stroke.

Citrullinated histone H3 (H3Cit) is the product of the conversion of peptidylarginine to citrulline in histone H3. We evaluated the H3Cit level in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) tissues and assessed its association with Beclin1 messenger RNA (mRNA) (a key autophagic regulator). The level of H3Cit was detected by a capture enzyme-linked immunosorbent assay, while Beclin1 mRNA was determined by real-time polymerase chain reaction in 80 HBV-related patients with HCC. We found that the mean level of H3Cit was 72.25 ng/mg in HCC and 44.02 ng/mg in nontumor tissues. The mean HCC/nontumor ratio of Beclin1 mRNA was higher (0.096) in tumor samples than in nontumor specimens (0.056). Specifically, Beclin1 mRNA was elevated in 51 HCC cases (63.75%) and decreased in 29 cases (36.25%). Moreover, the levels of H3Cit and Beclin1 mRNA were significantly associated with vascular invasion and serum AFP levels. A shorter survival (19 months) was associated with a high H3Cit level. We also found increased levels of Beclin1 mRNA in the H3Cit (high) group compared with the H3Cit (low) group. The results implied that elevated histone H3 citrullination is associated with increased Beclin1 expression during the development of HBV-related HCC.

Aims White matter hyperintensity (WMH) is the most common neuroimaging manifestation of cerebral small vessel disease and is related to cognitive dysfunction or dementia. This study aimed to investigate the mechanism and effective indicators to predict WMH‐related cognitive impairment. Methods We recruited 22 healthy controls (HC), 25 cases of WMH with normal cognition (WMH‐NC), and 23 cases of WMH with mild cognitive impairment (WMH‐MCI). All individuals underwent diffusion tensor imaging (DTI) and a standardized neuropsychological assessment. Automated Fiber Quantification was used to extract altered DTI metrics between groups, and partial correlation was performed to assess the associations between WM integrity and cognitive performance. Furthermore, machine learning analyses were performed to determine underlying imaging markers of WMH‐related cognitive impairment. Results Our study found that mean diffusivity (MD) values of several fiber bundles including the bilateral anterior thalamic radiation (ATR), the left inferior fronto‐occipital fasciculus (IFOF), the right inferior longitudinal fasciculus (ILF), and the right superior longitudinal fasciculus (SLF) were negatively correlated with memory function, while that of the anterior component of the right IFOF and the posterior and intermediate component of the right ILF showed significant negative correlation with MMSE and episodic memory, respectively. Furthermore, machine learning analyses showed that the accuracy of recognizing WMH‐MCI patients from the WMH populations was up to 80.5% and the intermediate and posterior components of the right ILF and the anterior component of the right IFOF contribute the most. Conclusions Changes in the properties of DTI may be the potential mechanism of WMH‐related MCI, especially the right IFOF and the right ILF, which may become imaging markers for predicting WMH‐related cognitive dysfunction.

Liver plays an important role in drug metabolism, so studying the grade of maturation of this organ would help to develop more appropriate dosing regimens for paediatric populations. Nevertheless, considering the invasive nature of liver analyses there are obvious ethical boundaries, particularly in babies and children. In this work, we investigated the suitability of blood plasma as an alternative matrix to evaluate the biological age of liver. With this aim, we studied the correlation of plasma and liver metabolomic profiles obtained by HPLC-TOF-MS for piglets of different ages (newborns, neonates and infants). By means of Pearson correlation analysis we observed that 360 and 1784 pairs of metabolite features were significantly correlated in positive and negative ionization mode, respectively. Procrustes analysis was applied in order to assess the similarity of the clustering resulting from the data obtained from the two matrices and the two ionisation modes. The Procrustes distances were low for both ESI+ (0.3753) and ESI- (0.3673) and, hence, liver and plasma are expected to provide similar discriminatory information. Furthermore, we found that Multiblock Principal Component Analysis (MB-PCA) readily allowed us to combine the data obtained from both matrices and to better understand the clustering according to the three study groups. Considering all these results, we suggest that plasma can provide valuable insight into the maturation grade of liver in order to provide accurate dosing in paediatric population.

A new species of the genus Hoplocheylus Atyeo and Baker (Acariformes: Heterostigmata: Tarsocheylidae), H. lindquisti Xu & Zhang sp. nov., is described based on larva, deutonymph, adult male and female specimens collected from the bark of dead Pinus massoniana Lamb. infested with Monochamus alternatus (Coleoptera: Cerambycidae) in Fuzhou city, China. This is the first report of the genus Hoplocheylus and the family Tarsocheylidae in China.

The genus Dioscorea is widely distributed in tropical and subtropical regions, and is economically important in terms of food supply and pharmaceutical applications. However, DNA barcodes are relatively unsuccessful in discriminating between Dioscorea species, with the highest discrimination rate (23.26%) derived from matK sequences. In this study, we compared genic and intergenic regions of three Dioscorea chloroplast genomes and found that the density of SNPs and indels in intergenic sites was about twice and seven times higher than that of SNPs and indels in the genic regions, respectively. A total of 52 primer pairs covering highly variable regions were designed and seven pairs of primers had 80%–100% PCR success rate. PCR amplicons of 73 Dioscorea individuals and assembled sequences of 47 Dioscorea SRAs were used for estimating intraspecific and interspecific divergence for the seven loci: The rpoB‐trnC locus had the highest interspecific divergence. Automatic barcoding gap discovery (ABGD), Poisson tree processes (PTP), and generalized mixed Yule coalescence (GMYC) analysis were applied for species delimitation based on the seven loci and successfully identified the majority of species, except for species in the Enantiophyllum section. Phylogenetic analysis of 51 Dioscorea individuals (28 species) showed that most individuals belonging to the same species tended to cluster in the same group. Our results suggest that the variable loci derived from comparative analysis of plastid genome sequences could be good DNA barcode candidates for taxonomic analysis and species delimitation., We compared genic and intergenic regions of three Dioscorea chloroplast genomes and seven pairs of primers had 80%–100% PCR success rate. Automatic barcoding gap discovery (ABGD), Poisson tree processes (PTP), and generalized mixed Yule coalescence (GMYC) analysis were applied for species delimitation based on the seven loci and successfully identified majority species based on more than 100 Dioscorea individuals from 30 species.

1. Plant-microbe interactions are critical for ecosystem functioning and drive rhizosphere processes. Root exudates are an important soil carbon (C) input, as well as a mechanism for communication between plants and rhizosphere microbes, but are notoriously difficult to extract and characterise. Common methods produce either substantial noise from the soil or do not mimic natural systems. Optimising methods for root exudate collection in soil is crucial for advancing our understanding of root-microbe interactions under changing environmental conditions. 2. Hybrid root exudate collection methods, where plants are grown in soil and transferred to hydroponics for exudate collection after root washing, might offer an ecologically relevant alternative to existing approaches. However, this method causes potential root damage as well as osmosis and subsequent leaking of cell contents. Here, we assessed different ‘root recovery’ periods after root washing and before hybrid root exudate collection, by comparing root exudate quantity and quality with both damaged root extracts and with leachates collected from the intact root-soil system. This was done across three common grassland species representing three functional groups. 3. We found that root exudate profiles of the shortest recovery period (0 days) were similar to damaged root extracts and were very high in C. With an increasing period of root recovery, profiles were more similar to leachates collected from the intact root-soil system, and C concentrations decreased. While both hybrid and leachate collection methods separated species by their root exudate profiles, the hybrid method was less variable in terms of the amount of C measured and provided a more diverse and abundant metabolome with better identification of metabolites. 4. Our results show that a recovery period after root washing of at least 3 days is critical to prevent root damage bias in hybrid collection methods, and that our hybrid method yields exudates that discriminate between species. Our data also suggest that exudates collected with this hybrid method are ecologically valid, which is vital for gaining a mechanistic understanding of their role in ecosystem functioning., Highlights • Root-washing method is suitable for ecologically sound root exudate collection. • It allows accurate measures of exudate quantity and composition. • Damage affects must be accounted for and use of a recovery protocol is recommended. • The method permits identification of metabolite specificity between species. • Leachate complements, provides rhizosphere chemical info and species specificity., Tweetable abstract: We introduce a root-washing method for ecologically sound root exudate collection to minimise root damage and distinguish species.

A link between the scent and color of Narcissus tazetta flowers can be anticipated due to their biochemical origin, as well as their similar biological role. Despite the obvious aesthetic and ecological significance of these colorful and fragrant components of the flowers and the molecular profiles of their pigments, fragrant formation has addressed in some cases. However, the regulatory mechanism of the correlation of fragrant components and color patterns is less clear. We simultaneously used one way to address how floral color and fragrant formation in different tissues are generated during the development of an individual plant by transcriptome-based weighted gene co-expression network analysis (WGCNA). A spatiotemporal pattern variation of flavonols/carotenoids/chlorophyll pigmentation and benzenoid/phenylpropanoid/ monoterpene fragrant components between the tepal and corona in the flower tissues of Narcissus tazetta, was exhibited. Several candidate transcription factors: MYB12, MYB1, AP2-ERF, bZIP, NAC, MYB, C2C2, C2H2 and GRAS are shown to be associated with metabolite flux, the phenylpropanoid pathway to the production of flavonols/anthocyanin, as well as related to one branch of the phenylpropanoid pathway to the benzenoid/phenylpropanoid component in the tepal and the metabolite flux between the monoterpene and carotenoids biosynthesis pathway in coronas. It indicates that potential competition exists between floral pigment and floral fragrance during Narcissus tazetta individual plant development and evolutionary development.

Tea is a worldwide popular drink with high nutritional and medicinal values as it is rich in nutrients, such as polyphenols, amino acids, vitamins, glycosides, and so on. Among them, tea polyphenols (TPs) are the current research hotspot. TPs are known to have multiple biological activities such as anti-oxidation, anti-tumor, anti-inflammation, anti-bacteria, lowering lipid, and liver protection. By reviewing a large number of literatures, we explained the mechanism of TPs exerting biological activity and a wide range of applications. We also discussed the deficiencies and development potential of TPs, in order to provide theoretical reference and scientific basis for the subsequent development and utilization of TPs. PRACTICAL APPLICATIONS: We summarized the bioactivity mechanisms of TPs in anti-tumor, anti-oxidation, antibacterial, anti-inflammatory, lipid-lowering, and liver protection, focused on its application fields in food and medicine, and discussed the deficiency and development potential of current research on TPs, so as to provide a certain convenient way for scholars studying TPs. It is expected to contribute to the subsequent discovery of biological activity and the broadening of the field of TPs.

Testicular damage and testosterone secretion disorder are associated with diabetes mellitus. Quercetin, a common flavonoid, has antioxidant, anti-cancer, and blood sugar lowering effects. Therefore, this study aims to investigate the effect of quercetin on the reproductive system of male rats with diabetes in vivo and in vitro and elucidate its mechanism. Streptozotocin (STZ) induction was used to establish a diabetes model in forty male Sprague Dawley (SD) rats, which were subsequently administered with 20 or 50 mg/kg of quercetin. Leydig cells of rat testes were treated by high glucose (HG) followed by 5 or 10 μM quercetin. Two doses of quercetin increased rat body weight and testicular weight, decreased blood glucose,and inhibited oxidative stress. RT-qPCR and Western blotting revealed that quercetin alleviated STZ-induced testicular damage and promoted testosterone synthesis. Both doses of quercetin reduced ROS and MDA levels, and increased SOD level in HG-treated cells. Both, in vivo and in vitro results confirmed that a high dose of quercetin was more effective. MiR-1306-5p was upregulated in testicular tissue of diabetic rats and HG-treated cells. 17β-hydroxysteroid dehydrogenase (HSD17B7) was a target of miR-1306-5p and HSD17B7 was downregulated in STZ-induced rat tissues and HG-treated cells. HSD17B7 overexpression reversed the increase of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (Grp78) protein levels as well as eIF2α phosphorylation level and promotion of cell apoptosis caused by miR-1306-5p overexpression. Moreover, overexpression of HSD17B7 activated the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) axis in HG-treated cells. In conclusion, quercetin inhibits ER stress and improves testosterone secretion disorder through the miR-1306-5p/HSD17B7 axis in diabetic rats.

Strain HNM0947T, representing a novel actinobacterium, was isolated from the coral Galaxea astreata collected from the coast of Wenchang, Hainan, China. The strain was found to have morphological and chemotaxonomic characteristics consistent with the genus Nocardiopsis . The organism formed abundant fragmented substrate mycelia and aerial mycelia which differentiated into non-motile, rod-shaped spores. Whole-cell hydrolysates contained meso-diaminopimelic acid and no diagnostic sugars. The major menaquinones were MK-10(H8), MK-10(H6) and MK-10(H4). The major phospholipids were phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannosides. The major fatty acids were iso-C16:0, anteiso-C17:0, C18:0, C18:0 10-methyl (TBSA) and anteiso-C15:0. The G+C content was 71.3 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain HNM0947T belonged to the genus Nocardiopsis and shared highest sequence similarity to Nocardiopsis salina YIM 90010T (98.8%), Nocardiopsis xinjiangensis YIM 90004T(98.5%) and Nocardiopsis kunsanensis DSM 44524T (98.3%). The strain HNM0947T was distinguished from its closest type strain by low average nucleotide identity (90.8%) and dDDH values (60.4%) respectively. Based on genotypic, chemotaxonomic and phenotypic characteristics, it was concluded that strain HNM0947T represents a novel species of the genus Nocardiopsis whose name was proposed as Nocardiopsis coralli sp. nov. The type strain was HNM0947T (=CCTCC AA 2020015 T=KCTC 49525 T).

Aims: To evaluate the interrelation between neutrophil to lymphocyte ratio (NLR) coupled with gene signatures, inflammation, and diastolic dysfunction in patients with heart failure (HF) with preserved ejection fraction (HFpEF).Methods: The clinical profile of 172 patients with HFpEF (EF ≥ 50%) and 173 non-HF control individuals was analyzed retrospectively. The association between NLR and HFpEF and the predictive performance of NLR for HFpEF were assessed by the binary logistic regression analysis and the receiver operating characteristic curve (ROC). Multivariate linear regression models further examined the associations between NLR and high-sensitivity C-reactive protein (hs-CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and average septal-lateral E/e', respectively. The freshly isolated neutrophils from 30 HFpEF patients and 42 non-HF controls were subjected to transcriptomic profiling. The biomarkers related to neutrophil activation and inflammation were detected in serum samples.Results: The HFpEF patients in Southeast China were lean and had comorbidity burden and worse cardiac structure/function. Compared with non-HF control individuals, HFpEF patients had a rise in NLR. NLR displayed an independent association with HFpEF [adjusted odds ratio, 2.351; 95% CI, 1.464–3.776; p < 0.001] and it predicted HFpEF with the area under the ROC 0.796 (95% CI, 0.748–0.845, p < 0.001). The positive associations between NLR and hs-CRP, NT-proBNP, and mitral E/e' were found in HFpEF patients. Moreover, patients had significantly elevated serum levels of neutrophil elastase and inflammatory biomarkers, both of which correlated with the mitral E/e' ratio. Finally, multiple molecules that drive neutrophil degranulation and inflammation, such as S100A8/A9/A12 and PADI4, were transcriptionally up-regulated in neutrophils of HFpEF patients.Conclusions: The high NLR coupled with transcriptional activation of neutrophils correlates with systemic inflammation and functional impairment in HFpEF patients, which may suggest a causative role of neutrophils in the pathogenesis of the disease.

In the present study, a fluid-wall model was developed to simulate arterial mass transport of macromolecules in atherosclerosis-prone arteries. To incorporate time-dependent transport processes in the arterial wall, two time-averaged numerical procedures were proposed and compared. Model parameters, especially the transport properties of the arterial wall layers, were estimated using a simulation-based optimisation approach. Furthermore, shear-dependent transport properties, such as hydraulic conductivity and permeability were derived from relevant experimental data in the literature to incorporate the shear-dependence of trans-endothelial transport. The mathematical model and corresponding parameters were tested in idealised arterial geometries as preliminary investigations. The model was then applied to a patient-specific case, albumin transport in a human right coronary artery. The main outcomes of this study include the following. 1) The determination of four sets of model parameters, including albumin transport parameters under transmural pressure of 70 mmHg, LDL transport parameters under transmural pressures of 70 mmHg, 120 mmHg, and 160 mmHg. It was shown that the simulation-based optimisation approach led to much better parameter estimations than existing methods. 2) Preliminary model tests showed that the conventional steady flow assumption in the arterial mass transport models may not be adequate, especially when the bulk flow is highly disturbed. The LFTA numerical procedures provided an efficient way to incorporate the effects of flow pulsatility on shear-dependent trans-endothelial transport. Results suggested that the influence of transient haemodynamic conditions on macromolecular transport can be modelled as a time-averaged effect. 3) Albumin accumulation in the subendothelial layer was found to be co-localised with low WSS, implying that the arterial wall exposed to low WSS is atherosclerosis-prone due to a greater lipid accumulation. The accumulation was mainly due to a greater influx in the low WSS regions where the endothelium is more permeable. A number of limitations existed in the present study, including the use of a vascular scale model, parameter-related limitations, and limitations in the time-averaged numerical procedures.

Akt signaling has been associated with adult neurogenesis in the hippocampal dentate gyrus (DG). We reported cognitive dysfunction in Akt3 knockout (Akt3-KO) mice with the down-regulation of mTOR activation. However, little is known about the effects of Akt3 signaling on hippocampal neurogenesis. Herein, we show that progenitor cells, neuroblasts, and mature newborn neurons in hippocampal DG expressed Akt3 protein. The Akt3 phosphorylation in hippocampal DG was increased after voluntary wheel running for 7 days in wild-type mice (running WT mice), but not in Akt3-KO mice (running Akt3-KO mice). Subsequently, we observed that the proliferation of progenitor cells was suppressed in Akt3-KO mice and the mTOR inhibitor rapamycin-treated mice, whereas enhanced in running WT mice rather than running Akt3-KO mice. Neurite growth of neuroblasts was impaired in Akt3-KO mice and rapamycin-treated mice. In contrast, neither differentiation of progenitor cells nor migrating of newly generated neurons was altered in Akt3-KO mice or running WT mice. The levels of p70S6K and 4EBP1 phosphorylation were declined in Akt3-KO mice and elevated in running WT mice depending on mTOR activation. Furthermore, telomerase activity, telomere length, and expression of telomerase reverse transcriptase (TERT) were decreased in Akt3-KO mice but increased in running WT mice rather than running Akt3-KO mice, which required the mTOR activation. The study provides in vivo evidence that Akt3-mTOR signaling plays an important role in the proliferation of progenitor cells and neurite growth through positive regulated TERT expression and activation of p70S6K and 4EBP1.

Hyperlipidemia is a common metabolic disorder and regarded as one of the main risk factors for cardiovascular disease. The gut microbiota has been identified as a potential contributor to hyperlipidemia as it can greatly regulate bile acid metabolism. Linderae radix is a natural medicine widely used in the treatment of a variety of diseases and is also a common drug for hyperlipidemia. Recently, the lipid-lowering effect of Linderae radix are receiving increasing attention but the underlying mechanism remains unknown. The study aimed to investigate the effects of Linderae radix ethanol extract (LREE) on gut microbiota in rats with hyperlipidemia syndrome. We established a hyperlipidemia rat model using a high-fat diet and used LREE as the intervention. Blood lipid levels and pathological examination were measured to assess the effects of LREE on hyperlipidemia. The gut microbiota was determined by 16s rDNA sequencing and the bile acid metabolism-related proteins were detected by western blot to discover the underlying correlations. The results show that LREE lowered TC, TG, and LDL levels effectively, and it also alleviated liver injury by reducing ALT and AST activity. Meanwhile, LREE improved gut microbiota disturbance caused by HFD via increasing intestinal microbiota diversity and changing the abundance of the Firmicutes, Bacteroidetes, and Actinobacteria. In addition, LREE can increase bile acid reabsorption and promote fecal excretion through farnesoid X receptor (FXR), apical sodium-dependent bile acid transporter (ASBT), organic solute transporter alpha (OST-α), and cytochrome P450 family 7 Subfamily A Member 1 (CYP7A1) thus restoring abnormal bile acid metabolism caused by hyperlipidemia.

Adenomyosis is one of the most common gynecological disorders that the molecular events underlying its pathogenesis remain not fully understood. Prior studies have shown that endometrial stromal cells (ESCs) played crucial roles in the pathogenesis of adenomyosis. In this study, we utilized two-dimensional gel electrophoresis combined with protein identification by mass spectrometry (2D/MS) proteomics analysis to compare the differential protein expression profile between the paired eutopic and ectopic ESCs (EuESCs and EcESCs) in adenomyosis, and a total of 32 significantly altered protein spots were identified. Among which, the expression of LIM and SH3 protein 1 (LASP1) was increased significantly in EcESCs compared to EuESCs. Immunohistochemical assay showed that LASP1 was overexpressed in the stromal cells of ectopic endometriums compared to eutopic endometriums; further functional analyses revealed that LASP1 overexpression could enhance cell proliferation, migration and invasion of EcESCs. Furthermore, we also showed that the dysregulated expression of LASP1 in EcESCs was associated with DNA hypermethylation in the promoter region of the LASP1 gene. However, the detailed molecular mechanisms of enhancing cell proliferation, invasion and migration caused by upregulated LASP1 in adenomyosis needs further study. For the first time, our data suggested that LASP1 plays important roles in the pathogenesis of adenomyosis, and could serve as a prognostic biomarker of adenomyosis.

A new phenolic derivative, artopithecin K (1), was isolated from the twigs of Artocarpus pithecogallus. Its structure was elucidated based on extensive spectroscopic analyses. Compound 1 was evaluated for the inhibitory activity against tyrosinase.

Six new (1-6) and two known (7 and 8) indole alkaloids were produced by the marine fish-derived fungus Chaetomium globosum 1C51 through biotransformation. The structures of these alkaloids were elucidated by a combination of MS, NMR, and X-ray crystallography analyses. Chaetoindolone A (1) was shown to inhibit the growth of the rice-pathogenic bacteria Xanthomonas oryzae pv. oryzae (xoo) both in vitro and in vivo. Chaetogline A (7) was found to be fungicidal against Sclerotinia sclerotiorum, a pathogen causing rape sclerotinia rot. Collectively, this work provides access to new indole alkaloids with potential agrochemical significance.

Background: Stanniocalcin 2 (STC2) expression is upregulated under multiple stress conditions including hypoxia, nutrient starvation and radiation. Overexpression of STC2 correlates with tumor progression and poor prognosis. Purpose: We previously demonstrated that overexpression of STC2 in nasopharyngeal carcinomas (NPC) positively correlates with radiation resistance and tumor metastasis, two major clinical obstacles to the improvement of NPC management. However, it remains elusive whether STC2 expression is a critical contributing factor for post-radiation survival and metastasis of NPC cells. Materials and methods: Using the radiation resistant CNE2 cell line as a model, we examined the importance of STC2 expression for post-radiation survival, migration and invasion. Here, we report the establishment of STC2 knockout lines (CNE2-STC2-KO) using the CRISPR/Cas9-based genome editing technique. Results: Compared with the parental line, STC2-KO cells showed similar proliferation and morphology in normal culture conditions, and loss of STC2 did not compromise the cell tumorigenicity in nude mice model. However, STC2-KO lines demonstrated increased sensitivity to X-radiation under either normoxic or hypoxic conditions. Particularly, upon X-radiation, parental CNE2 cells only slightly whereas STC2-KO cells remarkably decreased the migration and invasion ability. Cell cycle analysis revealed that loss of STC2 accumulated cells in G1 and G2/M phases but decreased S-population. Conclusion: These data indicate that the expression of STC2, which can be stimulated by metabolic or therapeutic stresses, is one important factor to promote survival and metastasis of post-radiation NPC cells. Therefore, targeting STC2 or relative downstream pathways may provide novel strategies to overcome radiation resistance and metastasis of NPC.

Background: The goal of this study was to identify the physiological factors related to the blood concentration of lithium in Chinese Han patients with bipolar disorder (BD). Materials and methods: A total of 186 Chinese Han patients with BD were assessed. Patients were recruited from the Anhui Mental Health Center. The concentrations of serum lithium were measured by a Dimension RxL Max biochemistry analyzer. Physiological factors, including body weight, body mass index (BMI), and routine laboratory parameters, were collected. Relationships between the serum lithium concentration and relevant clinical data were analyzed by Pearson correlation tests, and the independent relationships were determined by multivariate linear regression analysis. Results: Pearson correlation analysis showed that serum lithium concentrations were positively correlated with creatinine concentrations (r=0.147, P=0.046), Mg2+ concentrations (r=0.151, P=0.04), and the percentage of neutrophils (r=0.178, P=0.015) and negatively correlated with high-density lipoprotein (HDL) concentrations (r=-0.142, P=0.05), apolipoprotein A1 concentrations (r=-0.169, P=0.02), and Na+ concentrations (r=-0.148, P=0.046) in 186 patients with BD. Furthermore, multivariate linear regression analysis showed that serum lithium concentrations were negatively associated with Na+ concentrations and positively associated with the percentage of neutrophils. Conclusion: These results suggest that physiological factors, including creatinine, HDL, apolipoprotein A1, Na+, and Mg2+ concentrations and percentage of neutrophils, might be related to serum lithium concentrations and provide a basis for parameter selection of lithium population pharmacokinetics in Chinese Han patients with BD.

A Autosomal-dominant ELANE mutations are the most common cause of severe congenital neutropenia. Although the majority of congenital neutropenia patients respond to daily granulocyte colony stimulating factor, approximately 15 % do not respond to this cytokine at doses up to 50 μg/kg/day and approximately 15 % of patients will develop myelodysplasia or acute myeloid leukemia. “Maturation arrest,” the failure of the marrow myeloid progenitors to form mature neutrophils, is a consistent feature of ELANE associated congenital neutropenia. As mutant neutrophil elastase is the cause of this abnormality, we hypothesized that ELANE associated neutropenia could be treated and “maturation arrest” corrected by a CRISPR/Cas9-sgRNA ribonucleoprotein mediated ELANE knockout. To examine this hypothesis, we used induced pluripotent stem cells from two congenital neutropenia patients and primary hematopoietic stem and progenitor cells from four congenital neutropenia patients harboring ELANE mutations as well as HL60 cells expressing mutant ELANE. We observed that granulocytic differentiation of ELANE knockout induced pluripotent stem cells and primary hematopoietic stem and progenitor cells were comparable to healthy individuals. Phagocytic functions, ROS production, and chemotaxis of the ELANE KO (knockout) neutrophils were also normal. Knockdown of ELANE in the mutant ELANE expressing HL60 cells also allowed full maturation and formation of abundant neutrophils. These observations suggest that ex vivo CRISPR/Cas9 RNP based ELANE knockout of patients’ primary hematopoietic stem and progenitor cells followed by autologous transplantation may be an alternative therapy for congenital neutropenia.

Background: Resistance to docetaxel is a major obstacle to effective treatment of breast cancer. Exosomal microRNAs (miRNAs) have recently been introduced in cell-to-cell transmission of chemoresistance between heterogeneous populations of tumor cells with diverse drug sensitivity. However, a systematic evaluation of the exosomal miRNA signature remains largely unclear. Method: miRNA expression profiles in exosomes from docetaxel-resistant (D/exo) and parental sensitive breast cancer cells (S/exo) were assessed using microarray. Bioinformatics analysis was performed to predict target genes of the dysregulated miRNAs and to uncover their potential roles in chemoresistance formation. Signaling pathways, gene ontology terms, transcription factors, protein-protein interactions, and hub genes were also constructed. Results: The selected exosomal miRNAs could modulate target genes responsible for MAPK, TGF-beta, Wnt, mTOR, and PI3K/Akt signaling pathways. Function enrichment analysis revealed the involvement of target genes in transcription regulation, protein phosphorylation, kinase activity, and protein binding. Enriched transcription factors including SP1, SP4, and EGR1 were obtained and a protein-protein interaction network was established. The hub genes for up-expressed and down-expressed exosomal miRNAs such as CCND1 and PTEN were identified. Conclusion: This bioinformatics study provides a comprehensive view of the function of dysregulated exosomal miRNAs, and may help us to understand exosome-mediated resistance transmission and overcome docetaxel resistance in future breast cancer therapy.

OCT4 is a key regulator in maintaining the pluripotency and self-renewal of embryonic stem cells (ESCs). Human OCT4 gene has three mRNA isoforms, termed OCT4A, OCT4B and OCT4B1. The 190-amino-acid protein isoform (OCT4B-190) is one of the major products of OCT4B mRNA, the biological function of which is still not well defined. Recent evidence suggests that OCT4B-190 may function in the cellular stress response. The glycogen synthase kinase-3β (GSK-3β) and histone deacetylase 6 (HDAC6) are also key stress modulators that play critical roles in the ischemic cascades of stroke. Hence, we here further investigated the effects of OCT4B-190 in the experimental stroke, and explored the underlying roles of GSK-3β and HDAC6. We found that OCT4B-190 overexpression enhanced neuronal viability at 24 h after oxygen-glucose deprivation (OGD) treatment. Moreover, in male C57BL/6 mice subjected to transit middle cerebral artery occlusion (MCAO), OCT4B-190 overexpression reduced infarct volume and improved neurological function after stroke. Notably, we found spatio-temporal alterations of GSK-3β and HDAC6 in the ischemic cortex and striatum, which were affected by adenovirus-mediated OCT4B-190 overexpression. OCT4B-190 demonstrated similar impacts on neuronal cultures in vitro, downregulating OGD-induced GSK-3β activity and HDAC6 expression. In addition, we found that GSK-3β and HDAC6 were co-expressed in the cytoplasm of neurons, and OCT4B-190 had an effect on interactions between GSK-3β and HDAC6 in neuronal cultures subjected to OGD treatment. These findings suggest that OCT4B-190 exerts neuroprotection in the experimental stroke potentially by regulating actions of GSK-3β and HDAC6 simultaneously, which may be an attractive therapeutic strategy for ischemic stroke.

The nature of muscle-bone crosstalk has been historically considered to be only mechanical, where the muscle is the load applier while bone provides the attachment sites. However, this dogma has been challenged with the emerging notion that bone and muscle act as secretory endocrine organs affect the function of each other. Biochemical crosstalk occurs through myokines such as myostatin, irisin, interleukin (IL)-6, IL-7, IL-15, insulin-like growth factor-1, fibroblast growth factor (FGF)-2, and β-aminoisobutyric acid and through bone-derived factors including FGF23, prostaglandin E(2), transforming growth factor β, osteocalcin, and sclerostin. Aside from the biochemical and mechanical interaction, additional factors including aging, circadian rhythm, nervous system network, nutrition intake, and exosomes also have effects on bone-muscle crosstalk. Here, we summarize the current research progress in the area, which may be conductive to identify potential novel therapies for the osteoporosis and sarcopenia, especially when they develop in parallel.

Introduction: Schizophrenia has a strong genetic basis. It is reported that the matrix metalloproteinase-9 (MMP-9) −1562C/T polymorphism (rs3918242) may be associated with schizophrenia; ho...

Nosocomial infections caused by Acinetobacter baumannii are associated with high mortality, especially among critically ill patients. A. baumannii is highly resistant to long-term starvation, desiccation, disinfecting agents, and antibiotics, and its negative impact on the cardiology patients is particularly severe. Thus, the present study aimed at the detection of molecular markers of antibiotic resistance in A. baumannii infecting patients in a hospital cardiology unit. Drug susceptibility of 100 A. baumannii strains obtained from the patients of The Second People's Hospital of Futian District was determined, and the presence of genes coding for proteins implicated in antibiotic resistance was evaluated by conventional PCR and real-time PCR. Most of the strains found to be multi-drug resistant and strains not responding to meropenem exhibited a high degree of homology. The resistant strains expressed two genes coding for class D β-lactamases: OXA-51 and OXA-23. Moreover, the AdeB gene, coding for a component of the AdeABC active efflux pumps, was also harbored in a vast majority of meropenem-resistant A. baumannii strains. The obtained results indicate that the recognition of specific genes responsible for the resistance by molecular biology techniques provide a rapid method for identification of A. baumannii strains that do not respond to treatment with antibiotics, an issue of critical importance for cariology patients.

BACKGROUND Avicularin (AL, quercetin-3-alpha-l-arabinofuranoside), a glycoside of quercetin, has been reported to display diverse pharmacological properties. The present study aimed to investigate whether AL has an anti-depressant-like effect on a mouse model of depression induced by chronic unpredictable mild stress (CUMS). MATERIAL AND METHODS A mouse model of depression was established and treated with different concentrations of AL (1.25, 2.5 or 5.0 mg/kg/d) and fluoxetine (20 mg/kg/d). Then, behavioral tests - sucrose preference test (SPT), forced swimming test (FST), and the tail suspension test (TST) - were performed. The levels proinflammatory cytokines - interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-alpha (TNF-alpha) - in the hippocampi of mice were detected by enzyme-linked immunosorbent assay (ELISA). Apoptosis of hippocampal neuronal cells was determined using flow cytometry. Expression levels of phosphorylated (p)-MEK1/2, p-ERK1/2, p-NF-kappaB (p-p65), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Caspase3, and B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) were measured by Western blot assay or/and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. RESULTS The results showed that AL significantly relieved CUMSinduced depressive-like behaviors. Compared with the model mice, AL treatment significantly increased the sucrose preference of the mice, and the immobility time in the FST and the TST were shortened. We also found that AL decreased CUMS-induced increases in the levels of IL-1ß, IL-6, and TNF-alpha in the hippocampi of mice. AL significantly decreased the apoptosis rate of hippocampal neuronal cells in mice, which was increased by CUMS. Furthermore, activation of the MEK/ERK/NF-kappaB pathway induced by CUMS was inhibited by AL treatment. CONCLUSIONS Our results show the anti-depressant-like effects of AL on CUMS-induced depression in a mouse model.

The objective of this study was to develop a new type of feedstuff by utilizing probiotics to transform agricultural byproducts to meet the livestock feed shortage. In this study, peanut hull powder (PHP) was used as the fermentation substrate, which was inoculated with 18 kinds of feed probiotics combined with two kinds of nutritional additives. The desired value formula was used to select the strains suitable for fermentation of PHP, and the strains were combined as multi-culture starters. We compared the changes of the chemical composition and bacterial flora before and after the fermentation, which provided a theoretical basis for the establishment and quality evaluation of the system of PHP fermentation. The result shows that inoculation with CM6 together with nutrients co-fermenting clearly raised the content of organic acid, CP and WSC in the PHP and effectively inhibited the growth of harmful microorganisms such as Enterobacter and Fusarium.

Streptomyes spongiicola HNM0071T is a novel marine sponge-associated actinomycete with potential to produce antitumor agents including staurosporine and echinomycin. Here, we present the complete genome sequence of S. spongiicola HNM0071, which consists of a linear chromosome of 7,180,417 bp, 5669 protein coding genes, 18 rRNA genes, and 66 tRNA genes. Twenty-seven putative secondary metabolite biosynthetic gene clusters were found in the genome. Among them, the staurosporine and echinomycin gene clusters have been described completely. The complete genome information presented here will enable us to investigate the biosynthetic mechanism of two well-known antitumor antibiotics and to discover novel secondary metabolites with potential antitumor activities.

Fatty alcohol is considered as a promising clean fuel alternative to fossil fuel. In this study, we developed a facile and robust multiple enzyme complex of lipase (LIP), carboxylic acid reductase (CAR) and aldehyde reductase (AHR) based on cohesin-dockerin specific interaction and E. coli-ice nucleation protein (INP) surface assembly for highly efficient conversion of triacylglycerols (TAGs) to fatty alcohols. The proximity effect, customized ratio and positional arrangement of the three enzymes were readily genetically generated. The optimized cell associated three enzyme complex gave 73% of conversion yield, and showed significantly improved stability in higher temperature, acidic/alkaline environments, polar organic solvents, high concentration of substrate, and good recyclability in successive biotransformations. The three enzyme complex provides an efficient non-natural synthetic cascade route for fatty alcohol bioproduction alternative to complex de novo biosynthesis route.

Biomimetic scaffolds have been extensively studied for guiding osteogenesis through structural cues. Inspired by the natural bone growth process, we have employed a hierarchical outer-inner dual reinforcing strategy, which relies on the interfacial ionic bond interaction between amine/calcium and carboxyl groups, to build a nanofiber/particle dual strengthened hierarchical silk fibroin scaffold. This scaffold can provide an applicable form of osteogenic structural cue and mimic the natural bone forming process. Owing to the active interaction between compositions located in the outer pore space and the inner pore wall, the scaffold has over 4 times improvement in the mechanical properties, followed by a significant alteration of the cell-scaffold interaction pattern, demonstrated by over 2 times elevation in the spreading area and enhanced osteogenic activity potentially involving the activities of integrin, vinculin and Yes-associated protein (YAP). The in vivo performance of the scaffold identified the inherent osteogenic effect of the structural cue, which promotes rapid and uniform regeneration. Overall, the hierarchical scaffold is promising in promoting uniform bone regeneration through its specific structural cue endowed by its micro-nano construction.