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Forward and reverse primers.

Significantly different genes sarcomatoid vs. clear cell.

Phytophthora sojae infection severely impairs soybean production. We previously identified a dirigent protein, GmDRR1 (Glycine max Disease Resistant Response 1), that increases soybean resistance to P. sojae. However, the molecular basis of GmDRR1 function remained largely uncharacterized. In the present study, analysis of GmDRR1-RNAi, GmDRR1-overexpressing, and CRISPR/Cas9-derived Gmdrr1 mutant lines revealed that GmDRR1 expression significantly restricted P. sojae growth. Combining co-immunoprecipitation with liquid chromatography–tandem mass spectrometry revealed a GmDRR1-interacting protein, GmDRR2, which is homologous to GmDRR1. An E-coniferyl alcohol coupling assay indicated that GmDRR1 promotes the synthesis of (+)-pinoresinol, which helps to protect plants from P. sojae. The GmNAC1 (Glyma.05G025500) transcription factor bound to the GmDRR1 promoter both in vitro and in vivo to upregulate GmDRR1 expression. Soybean resistance to P. sojae was increased by overexpression of GmNAC1. Our findings suggest a novel signaling pathway involving a NAC transcription factor that mediates soybean resistance to P. sojae. Specifically, GmNAC1 directly induces GmDRR1 expression to increase resistance of soybean plants to P. sojae.

Six major QTLs for wheat grain size and weight were identified on chromosomes 4A, 4B, 5A and 6A across multiple environments, and were validated in different genetic backgrounds. Grain size and weight are crucial components of wheat yield. Dissection of their genetic control is thus essential for the improvement of yield potential in wheat breeding. We used a doubled haploid (DH) population to detect quantitative trait loci (QTLs) for grain width (GW), grain length (GL), and thousand grain weight (TGW) in five environments. Six major QTLs, QGw.cib-4B.2, QGl.cib-4A, QGl.cib-5A.1, QGl.cib-6A, QTgw.cib-4B, and QTgw.cib-5A, were consistently identified in at least three individual environments and in best linear unbiased prediction (BLUP) datasets, and explained 5.65–34.06% of phenotypic variation. QGw.cib-4B.2, QTgw.cib-4B, QGl.cib-5A.1 and QGl.cib-6A had no effect on grain number per spike (GNS). In addition to QGl.cib-4A, the other major QTLs were further validated by using Kompetitive Allele Specific PCR (KASP) markers in different genetic backgrounds. Moreover, significant interactions between the three major GL QTLs and two major TGW QTLs were observed. Comparison analysis showed that QGl.cib-5A.1 and QGl.cib-6A are likely new loci. Notably, QGw.cib-4B.2 and QTgw.cib-4B were co-located on chromosome 4B and improved TGW by increasing only GW, unlike nearby or overlapped loci reported previously. Three genes associated with grain development within the QGw.cib-4B.2/QTgw.cib-4B interval were identified by searches on sequence similarity, spatial expression patterns, and orthologs. The major QTLs and KASP markers reported here will be useful for elucidating the genetic architecture of grain size and weight and for developing new wheat cultivars with high and stable yield.

Two major and stable QTLs for spike compactness and length were detected and validated in multiple genetic backgrounds and environments, and their pleiotropic effects on yield-related traits were analyzed. Spike compactness (SC) and length (SL) are greatly associated with wheat (Triticum aestivum L.) grain yield. To detect quantitative trait loci (QTL) associated with SC and SL, two biparental populations derived from crosses of Chuanmai42/Kechengmai1 and Chuanmai42/Chuannong16 were employed to perform QTL mapping in five environments. A total of 34 QTLs were identified, in which six major QTLs were repeatedly detected in more than four environments and the best linear unbiased prediction datasets, explaining 7.13–33.6% of phenotypic variation. These major QTLs were co-located in two genomic regions on chromosome 5A and 6A, namely QSc/Sl.cib-5A and QSc/Sl.cib-6A, respectively. By developing kompetitive allele-specific PCR (KASP) markers that linked to them, the two loci were validated in different genetic backgrounds, and their interactions were also analyzed. Comparison analysis showed that QSc/Sl.cib-5A was not Vrn-A1 and Q, and QSc/Sl.cib-6A was likely a new locus for SC and SL. Both QSc/Sl.cib-5A and QSc/Sl.cib-6A had pleiotropic effects on other yield-related traits including plant height, thousand grain weight and grain length. Therefore, the two loci combined with the developed KASP markers might be potentially applicable in wheat breeding. Furthermore, based on the spatiotemporal expression patterns, gene annotation, orthologous search and sequence differences, TraesCS5A01G301400 and TraesCS6A01G090300 were considered as potential candidates for QSc/Sl.cib-5A and QSc/Sl.cib-6A, respectively. These results provided valuable information for fine mapping and cloning of the two loci in the future.

Two new

Mohangic acids are a class of

Decisive role of reduced vrs1 transcript abundance in six-rowed spike of barley carrying vrs1.a4 was genetically proved and its potential causes were preliminarily analyzed. Six-rowed spike 1 (vrs1) is the major determinant of the six-rowed spike phenotype of barley (Hordeum vulgare L.). Alleles of Vrs1 have been extensively investigated. Allele vrs1.a4 in six-rowed barley is unique in that it has the same coding sequence as Vrs1.b4 in two-rowed barley. The determinant of row-type in vrs1.a4 carriers has not been experimentally identified. Here, we identified Vrs1.b4 in two-rowed accessions and vrs1.a4 in six-rowed accessions from the Qinghai–Tibet Plateau at high frequency. Genetic analyses revealed a single nuclear gene accounting for row-type alteration in these accessions. Physical mapping identified a 0.08-cM (~ 554-kb) target interval on chromosome 2H, wherein Vrs1 was the most likely candidate gene. Further analysis of Vrs1 expression in offspring of the mapping populations or different Vrs1.b4 and vrs1.a4 lines confirmed that downregulated expression of vrs1.a4 causes six-rowed spike. Regulatory sequence analysis found a single ‘TA’ dinucleotide deletion in vrs1.a4 carriers within a ‘TA’ tandem-repeat–enriched region ~ 1 kb upstream of the coding region. DNA methylation levels did not correspond to the expression difference and therefore did not affect Vrs1 expression. More evidence is needed to verify the causal link between the ‘TA’ deletion and the downregulated Vrs1 expression and hence the six-rowed spike phenotype.

A novel qualitative locus regulating the uppermost internode elongation of barley was identified and mapped on 6H, and the candidate gene mining was performed by employing various barley genomic resources. The stem of grass crops, such as barley and wheat, is composed of several interconnected internodes. The extent of elongation of these internodes determines stem height, and hence lodging, canopy architecture, and grain yield. The uppermost internode (UI) is the last internode to elongate. Its elongation contributes largely to stem height and facilitates spike exsertion, which is crucial for final grain yield. Despite the molecular mechanism underlying regulation of UI elongation was extensively investigated in rice, little is known in barley. In this study, we characterized a barley spontaneous mutant, Sheathed Spike 1 (SS1), showing significantly shortened UI and sheathed spike (SS). The extension of UI parenchyma cell in SS1 was significantly suppressed. Exogenous hormone treatments and RNA-seq analysis indicated that the suppression of UI elongation is possibly related to insufficient content of endogenous bioactive gibberellin. Genetic analysis showed that SS1 is possibly controlled by a qualitative dominant nuclear factor. Bulked segregant analysis and further molecular marker mapping identified a novel major locus, HvSS1, in a recombination cold spot expanding 173.44-396.33 Mb on chromosome 6H. The candidate gene mining was further conducted by analyzing sequence differences, spatiotemporal expression patterns, and variant distributions of genes in the candidate interval by employing various barley genomic resources of worldwide collections of barley accessions. This study made insight into genetic control of UI elongation in barley and laid a solid foundation for further gene cloning and functional characterization. The results obtained here also provided valuable information for similar research in wheat.

Chronic cerebral hypoperfusion (CCH) is a clinical syndrome. Long-term chronic cerebral low perfusion will lead to insufficient blood supply to the brain, this leads to a pathological cascade. Salvianolic acid A (SAA) is a water-soluble phenolic acid contained in Salvia miltiorrhiza Bge., which has regulated effect on cardiovascular and cerebrovascular diseases. We established a chronic bilateral common carotid artery occlusion (BCCAO) model to investigate the improvement of SAA on cognitive dysfunction after chronic cerebral ischemia, and further explore whether it has a protective effect on hippocampal neuron damage. The mRNA changes of BCCAO model rats before and after SAA administration were analyzed based on RNA-Seq technique. Combined with GO and KEGG analysis results, PPI network analysis was performed for the major differential genes. Finally, the results were verified by western blot and enzyme-linked immunosorbent assay. After SAA treatment in BCCAO rats, behavioral experiments showed that SAA could improve learning and memory dysfunction caused by BCCAO model in rats. Moreover, it can significantly improve the hippocampal damage caused by long-term cerebral ischemia. Differential gene analysis revealed that there were multiple gene and pathway changes before and after SAA treatment. The genes we screened included TLR4, MyD88, Fos, Jun, ERK1/2, JNK and P38. Western blotting and enzyme-linked immunosorbent assay showed that SAA could regulate the TLR4/MAPKS/AP-1 signaling pathway, reduce the release of inflammatory factors, improve the nerve injury caused by brain ischemia in rats, and playing neuroprotective effects.

Social support are positively and causally related to mental health. Higher levels of perceived social support and group memberships are shown to be associated with lower depression symptomatology and recovery from depression, but the molecular biological mechanism behind its remains largely unknown. Here, we report that accompanying with companion ameliorated chronic unpredictable mild stress (CUMS) induced depression-like behaviors in mice. Accompanying with companion altered RNA expression profiles of nucleus accumbens (NAc) in CUMS-induced susceptible and resilience mice. 117 differentially expressed genes (DEGs) were found to be associated with depression-like behaviors, 17 DEGs associated with resilient behaviors, 43 DEGs associated with accompanying with companion. Importantly, 234 differentially expressed miRNAs that associated with accompanying with companion were obtained, and the miRNA-mRNA network associated with companion was established in NAc, based on the miRNA and mRNA profiles. Taken together, our findings revealed a potential new approach to improve depression-like behaviors, as well as many potential drug targets for the prevention or treatment of depression.

Metabolic changes have been recognized as an important hallmark of cancer cells. Cancer cells can promote their own growth and proliferation through metabolic reprogramming. Particularly, serine metabolism has frequently been reported to be dysregulated in tumor cells. 3-Phosphoglycerate dehydrogenase (PHGDH) catalyzes the first step in the serine biosynthesis pathway and acts as a rate-limiting enzyme involved in metabolic reprogramming. PHGDH upregulation has been observed in many tumor types, and inhibition of PHGDH expression has been reported to inhibit the proliferation of PHGDH-overexpressing tumor cells, indicating that it may be utilized as a target for cancer treatment. Recently identified inhibitors targeting PHGDH have already shown effectiveness. A further in-depth analysis and concomitant development of PHGDH inhibitors will be of great value for the treatment of cancer. In this review we describe in detail the role of PHGDH in various cancers and inhibitors that have recently been identified to highlight progression in cancer treatment. We also discuss the development of new drugs and treatment modalities based on PHGDH targets. Overexpression of PHGDH has been observed in melanoma, breast cancer, nasopharyngeal carcinoma, parathyroid adenoma, glioma, cervical cancer and others. PHGDH may serve as a molecular biomarker for the diagnosis, prognosis and treatment of these cancers. The design and development of novel PHGDH inhibitors may have broad implications for cancer treatment. Therapeutic strategies of PHGDH inhibitors in combination with traditional chemotherapeutic drugs may provide new perspectives for precision medicine and effective personalized treatment for cancer patients.

A novel seco-pregnane steroid bearing an oxygen-bridged structure and two new sesquiterpene lactones—namely, sausinone (1),14-oxidized mokko lactone (2), and (1R, 5R, 6R, 7R, 8S, 11S)-11,13-dihydrodehydrocostuslactone-8-O-6′-2″ (Z)-butenoyl-β-D-glucopy-ranoside (3)—along with 12 known compounds (4–15) were isolated from Saussurea involucrata. Notably, compounds 12–15 were isolated from this plant for the first time. Their structures were mainly established by one- and two-dimensional nuclear magnetic resonance analysis.

Collision avoidance path planning is still one of the essential problems in the design and application of an intelligent maritime navigation system. Its main obstacle is how to determine effective and cooperative collision avoidance maneuvers within a multi-ship encounter situation. By deconstructing a multi-ship encounter, this study adopted ship domain around target ships to assess the collision danger that own ship should avoid. Subsequently, the fitness function that has multiple dynamic obstacle constraints was designed in a two-dimensional map. Based on DE algorithm, a path-planning method was developed to compute collision-free and optimal navigation paths for ships. Simulation results show that the algorithm can generate a safe and suitable path from each perspective in a multi-ship encounter. The results also validate the practicality of the generated paths, consistency of the algorithm outputs and performance of the algorithm. It would be expected to provide a reference for collision avoidance decision making as well as contribute to the development of autonomous navigation systems.

Chemical investigation of secondary metabolites of the deep-sea-derived Alcanivorax sp. SHA4 identified a new compound 1 which was antimycic acid (2)'s acetyl derivative, and 11 known compounds (2-12). Their structures were elucidated by extensive nuclear magnetic resonance and mass spectrometry spectroscopic analyses, and the absolute configuration of compound 1 was determined by Marfey's method. Bioactivity assays indicated that compounds 1 and 2 exhibited significant neuroprotective properties against glutamate-induced PC12 cell death in 0.02-0.31 μM.

Phytochemical investigation on the ethanol extract of green walnut husks (Juglans mandshurica Maxim.) led to the isolation of two previously unknown compounds, including a macrolide compound (13S)-8-oxo-(9E, 11E)-8-oxo-octadeca-9,11-dien-13-olide (1) and a diarylheptanoid compound 1-(3'-methoxy-4'-hydroxyphenyl)-7-(3″,4″-dimethoxyphenyl)heptan-3-one (2), together with 19 known compounds. The structures of these 21 compounds were elucidated by extensive analyses of NMR and HR-MS data, and the basis of spectroscopic analysis.

Social support are positively and causally related to mental health. Higher levels of perceived social support and group memberships are shown to be associated with lower depression symptomatology and recovery from depression, but the molecular biological mechanism behind it s remains largely unknown. Here, we report that accompanying with companion ameliorated CUMS-induced depression-like behaviors in mice. Accompanying with companion altered RNA expression profiles of nucleus accumbens (NAc) in CUMS-induced susceptible and resilience mice. 117 differentially expressed genes (DEGs) were found to be associated with depression-like behaviors, 17 DEGs associated with resilient behaviors, 43 DEGs associated with accompanying with companion. Importantly, 234 differentially expressed miRNAs that associated with accompanying with companion were obtained, and the miRNA-mRNA network associated with companion was established in NAc, based on the miRNA and mRNA profiles. Taken together, our findings revealed a potential new approach to improve depression-like behaviors, as well as many potential drug targets for the prevention or treatment of depression.

Summary Background: To date, the ideal endoscopic knife for peroral endoscopic myotomy (POEM) with good performance and cost-effectiveness is still under investigation. The present study was aimed to evaluate the efficacy, safety, and cost-effectiveness of snare-assisted POEM, compared with the conventional endoscopic knife approach. Methods: From May 2017 to December 2018, patients with achalasia presenting for POEM without previous endoscopic or surgical therapy were prospectively recruited in this randomized controlled trial. Patients were randomly allocated to receive POEM using either the snare (snare group) or HookKnife (conventional group). The primary outcome was clinical success (Eckardt score ≤ 3) at 12-month follow-up, powered for noninferiority with a margin of −15%. The secondary outcomes included adverse events (AEs), procedure-related parameters, clinical outcomes, and cost-effectiveness. Results: A total of 75 patients with similar baseline characteristics between the snare (N = 37) and conventional (N = 38) groups were included. Clinical success at 12-month follow-up was achieved in 94.6% of patients in the snare group and 92.1% of patients in the conventional group (difference, 2.5% [95% CI, −8.7% to 13.7%]; P

Phytochemical investigation on the concentrate of Huangjing wine, resulted in the isolation of three new tyrosol derivatives 4′′′-hydroxyphenethyl 2-(R)-hydroxy-3-phenylpropionate (1), 4′′′-hydroxyphenethyl(4′-hydroxy-3′-methoxyphenyl)propionate (2) and 4′′-hydroxyphenethyl ethyl succinate (3), together with 5 known compounds, ferulic acid (4), L-phenyllactic acid (5), hydroxytyrosol (6), dihydroferulic acid (7), cyclo(L-Pro-D-Tyr) (8). Their structures were elucidated using spectroscopic analysis and by comparison with the literature data. All compounds displayed antioxidant effect in the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical. Among them, the new compound 2 exhibited obvious antioxidant effect, and new compounds 1 and 3 exhibited medium antioxidant effect.

The quality control of Saussurea involucrata has been greatly improved by macroscopic and microscopic identification and chemical profiling described in Chinese Pharmacopoeia since 2005. However, these methods have their own limitations, e.g., their dependence on personal experience and expertise, and it is a huge challenge to identify closely related species that share similar or identical morphological characteristics and chemical profiles. A novel and generally accepted identification strategy is urgently needed as a complement to regulations for protecting the public health interests. In this work, a comprehensive chromatographic fingerprint method was developed and tested on 43 samples from four haplotypes of S. involucrata according to DNA barcoding. Three common patterns consisting of 20, 14, and 7 common peaks were generated by frequency filters of median, upper quartile, and 100%, respectively. Based on two formerly screened patterns, S. involucrata can be effectively identified from its five easily confused snow lotus species, including the most closely related plant (S. orgaadayi) in the orthogonal partial least-squares discriminant analysis (OPLS-DA) models. The model is supported by good R and Q coefficients. In addition, different haplotypes of S. involucrata can be discriminated in the OPLS-DA model using the 20 common peaks. Among them, peaks 9, 11, 16 (zaluzanin C), and 18 (dehydrocostus lactone) have been identified as fingerprint markers of S. involucrata via S-plots and VIP values (>1). Additionally, peaks 19 and 20 were identified as linolenic acid and linoleic acid with anti-inflammatory activity, and they were isolated from the herb for the first time. Collectively, the chromatographic fingerprint of S. involucrata can be an effective and integrated method for the identification of authentic herbs from adulterant species or related plants, and discrimination of its different haplotypes provides an objective and reliable tool for quality control.

Objective Chronic subdural hematoma (CSDH) is a common neurosurgical condition with an increasing incidence and favorable prognosis. Surgery is the standard treatment for CSDH, and bur hole evacuation is the most widely employed technique. However, if mixed computed tomography (CT) density is found, burr hole hematoma evacuation is prone to recurrence. Endoscopic examination of the hematoma cavity provides a novel strategy. Here, we present a modification of burr hole evacuation by using neuroendoscopy through a novel small trapezoid bone flap and assess the advantages and risks of the procedure. Methods Twenty-five patients diagnosed with CSDH of mixed CT density were included in this study. Radiographic, epidemiologic, and clinical data were collected and analyzed. In all procedures the burr hole was replaced by a small trapezoidal cross-sectional bone flap, ∼2 cm in diameter. Neuroendoscopy was employed after the subdural cavity was cleaned and drained. The CSDH cavity was inspected thoroughly. If a blood clot, septa, stretching of cortical vessels, or intraluminal trabecular structures with active bleeding were found, the surgeon aspirated the region with a syringe pipe and/or used bipolar electrocoagulation. Results All 25 patients who received 26 neuroendoscopy-assisted operations achieved favorable clinical outcomes. The recurrence rate was 4%. The average operation time was slightly increased compared with the traditional burr hole evacuation due to the use of the neuroendoscope and eventual subsequent treatment. Conclusion Neuroendoscopy provides excellent illumination and vision when a small bone flap is employed. The main advantages of this technique include the precise treatment of structures which are related with progression and recurrence of CSDH, and the minimally invasive nature of the procedure.

Four new 4-alkyl-dihydroxyfuran coumarins, Mesuaferols D–F and iso-Mesuaferol F (1–4) were isolated from the flowering buds of Mesua ferrea. The chemical structures of these compounds were confirmed by the extensive analyses of NMR, UV, IR and HR-ESI-MS methods, the absolute configurations were established on the basis of the Mosher’s method, electron circular dichroism (ECD) measurement and theoretical calculation methods. The inhibitory activities of the isolates were evaluated on MDA-MB-231, MCF-7 and HepG2 cancer cell lines. All compounds exhibited potent activity against MCF-7 with IC50 as 26.68 μM, 37.75 μM, 20.53 μM and 33.43 μM respectively, while almost all compounds showed moderate cytotoxic activities against MDA-MB-231 and HepG2 cell lines. The results of prediction potential targets and molecule docking revealed that Mesuaferol D showed the most binding potential against mTOR.

Three new flavonoid glycosides, embeliaflavosides A-C (1–3), together with eight known flavonoid glycosides (4–11), were isolated from the fruits of Embelia ribes. Their structures were established...

Severe or prolonged stress increases the risk for developing psychopathological disorders. An individual's perception of stress exposure varies greatly, as do its consequences. Numerous individuals demonstrate resilience to psychological stress. The mRNA and microRNA profiles of stress susceptibility and resilience to induced psychological stress in the amygdala remain to be elucidated. In this work, psychological stress was induced in an observer mouse by witnessing a similar individual under attack by an aggressor. After 5 days of psychological stress, the degree of fear memory and anxiety in mice was measured by a social interaction test and elevated plus-maze (EPM) test. mRNA and microRNA profiles were quantified by high-throughput sequencing in amygdala tissue harvested from Control, Susceptible and Resilient mice. In the amygdala of Susceptible versus Resilient mice, the upregulation of peptide, thyrotropin-releasing hormone, ECM receptors, glutamatergic synapse, cytokine-cytokine receptor interaction, long-term depression, PI3K-Akt, oxytocin, GnRH, HIF-1, estrogen, and calcium signaling pathways may be related to psychological stress-induced susceptibility, and their downregulation may be related to resilience. The downregulation of adrenergic synapse, adherens junction, Wnt, sphingolipid, B cell receptor, cAMP, Rap1, and Toll-like receptor signaling pathways may be related to psychological stress-induced susceptibility, and the upregulation may be related to resilience. Results by sequencing of mRNA and microRNA profiles are consistent, in which some are validated by qRT-PCR and dual-luciferase reporter assay. Susceptibility and resilience induced by psychological stresses are caused by the imbalanced regulation of different synapses and signaling pathways in the amygdala.

Major depression is a prevalent affective disorder characterized by recurrent low mood. It presumably results from stress-induced deteriorations of molecular networks and synaptic functions in brain reward circuits of genetically-susceptible individuals through epigenetic processes. Epigenetic regulator microRNA-15b inhibits neuronal progenitor proliferation and is up-regulated in the medial prefrontal cortex of mice that demonstrate depression-like behavior, indicating the contribution of microRNA-15 to major depression. Using a mouse model of major depression induced by chronic unpredictable mild stress (CUMS), here we examined the effects of microRNA-15b on synapses and synaptic proteins in the nucleus accumbens of these mice. The application of a microRNA-15b antagomir into the nucleus accumbens significantly reduced the incidence of CUMS-induced depression and reversed the attenuations of excitatory synapse and syntaxin-binding protein 3 (STXBP3A)/vesicle-associated protein 1 (VAMP1) expression. In contrast, the injection of a microRNA-15b analog into the nucleus accumbens induced depression-like behavior as well as attenuated excitatory synapses and STXBP3A/VAMP1 expression similar to the down-regulation of these processes induced by the CUMS. We conclude that microRNA-15b-5p may play a critical role in chronic stress-induced depression by decreasing synaptic proteins, innervations, and activities in the nucleus accumbens. We propose that the treatment of anti-microRNA-15b-5p may convert stress-induced depression into resilience.

We report an electro-wetting liquid lens with dual apertures which consists of internal channel with two variable interfaces and external channel with a plano-concave solid lens. And we use LC cell and Polarizers to achieve switching between internal and external channel. The proposed lens can achieve a large turning range of focal length, and the shortest positive and negative focal length are ~24 mm and ~−16 mm, respectively. Meanwhile, the experimental results show that the angular resolution of the proposed lens can reach to $\sim 29^{\prime \prime }$ . It has potential to be applied in cameras, microscopes and so on.

Furfural from biomass such as corncob is an important chemical with wide applications. The current industrial production of furfural uses H2SO4 as catalyst which is highly toxic and corrosive. It was demonstrated that the acidic salt KHSO4 was an effective and safer catalyst for furfural production. The optimum conditions for furfural production from corncob were investigated. The XRD and TG analyses of raw corncob and typical reaction residue were conducted and discussed. Finally, an outlook to the future work was put forward.

Phenylpropionic acids are commonly used in the synthesis of pharmaceuticals, cosmetics, and fine chemicals. However, the synthesis of phenylpropionic acids faces the challenges of high cost of substrates and a limited range of products. Here, we present an artificially designed amino-group-transformation biocatalytic process, which uses simple phenols, pyruvate, and ammonia to synthesize diverse phenylpropionic acids. This biocatalytic cascade comprises an amino-group-introduction module and three amino-group-transformation modules, and operates in a modular assembly manner. Escherichia coli catalysts coexpressing enzymes from different modules achieve whole-cell simultaneous one-pot transformations of phenols into the corresponding phenylpropionic acids including (S)-α-amino acids, α-keto acids, (R)-α-amino acids, and (R)-β-amino acids. With cofactor recycling, protein engineering, and transformation optimization, four (S)-α-amino acids, four α-keto acids, four (R)-α-amino acids, and four (R)-β-amino acids are synthesized with good conversion (68-99%) and high enantioselectivities (>98%). Therefore, the amino-group-transformation concept provides a universal and efficient tool for synthesizing diverse products.

Anxiety is presumably driven by fear memory. The nucleus accumbens involves emotional regulation. Molecular profiles in the nucleus accumbens related to stress-induced fear memory remain elucidated. Fear memory in mice was induced by a paradigm of social defeat. Physical and psychological stress was delivered to an intruder that was attacked by an aggressive resident. Meanwhile, an observer experienced psychological stress by seeing aggressor attacks. The nucleus accumbens tissues from intruder and observer mice that appear fear memory and anxiety as well as control mice were harvested for analyses of mRNA and miRNA profiles by high throughput sequencing. In the nucleus accumbens of intruders and observers with fear memory and anxiety, genes encoding AdrRα, AChRM2/3, GluRM2/8, HrR1, SSR, BDNF and AC are upregulated, while genes encoding DR3/5, PR2, GPγ8 and P450 are downregulated. Physical and/or psychological stress leads to fear memory and anxiety likely by molecules relevant to certain synapses. Moreover, there are differential expressions in genes that encode GABARA, 5-HTR1/5, CREB3, AChRM2, RyR, Wnt and GPγ13 in the nucleus accumbens from intruders versus observers. GABAergic, serotonergic and cholinergic synapses as well as calcium, Wnt and CREB signaling molecules may be involved in fear memory differently induced by psychological stress and physical/psychological stress. The data from analyzing mRNA and miRNA profiles are consistent. Some molecules are validated by qRT-PCR and dual luciferase reporter assay. Fear memory and anxiety induced by the mixture of physical and psychological stress or psychological stress appear influenced by complicated molecular mechanisms in the nucleus accumbens.

Pyroptosis is a form of inflammatory cell death that could be driven by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation following myocardial infarction (MI). Emerging evidence suggests the therapeutic potential for ameliorating MI-induced myocardial damages by targeting NLRP3 and pyroptosis. In this study, we investigated the myocardial protection effect of a novel anthraquinone compound (4,5-dihydroxy-7-methyl-9,10-anthraquinone-2-ethyl succinate) named Kanglexin (KLX) in vivo and in vitro. Male C57BL/6 mice were pre-treated either with KLX (20, 40 mg· kg−1per day, intragastric gavage) or vehicle for 7 consecutive days prior to ligation of coronary artery to induce permanent MI. KLX administration dose-dependently reduced myocardial infarct size and lactate dehydrogenase release and improved cardiac function as compared to vehicle-treated mice 24 h after MI. We found that MI triggered NLRP3 inflammasome activation leading to conversion of interleukin-1β (IL-1β) and IL-18 into their active mature forms in the heart, which could expand the infarct size and drive cardiac dysfunction. We also showed that MI induced pyroptosis, as evidenced by increased DNA fragmentation, mitochondrial swelling, and cell membrane rupture, as well as increased levels of pyroptosis-related proteins, including gasdermin D, N-terminal GSDMD, and cleaved caspase-1. All these detrimental alterations were prevented by KLX. In hypoxia- or lipopolysaccharide (LPS)-treated neonatal mouse ventricular cardiomyocytes, we showed that KLX (10 μM) decreased the elevated levels of terminal deoxynucleotidyl transferase dUTP nick end labeling- and propidium iodide-positive cells, and pyroptosis-related proteins. We conclude that KLX prevents MI-induced cardiac damages and cardiac dysfunction at least partly through attenuating NLRP3 and subsequent cardiomyocyte pyroptosis, and it is worthy of more rigorous investigations for its potential for alleviating ischemic heart disease.

Buffaloes, as highly susceptible definitive hosts of Fasciola gigantica, suffer from a high infection rate of fasciolosis, which causes enormous economic losses. Repeat infection is responsible for this high rate; thus, elucidating the protective immunity mechanism in repeat infection is decisive in fasciolosis prevention. Herein, a secondary experimental infection model was established to preliminarily reveal the protective immunity that occurs in repeat infection. In brief, animals were assigned to three groups: group A (uninfected control), group B (primary infection) and group C (secondary infection). Buffaloes were autopsied 20 weeks post-infection for measurements of the recovered flukes and hepatic examination. In addition, the detection of specific antibody (IgG) responses to F. gigantica excretory-secretory product (FgESP) throughout the whole period and weight gain throughout the first 4 months as a percentage (%) of the starting weight were also determined. The serum hepatic enzyme gamma glutathione transferase (GGT) levels were monitored to assess hepatic damage throughout the study period. Infection establishment was compared between group B and group C. Similar specific IgG patterns were observed between group B and group C, and hepatic damage was more severe in group C than group B. Significant differences in weight gain as a percentage of the start weight were observed between group A and group B at the 3rd and 4th months postprimary infection, while significant differences were not observed between group A and group C or group B and group C. Our results suggest that challenge infection cannot induce resistance against F. gigantica in buffaloes, which is consistent with the protective immunity against Fasciola hepatica reinfection observed in sheep and goats.

Atorvastatin ester (Ate) is a structural trim of atorvastatin that can regulate hyperlipidemia. The purpose of this study was to evaluate the lipid-lowering effect of Ate. Male Sprague Dawley (SD) rats were fed a high-fat diet for seven months and used as a hyperlipidemia model. The lipid level and liver function of the hyperlipidemia rats were studied by the levels of TG, TC, LDL, HDL, ALT, and AST in serum after intragastric administration with different doses of Ate. HE staining was used to observe the pathological changes of the rat liver and gastrocnemius muscle. The lipid deposits in the liver of rats were observed by staining with ORO. The genes in the rat liver were sequenced by RNA-sequencing. The results of the RNA-sequencing were further examined by qRT-PCR and western blotting. Biochemical test results indicated that Ate could obviously improve the metabolic disorder and reduce both the ALT and AST levels in serum of the hyperlipidemia rats. Pathological results showed that Ate could improve HFD-induced lipid deposition and had no muscle toxicity. The RNA-sequencing results suggested that Ate affected liver lipid metabolism and cholesterol, metabolism in the hyperlipidemia-model rats may vary via the PPAR-signaling pathway. The western blotting and qRT-PCR results demonstrated the Ate-regulated lipid metabolism in the hyperlipidemia model through the PPAR-signaling pathway and HMGCR expression. In brief, Ate can significantly regulate the blood lipid level of the model rats, which may be achieved by regulating the PPAR-signaling pathway and HMGCR gene expression.

Ethnopharmacological relevance Tongmai granules (TMG) is composed of Salvia miltiorrhiza Bge., Radix puerariae Lobata., and Ligusticum chuanxiong hort. TMG is mainly used for ischemic cardiovascular, cerebrovascular diseases, atherosclerosis, coronary heart disease, cerebral infarction and cerebral ischemia. TMG is a kind of traditional compound granule, which has a protective effect on brain injury. However, the potential protective mechanism of the TMG has not been elucidated. Aim of the study TMG has a good effect on brain injury, but its brain protective mechanism is still unclear. The purpose of this study was to confirm the neuroprotective mechanism of TMG, reveal its target genes and identify the active components of TMG. Materials and methods High-performance liquid chromatography (HPLC) was used to identify the fingerprint of TMG. UPLC-Q-TOF-MSE was used to analyze the base peak intensity (BPI) chromatograms of TMG. TMG was pre-administered for one week, brain injury and edema were induced by injection of glutamate (Glu) into the lateral ventricles of rats. HE staining was used to investigate the pathological damage caused by Glu in the hippocampus of rats, and the RNA-seq was used to analyze the changes of different genes before and after TMG treatment. Finally, changes of related proteins were analyzed by qRT-PCR, Western blot, and other molecular biological methods. Dosage of TMG were set to 0.6 g/kg, 1.2 g/kg and 2.4 g/kg. Results We found that TMG contained many active components, including salvianolic acid, puerarin, ferulic acid, etc. TMG could improve cerebral edema and brain injury induced by Glu. After TMG treatment, differential gene analysis showed that differential genes were significantly enriched in toll-like receptor signaling pathway. qRT-PCR validation results were consistent with RNA-Seq analysis results. Combined with Western blot analysis, we found that TMG ultimately regulated the expression of inflammatory cytokines by affecting the TLR4/MyD88/AP-1 pathway. Conclusions In this study, we combined TMG with RNA-seq analysis to demonstrate that TMG may play a neuroprotective role by regulating Toll-like receptor signaling pathway and down-regulating the expression of inflammatory cytokine. TMG may become a kind of traditional Chinese medicine with neuroprotective potential.

Three new flavonoid glycosides, embeliaflavosides A-C (

This paper proposes to improve the form accuracy of a machined surface produced by an ordinary milling machine by diamond fly cutting using controlled cutting with reference surface (CCRS), an in-process measurement and control method. CCRS improves machined surface accuracy by controlling the relative displacement between the tool and workpiece. Diamond fly cutting using CCRS was demonstrated to reduce the table motion error on an ordinary milling machine.

In this paper, we propose and experimentally demonstrate a tunable liquid lens integrated with an aspherical surface for spherical aberration and distortion compensation. Through optimizing the aspherical surface’s morphology, the spherical aberration and distortion can be significantly reduced. The root mean square spot size at focus is distinctly reduced from 55. 7 μ m to 2. 095 μ m after performing optimum optimization. The tunable liquid lens is integrated with the aspheric surface with 6 mm clear aperture and 19.2 mm minimum focal length and demonstrate the improvement in optical performance over the conventional lens without an aspheric surface over a focal length range. Its applications in microscope system and tunable-focus eyeglasses are foreseeable.

Early postoperative rehabilitation training for supracondylar fracture of femur aids in accelerating healing with shorter recovery periods. Presently, clinical studies on early postoperative weight training are still in the nascent stage. The weight-bearing capacity at different healing stages typically depends on clinical experience, and there is a lack of standards to quantify the weight that is conducive to healing of fractures. In this paper, a three-dimensional (3D) geometric model of the femur is obtained using imaging data, a locking plate fixation model of a simple supracondylar fracture of the femur, considering the angle and spatial direction of the fracture surface, is established, the stress distribution and load transmission mechanism of the fracture fixation model in a single-leg standing posture are studied, and the weight-bearing capacity of a standing single leg at the early stage of fracture is given. This provides the basis for objective quantification of early postoperative weight-bearing capacity.

Major depressive disorder characterized as recurrent negative mood is one of the prevalent psychiatric diseases. Chronic stress plus lack of reward may induce long-term imbalance between reward and penalty circuits in the brain, leading to persistent negative mood. Numerous individuals demonstrate resilience to chronic mild stress. Molecular mechanisms for major depression and resilience in the brain remain unclear. After juvenile mice were treated by the chronic unpredictable mild stress (CUMS) for 4 weeks, they were screened by sucrose preference, Y-maze and forced swimming tests to examine whether their behaviors were depression-like or not. mRNA and miRNA profiles were quantified by high-throughput sequencing in amygdala tissues harvested from control, CUMS-susceptible, and CUMS-resilience mice. 1.5-fold ratio in reads per kilo-base per million reads was set to be the threshold to judge the involvement of mRNAs and miRNAs in the CUMS, major depression, or resilience. In the amygdala from CUMS-susceptible mice, the expression of genes relevant to GABAergic, cholinergic, glutamatergic, dopaminergic, and serotonergic synapses was changed, as well as the expression of genes that encoded signal pathways of PI3K-Akt, calcium, cAMP, MAPK, and drug addiction was imbalanced. The expression of these genes in the amygdala form CUMS-resilience mice was less changed. The downregulation of genes relevant to synaptic functions and the imbalance of intra-signaling pathway in the amygdala are associated with major depression. Consistent results through sequencing mRNA and miRNA and using different methods validate our finding and conclusion.

As a part of our ongoing search for bioactive compounds from the dried latex of Euphorbia resinifera (Euphorbium), a new rearranged tirucallane triterpene with a spiro [5,6] ring system, euphorol K (1), and a novel euphane triterpene hydroperoxide, euphorol J (2), together with a known compound, kansuinone (3) have been isolated. Their structures were established on the basis of extensive analyses of their spectroscopic, circular dichroism (CD) measurement and theoretical calculation (ECD) methods. The cytotoxicity of all compounds against MCF-7, U937 and C6 cancer cell lines was evaluated. Compounds 1−3 exhibited various degrees of cytotoxic effect against MCF-7.

Two new ingol-type diterpenes, euphoresins A–B (1–2), have been isolated from the methanol extract of Euphorbium, the latex of Euphorbia resinifera Berg. Their structures were established o...

Optical axial scanning is essential process to obtain 3D information of biological specimens. To realize optical axial scanning without moving, the tunable lens is a solution. However, the conventional tunable lenses usually induce non-uniform magnification and resolution issues. In this paper, we report a movable electrowetting optofluidic lens. Unlike the conventional tunable lens, our proposed optofluidic lens has two liquid-liquid (L-L) interfaces, which can move in the cell by an external voltage. The object distance and image distance are adjusted by shifting the L-L interface position. Therefore, the proposed lens can realize optical axial scanning with uniform magnification and resolution in microscopy. To prove the concept, we fabricate an optofluidic lens and use it in optical axial scanning. The scanning distance is more than 1 mm with uniform magnification and good imaging quality. Widespread application of such a new adaptive zoom lens is foreseeable.

Anisodamine (654-1), a well-known cholinergic antagonist, is marketed as synthetic anisodamine (mixture of four isomers, 654-2) in China. To preparative resolution and comparison of the bioactivities of the four isomers of synthetic anisodamine, current work explores an economic and effective separation method by using preparative high performance liquid chromatography (HPLC) and diastereomer crystallization. Their absolute configurations were established by single-crystal X-ray diffraction and circular dichroism method. The purities of each isomer were more than 95%. Among them, 654-2-A2 (6R, 2'S configuration) exhibited better effect on cabachol preconditioned small intestine tension more than 654-2 and other isomers. The direct separation method without using HPLC was tried as well, which was still on progress. This is the first report of the method for preparative separation of four isomers of synthetic anisodamine which could be used for large-scale production in industry.

In this paper, we report a prism with two liquid–liquid interfaces based on electrowetting effect. The prism is filled with two immiscible liquids which form two liquid–liquid interfaces. In the device, the filling liquids from the top to the bottom are conductive liquid, oil and conductive liquid. The shape of the two liquid–liquid interfaces will be changed when different voltages are applied to the opposite sidewalls. Our device is capable of wide-angle beam steering and the function of light beam translational. Our results show that the light beam can be deflected by ∼ 22 . 3 ° ( − 11 . 5 ° to + 10 . 8 ° ) and the translational distance is 3.1 mm (−1.5 mm to +1.6 mm). The proposed prism has a wide application in light detection, telecommunications, light alignment and other industrial applications.

The root cause behind the development of chronic obstructive pulmonary disease (COPD) is cigarette smoke that induces the inflammation of the lung tissue and alveolar destruction. Long-term cigarette smoking can lead to deterioration in lung parenchymal function and cause structural changes in the lung, further resulting in pulmonary fibrosis. Rhodiola rosea L., a traditional medicinal perennial herb, is well known for its numerous pharmacological benefits, including anti-inflammation, antioxidant, antifatigue, antidepressive, and antifibrotic properties. Here, we evaluated the pharmacological effects and mechanisms of the Rhodiola rosea L. (RRL) macroporous resin extract on COPD caused by lipopolysaccharide (LPS) and cigarette smoke (CS) in rats. The RRL significantly improved the pathological structure of the lung tissue. Additionally, RRL decreased the infiltration of inflammatory cells and, subsequently, oxidative stress. Furthermore, the RNAseq assay indicated that RRL attenuated the CS and LPS-induced COPD via anti-inflammatory, antifibrotic, and antiapoptotic activities. Western blot analysis substantiated that the RRL resulted in upregulated levels of Nrf2 and HO-1 as well as downregulated levels of IκBα, NF-κB p65, α-SMA, and TGF-β1. Interestingly, the RRL could protect rats from CS and LPS-induced COPD by inhibiting the ERK1/2 and Smad3 signaling pathways and apoptosis. Thus, the RRL could attenuate CS and LPS-induced COPD through inflammation inhibition and antioxidant and antifibrosis pathways.

Decisive role of reduced vrs1 transcript abundance in six-rowed spike of barley carrying vrs1.a4 was genetically proved and its potential causes were preliminarily analyzed. Six-rowed spike 1 (vrs1) is the major determinant of the six-rowed spike phenotype of barley (Hordeum vulgare L.). Alleles of Vrs1 have been extensively investigated. Allele vrs1.a4 in six-rowed barley is unique in that it has the same coding sequence as Vrs1.b4 in two-rowed barley. The determinant of row-type in vrs1.a4 carriers has not been experimentally identified. Here, we identified Vrs1.b4 in two-rowed accessions and vrs1.a4 in six-rowed accessions from the Qinghai-Tibet Plateau at high frequency. Genetic analyses revealed a single nuclear gene accounting for row-type alteration in these accessions. Physical mapping identified a 0.08-cM (~ 554-kb) target interval on chromosome 2H, wherein Vrs1 was the most likely candidate gene. Further analysis of Vrs1 expression in offspring of the mapping populations or different Vrs1.b4 and vrs1.a4 lines confirmed that downregulated expression of vrs1.a4 causes six-rowed spike. Regulatory sequence analysis found a single 'TA' dinucleotide deletion in vrs1.a4 carriers within a 'TA' tandem-repeat-enriched region ~ 1 kb upstream of the coding region. DNA methylation levels did not correspond to the expression difference and therefore did not affect Vrs1 expression. More evidence is needed to verify the causal link between the 'TA' deletion and the downregulated Vrs1 expression and hence the six-rowed spike phenotype.

Traditional Chinese Medicine Qianghuo Shengshi decoction (QSD) is widely used in the treatment of nervous headache, rheumatoid arthritis, sciatica, allergic purpura, and other clinical diseases in China. However, the underlying mechanisms of its anti-inflammatory and analgesic effects has not been elucidated.The aim of this study was to confirm the anti-inflammatory and analgesic effects and the underlying mechanism of QSD in vivo. In addition, this study was also to isolate and analyze the main active components of QSD by high performance liquid chromatography (HPLC).In this study, the acetic acid writhing test, hot plate test and ear swelling test and formalin test were carried out to explore the anti-inflammatory and analgesic effects of QSD. The doses were set to 7.8 g/kg, 15.6 g/kg and 31.2 g/kg body weight. Western blot was utilized to study further possible mechanisms of QSD. Moreover, the HPLC method was used to isolate and identify the components in the extraction of QSD.Twelve characteristic peaks were recognized in the HPLC spectrum, which all were the known compounds. The QSD exhibited dose-dependent effects in anti-inflammatory and analgesic aspects. Compared with model group, the writhing times of in groups of different doses of QSD (15.6 g/kg and 31.2 g/kg (oral administration = p.o.)) were reduced by 33.0% and 45.8% and indicated the QSD showed significant (p 0.05) peripheral analgesic effect. QSD ((31.2 g/kg), p.o.) showed significant(p 0.05) analgesic effect in the hot plate test. Inhibition rates of QSD ((15.6 g/kg and 31.2 g/kg), p.o.) in ear swelling test induced by p-xylene were 27.5% and 54.6% and demonstrated the significant (p 0.05) anti-inflammatory activity. QSD ((31.2 g/kg), p.o.) significantly (p 0.05) reduced times of paw licking in formalin test, and its inhibition rates were 34.3% and 28.0% in Phase I and Phase Ⅱ response, respectively. Western blot results showed that QSD inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) protein and cAMP response element-binding protein (CREB).These results of this study undoubtedly confirmed that QSD expressed obvious analgesic and anti-inflammatory activities. Anti-inflammatory and analgesic effects of QSD may be achieved by regulating the MAPKs protein and further regulating the expression of CREB. In all, QSD may play an anti-inflammatory and analgesic role through a variety of active ingredients.

To improve the accuracy of the machined surface produced by an ordinary milling machine, a system called workpiece-referred form accuracy control (WORFAC) was developed and confirmed in diamond turning. However, non-rotational symmetric surface structures, such as V-grooves, pyramid structures, F-theta lenses, and other free form surface cannot be machined by diamond turning. We proposed to improve the form accuracy of a machined surface produced by an ordinary milling machine by diamond fly cutting using controlled cutting with reference surface (CCRS), an in-process measurement and control method. Fly cutting is usually used to manufacture ultra-precision microstructures with nanometric surface roughness and submicrometric form accuracy, without the need for subsequent polishing. Nevertheless, a high level of accuracy has only recently been achieved on ultra-precision milling machines. In this study, we verified the effectiveness of fly cutting with CCRS on an ordinary milling machine. CCRS improves machined surface accuracy by controlling the relative displacement between the tool and workpiece. Diamond fly cutting using CCRS was demonstrated to reduce the table motion error on an ordinary milling machine. The experiments of curved surface machining by uncontrolled machining and control machining were conducted, and the effectiveness of improving the circular are machining accuracy of the general-purpose milling machine was confirmed.

In this paper, we propose a real time, ultrahigh accuracy and full-field-of-view (RUF) algorithm for full field of view (FOV) imaging system. The proposed algorithm combines rough matching and precise matching method to stitch multiple images with the whole FOV in short time and high imaging quality. In order to verify real-time imaging effect of RUF algorithm, we also fabricate a multi-camera imaging system which includes 19 independent cameras. And the experiment result practically illustrates that full-FOV system can achieve good performances under a near-limiting FOV of 360° × 240° with low distortion, meanwhile, optical resolution reaches up to 95 megapixels. 100% registration-accuracy RUF algorithm for imaging in one second can be widely applied to any optical imaging engineering field with large FOV, such as remote sensing imaging, microscopy imaging, monitoring system engineering fields and so on.