Lower Cretaceous theropod tracks with the new ichnogenus and combination Lockleypus luanpingensis from the Dabeigou Formation of the Luanping Basin,Hebei Province,China

Theropod footprints from the Jingshang tracksite in the Lower Cretaceous Dabeigou Formation of the Luanping Basin, Hebei Province, China, are re-evaluated after new discoveries at this locality. They occur in a succession with sandstone, mudstone, and calcareous shale. The depositional environment was a shallow lake shore, comparable in age to the famous Jehol Biota. Based on the distinct morphology with peculiar features of the ratio of the outer digits, the footprints formerly assigned to Changpeipus carbonicus are now referred to the new ichnogenus and combination Lockleypus luanpingensis. The possible trackmaker was a relatively large ornithomimosaurian theropod thus far not known from the skeletal record of the Jehol Biota.     

Ramanome technology platform for label-free screening and sorting of microbial cell factories at single-cell resolution

Phenotypic profiling of natural, engineered or synthetic cells has increasingly become a bottleneck in the mining and engineering of cell factories. Single-cell phenotyping technologies are highly promising for tackling this hurdle, yet ideally they should allow non-invasive live-cell probing, be label-free, provide landscape-like phenotyping capability, distinguish complex functions, operate with high speed, sufficient throughput and low cost, and finally, couple with cell sorting so as to enable downstream omics analysis. This review focuses on recent progress in Ramanome Technology Platform (RTP), which consists of Raman spectroscopy based phenotyping, sorting and sequencing of single cells, and discuss the key challenges and emerging trends. In addition, we propose ramanome, a collection of single-cell Raman spectra (SCRS) acquired from individual cells within a cellular population or consortium, as a new type of biological phenome datatype at the single-cell resolution. By establishing the phenome-genome links in a label-free, single-cell manner, RTP should find wide applications in functional screening and strain development of live microbial, plant and animal cell factories.     

New derivatives of ursolic acid through the biotransformation by Bacillus megaterium CGMCC 1.1741 as inhibitors on nitric oxide production

Microbial transformation of ursolic acid (1) by Bacillus megaterium CGMCC 1.1741 was investigated and yielded five metabolites identified as 3-oxo-urs-12-en-28-oic acid (2); 1β,11α-dihydroxy-3-oxo-urs-12-en-28-oic acid (3); 1β-hydroxy-3-oxo-urs-12-en-28, 13-lactoe (4); 1β,3β, 11α-trihydroxyurs-12-en-28-oic acid (5) and 1β,11α-dihydroxy-3-oxo-urs-12-en-28-O-β-d-glucopyranoside (6). Metabolites 3, 4, 5 and 6 were new natural products. Their nitric oxide (NO) production inhibitory activity was assessed in lipopolysaccharide (LPS) – stimulated RAW 264.7 cells. Compounds 3 and 4 exhibited significant activities with the IC₅₀ values of 1.243 and 1.711 μM, respectively. A primary structure-activity relationship was also discussed.     

Ac4GlcNAcF3, an OGT-tolerated but OGA-resistant regulator for O-GlcNAcylation

O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational monosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes. The dynamic nature of O-GlcNAc has enabled researchers to modulate the stoichiometry of O-GlcNAc on proteins in order to investigate its function. Cell permeable small moleculars have proven invaluable tools to increase O-GlcNAc levels. Herein, using in vitro substrate screening, we identified GlcNAcF₃ as an OGT-accepted but OGA-resistant sugar mimic. Cellular experiments with cell-permeable peracetylated-GlcNAcF₃ (Ac₄GlcNAcF₃) displayed that Ac₄GlcNAcF₃ was a potent tool to increase O-GlcNAc levels in several cell lines. Further, NIH3T3 cells interfered with OGT (siOGT) showed significant decreasing of O-GlcNAc levels with Ac₄GlcNAcF₃ treatment, indicating O-GlcNAcF₃ was an OGT-dependent modification. In addition, cellular toxic assay confirmed O-GlcNAcF₃ production has no significant effect on cell proliferation or viability. Thus, Ac₄GlcNAcF₃ represents a safe and dual regulator for both OGT and OGA, which will benefit the study of O-GlcNAc.     

Genomic evidence for the population genetic differentiation of Misgurnus anguillicaudatus in the Yangtze River basin of China

Misgurnus anguillicaudatus, an important aquatic species, is mainly distributed in the Yangtze River basin. To reveal the population genetic structure of M. anguillicaudatus distributed in the Yangtze River basin, genotyping by sequencing (GBS) technique was employed to detect the genome wide genetic variations of M. anguillicaudatus. A total of 30.03 Gb raw data were yielded from 70 samples collected from 15 geographic sites located in the Yangtze River basin. Subsequently, 2092 high quality SNPs were genotyped across these samples and used for a series of genetic analysis. The results of genetic analysis showed that high levels of genetic diversity were observed and the populations from upper reaches (UR) were significantly differentiated from the middle and lower reaches (MLR) of Yangtze River basin. Meanwhile, no significant isolation by distance was detected among the populations. Ecological factors (e.g. complicated topography and climatic environment) and anthropogenic factors (e.g. aquaculture and agriculture cultivation) might account for the genetic disconnectivity between UR and MLR populations. This study provided valuable genetic data for the future breeding program and also for the conversation and scientific utilization of those abundant genetic resources stored in the Yangtze River basin.     

Design,synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H1 antagonize activities

To improve the anti-inflammatory activity of desloratadine, we designed and synthesized a series of novel desloratadine derivatives. All compounds were evaluated for their anti-inflammatory and H₁ antagonistic activities. Among them, compound 2c showed the strongest H₁ antagonistic and anti-inflammatory activity. It also exhibited promising pharmacokinetic profiles and low toxicity. All these results suggest that compound 2c as a novel anti-allergic agent is worthy of further investigation.     

Polybenzyls from Gastrodia elata,their agonistic effects on melatonin receptors and structure-activity relationships

Gastrodia elata is a famous traditional Chinese herb with medicinal and edible application. In this study, nine polybenzyls (1?9), including six new ones (2?5, 7 and 9), were isolated from the EtOAc extract of G. elata. Five compounds 1, 3, 4, 6 and 8 were found to activate melatonin receptors. Especially, compound 1 showed agonistic effects on MT₁ and MT₂ receptors with EC₅₀ values of 237 and 244 μM. For better understanding their structure-activity relationships (SARs), ten polybenzyl analogs were further synthesized and assayed for their activities on melatonin receptors. Preliminary SARs study suggested that two para-hydroxy groups were the key pharmacophore for maintaining activity. Molecular docking simulations verified that compound 1 could strongly interact with MT₂ receptor by bonding to Phe 118, Gly 121, His 208, Try 294 and Ala 297 residues.     

Bmo-miR-3377-5p down-regulates the Bombyx mori Sericin gene-1

MiRNAs are small non-coding molecules, which can regulate a huge number of genes. Based on bioinformatics analysis, we found a target site in the 3′UTR of BmSer-1 for binding bmo-miR-3377-5p. By using semi-quantitative RT-PCR, we detected that miR-3377-5p and BmSer-1 were both more highly expressed in the middle silk gland than in other tissues of 3-day-old fifth-instar Bombyx mori larvae, implying that there is a spatiotemporal condition for miR-3377-5p regulating on BmSer-1. To confirm this prediction, a BmSer-13′UTR recombinant luciferase reporter pGL3.0 [A3-luc-BmSer-1-3′UTR-SV40] and pri-bmo-miR-3377-5p expression pcDNA3.0 [ie1-egfp-pri-bmo-miR-3377-5p-SV40] were constructed and co-transfected into B. mori ovary cells (BmN cells). The results showed that miR-3377-5p suppressed the expression of BmSer-1 significantly (P < .001). When BmN cells were co-transfected by an artificial inhibitor together with a miR-3377-5p expression vector and a BmSer-1-3′UTR recombinant plasmid, BmSer-1 expression increased significantly (P < .05), indicating that the inhibitor was active against miR-3377-5p, and expression of BmSer-1 was recovered. Moreover, we injected miR-3377-5p expression plasmid and bmo-miR-3377-5p inhibitor into 3-day-old fifth-instar larvae. At 36 h post-injection, silk glands were collected for total RNA extraction. Quantitative RT-PCR analysis showed that miR-3377-5p down-regulated the expression of BmSer-1 in vivo, while there was no significant difference inhibitor treatment group compared with NC. Thus, we conclude that miR-3377-5p down-regulated the expression of BmSer-1. Our results provide insight for understanding the function of miRNAs and the regulation network of silk protein genes.     

Microbial production of sialic acid and sialylated human milk oligosaccharides: Advances and perspectives

Sialic acids (SAs) are important functional sugars, and monomers of sialylated human milk oligosaccharides (sialylated HMOs or sialyllactoses), which are crucial for improving infant development and can facilitate infant brain development, maintain brain health, and enhance immunity. The most common form of SA is N-acetylneuraminic acid (NeuAc), and the main forms of sialyllactoses are 6′-sialyllactose (6′-SL) and 3′-sialyllactose (3′-SL). As functional food additive, the demand for NeuAc and sialyllactoses will continuously increase due to their wide and important fields of application. However, NeuAc and sialyllactoses produced by traditional extraction methods are inefficient and may cause allergen contamination, and cannot keep up with the rapidly increasing market demand. Therefore, the production of NeuAc and sialyllactoses by sustainable biotechnological methods have attracted increasing attention. In particular, the development of metabolic engineering and synthetic biology techniques and strategies have promoted efficient biosynthesis of NeuAc and sialyllactoses. In this review, we first discussed the application of NeuAc and sialyllactoses. Secondly, metabolic engineering and protein engineering-fueled progress of whole-cell catalysis and de novo synthesis of NeuAc and sialyllactoses were systematically summarized and compared. Furthermore, challenges of efficient microbial production of NeuAc and sialyllactoses as well as strategies for overcoming the challenges were discussed, such as clustered regularly interspaced short palindromic repeats interference (CRISPRi)-aided identification of key precursor transport pathways, synergistically debottleneck of kinetic and thermodynamic limits in synthetic pathways, and dynamic regulation of metabolic pathways for balancing cell growth and production. We hope this review can further facilitate the understanding of limiting factors that hampered efficient production of sialic acid and sialyllactoses, as well as contribute to the development of strategies for the construction of efficient production hosts for high-level production of sialic acid and sialyllactose based on synthetic biology tools and strategies.     

Predicting drug-target interactions using Lasso with random forest based on evolutionary information and chemical structure

The identification of drug-target interactions has great significance for pharmaceutical scientific research. Since traditional experimental methods identifying drug-target interactions is costly and time-consuming, the use of machine learning methods to predict potential drug-target interactions has attracted widespread attention. This paper presents a novel drug-target interactions prediction method called LRF-DTIs. Firstly, the pseudo-position specific scoring matrix (PsePSSM) and FP2 molecular fingerprinting were used to extract the features of drug-target. Secondly, using Lasso to reduce the dimension of the extracted feature information and then the Synthetic Minority Oversampling Technique (SMOTE) method was used to deal with unbalanced data. Finally, the processed feature vectors were input into a random forest (RF) classifier to predict drug-target interactions. Through 10 trials of 5-fold cross-validation, the overall prediction accuracies on the enzyme, ion channel (IC), G-protein-coupled receptor (GPCR) and nuclear receptor (NR) datasets reached 98.09%, 97.32%, 95.69%, and 94.88%, respectively, and compared with other prediction methods. In addition, we have tested and verified that our method not only could be applied to predict the new interactions but also could obtain a satisfactory result on the new dataset. All the experimental results indicate that our method can significantly improve the prediction accuracy of drug-target interactions and play a vital role in the new drug research and target protein development. The source code and all datasets are available at https://github.com/QUST-AIBBDRC/LRF-DTIs/ for academic use.     

Extracellular vesicles derived from Echinococcus granulosus hydatid cyst fluid from patients: isolation,characterization and evaluation of immunomodulatory functions on T cells

Cystic echinococcosis is a chronic and complex zoonotic disease. The mechanisms underlying the parasite’s establishment, growth and persistence are not completely understood, and are thought be modulated by a crosstalk through extracellular vesicles. Here, EVs were isolated from the hydatid cyst fluid of patients with cystic echinococcosis and protoscolex culture supernatant. Proteomic analysis of these EVs revealed several parasite- and human-derived proteins. Very few studies have performed proteomic analysis of EVs isolated from HCF and PCS. Our proteomic analysis of the EVs derived from HCF and PCS facilitated identification of 1175 proteins, wherein 1026 and 38 proteins were exclusively identified in the EVs derived from HCF (HCF-EVs) and PCS (PCS-EVs), respectively, and 111 proteins were shared in both. The results of co-culture of PCS-EVs with murine peripheral blood mononuclear cells showed that PCS-EVs significantly regulated T lymphocyte functions in a dose-dependent manner. Collectively, our results provide valuable information on parasite survival strategies and new insights into the role of these EVs in the establishment and persistence of hydatid cysts.     

Heat exposure affected the reproductive performance of pregnant mice: Enhancement of autophagy and alteration of subcellular structure in the corpus luteum

To investigate whether autophagy and subcellular changes are involved in the corpus luteum after heat exposure, a total of 30 early pregnant mice were divided equally into heat stress (HS) and non-HS (NHS) groups (n = 15). Mice in the HS group were exposed to 40.5 ± 0.2 ℃ for 7 consecutive days. Ovaries were collected for immunohistochemistry (IHC), western blot (WB) analysis and transmission electron microscopy (TEM). Serum was collected to determine progesterone by RIA and uteri were collected to count the implantation sites. Results showed that heat exposure increased rectal temperature, decreased body weight and number of implantation sites. WB analysis revealed that ovarian expression of LC3B and Atg7 was up-regulated, while p62 was down-regulated in the HS group. IHC results demonstrated that ovarian staining intensity of LC3B was more intense in the HS group than that of the NHS group. LC3B was mainly localized in the granulosa cells, oocytes and luteal steroidogenic cells of the HS group. TEM results revealed double-layered separated membranes indicative of autophagosomes in the luteal steroidogenic cells of the HS group. Moreover, TEM showed that the mitochondrial cristae became dearth, structure-less, swollen after HS. Additionally, the nucleus expanded and accumulation of lipid droplets increased after HS. Results also showed that heat exposure decreased serum progesterone level and ovarian P450scc expression. These results indicate that HS enhanced autophagy and altered the subcellular structure of luteal steroidogenic cells, which may contribute to interfering with the maintenance of luteal function in early pregnant mice.     

Advances in thermochemical conversion of woody biomass to energy,fuels and chemicals

Biomass has been recognised as a promising resource for future energy and fuels. The biomass, originated from plants, is renewable and application of its derived energy and fuels is close to carbon-neutral by considering that the growing plants absorb CO₂ for photosynthesis. However, the complex physical structure and chemical composition of the biomass significantly hinder its conversion to gaseous and liquid fuels.This paper reviews recent advances in biomass thermochemical conversion technologies for energy, liquid fuels and chemicals. Combustion process produces heat or heat and power from the biomass through oxidation reactions; however, this is a mature technology and has been successfully applied in industry. Therefore, this review will focus on the remaining three thermochemical processes, namely biomass pyrolysis, biomass thermal liquefaction and biomass gasification. For biomass pyrolysis, biomass pretreatment and application of catalysts can simplify the bio-oil composition and retain high yield. In biomass liquefaction, application of appropriate solvents and catalysts improves the liquid product quality and yield. Gaseous product from biomass gasification is relatively simple and can be further processed for useful products. Dual fluidised bed (DFB) gasification technology using steam as gasification agent provides an opportunity for achieving high hydrogen content and CO₂ capture with application of appropriate catalytic bed materials. In addition, multi-staged gasification technology, and integrated biomass pyrolysis and gasification as well as gasification for poly-generation have attracted increasing attention.     

A new trogiid genus from lower Eocene Fushun amber (Insecta: Psocodea: Trogiomorpha)

A new fossil brachypterous psocid tax on belonging to the family Trogiidae is characterized, illustrated and described from the early Eocene Fushun amber. Paralepinotus fushunensis nov. gen., nov. sp., shares several characters with the genus Lepinotus von Heyden, 1850, but differs from it mainly by the presence of tibial spurs other than apical ones and the absence of a forked sensillum on the last maxillary palp. This fossil taxon is also characterized by relatively developed elytriform forewing but still not reaching the tip of the abdomen. A checklist of all known Trogiidae is provided.     

Advances in 2-phenylethanol production from engineered microorganisms

2-Phenylethanol (2-PE) is an important flavor ingredient with a rose-like odor. Due to concerns about the toxic byproducts potentially found in 2-PE from chemical synthesis, consumers prefer the natural aroma compound, promoting the biosynthesis of 2-PE. Various microorganisms produce 2-PE naturally with low yield. Recent metabolic engineering strategies in yeasts and Escherichia coli have achieved great success in improving 2-PE bioproduction, including the alleviation of feed-back inhibition, improvement of precursor transport, enhancing activities of crucial enzymes, and reduction of by-products. Here, we review the metabolic engineering strategies applied to microorganisms for increasing bioproduction of 2-PE, address current problems, and propose further improvements.     

Middle Jurassic Ginkgo leaves from the Daohugou area,Inner Mongolia,China and their implication for palaeo-CO2 reconstruction

Well-preserved Ginkgo leaves with cuticle were collected from the Middle Jurassic Jiulongshan Formation in the Daohugou area, Inner Mongolia, China, which form the common elements in the Daohugou flora. Three new species of Ginkgo are recognized and their leaf morphology and cuticular structure are described for the first time. Two different pCO₂ proxy models were applied to reconstruct palaeo-atmospheric CO₂ concentration by using these new Ginkgo material. NLE (nearest living equivalent) suggests a semi-quantitative pCO₂ estimate as 839 ± 99 ppmv with Carboniferous standardization and 419 ± 49 ppmv with Recent standardization. While Barclay’s revised SI-pCO₂ regression suggests the estimates as 405 ± 71 ppmv. The results show that the pCO₂ estimate is higher than today’s atmospheric CO₂ concentration but lower than most of the other results on the Jurassic Period. Combined with the floristic composition, the climate at 165 Ma in the Daohugou area is inferred to be warm temperate.