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Thiocyanate (SCN−) is a nitrogen-containing pollutant, which can be involved in the nitrogen (N) cycle and interferes with plant growth. The current study highlights a new insight into the N (nitrate [NO3-] and ammonium [NH4+]) utilization ways in rice seedlings under SCN− exposure to clarify the interactive effect on uptake and assimilation between these N-containing chemicals. Phenotypically, relative growth rates (RGR) of NO3−-fed seedlings were significantly higher than NH4+-fed rice seedlings at the same SCN− concentration. Both N fertilizations have no significant influence on SCN− content and its assimilation in rice seedlings. However, significant accumulation of NO3− and NH4+ were detected in shoots prior to roots under SCN− stress. Enzymatic assay and mRNA analysis showed that the carbonyl sulfide (COS) pathway of SCN− degradation occurred in both roots and shoots of NO3−-fed seedlings but only evident in roots of NH4+-fed seedlings. Moreover, the effect of SCN− on the activity of nitrate reductase (NR), glutamine synthetase (GS), and glutamate synthase (GOGAT) was negligible in NO3−-fed seedlings, while GOGAT activity was significantly inhibited in shoots of NH4+-fed seedlings. Nitrogen use efficiency (NUE) estimation provided positive evidence in utilizing NO3− over NH4+ as the main N source to support rice seedling growth during detoxification of exogenous SCN−. Overall, SCN− pollution has unexpectedly changed the rice preference for N source which shifted from NH4+ to NO3−, suggesting that the interactions of SCN− with different N sources in terms of uptake and assimilation in rice plants should not be overlooked, especially at the plant N nutritional level.

Although the PVR/TIGIT immune checkpoint axis has been suggested as a promising target for cancer immunotherapy and multiple TIGIT-targeting therapies are undergoing clinical trials, the underlying regulatory mechanisms of PVR/TIGIT interaction remain inconclusive. Here we show that TIGIT N-glycosylations are critical for maintaining the interaction between TIGIT and PVR. TIGIT has two N-glycosylation residues, N32 and N101. N-glycosylation on N101 of TIGIT and, to less extent, on N32, play potent roles in PVR binding. Taken together, these findings suggest that the N-glycosylation sites on TIGIT, especially residue N101, may be potential targets for PVR/TIGIT immune checkpoint blockade.

A novel redox-active Schiff base polymer (SBPPPDA-PDA) was prepared by condensation of p-phenylenediamine with 1,10-phenanthroline-2,9-dicarbaldehyde. The structure of SBPPPDA-PDA was investigated by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, N2 adsorption/desorption isotherm, and powder X-ray diffraction and electrochemical techniques. The results showed that SBPPPDA-PDA had two-dimensional lamellar structure. The electrochemical properties of SBPPPDA-PDA were characterized by cyclic voltammetry, showing several pairs of redox peaks and good catalytic ability toward oxygen reduction. On the basis of the redox-active activity of SBPPPDA-PDA, an electrochemical pH sensor was proposed based on SBPPPDA-PDA with a linear range from 2 to 9 for pH detection. With nitrogen-containing skeleton and porous structure, SBPPPDA-PDA could be used as support to load glucose oxidase (GOD). Thus, a novel ratiometric electrochemical glucose sensor was further constructed by immobilizing GOD on SBPPPDA-PDA modified electrode. The results revealed that the reduction peak of O2 decreased with the gradual addition of glucose, while the response peak of SBPPPDA-PDA at about 0.15 V almost remained. The sensor based on GOD/SBPPPDA-PDA/SPE showed a rapid response, a linear range from 22.5 μmol/L–5 mmol/L and a lower detection limit of 7.56 μmol/L for glucose.

The Salvia miltiorrhiza and Panax notoginseng herb pair (DQ) has been widely utilized in traditional Chinese medicine for the longevity and for preventing and treating cardio-cerebrovascular diseases. Often associated with cardio-cerebrovascular diseases are comorbidities such as insulin resistance. However, the protective mechanisms of DQ against insulin resistance remain not well understood. Through network pharmacology analysis, a total of 94 candidate active compounds selected from DQ (61 from S. miltiorrhiza Bunge and 33 from P. notoginseng (Burk.) F. H. Chen) interacted with 52 corresponding insulin resistance-related targets, which mainly involved insulin resistance and the AMPK signaling pathway. Furthermore, the contribution index calculation results indicated 25 compounds as the principal components of this herb pair against insulin resistance. Among them, ginsenoside F2, protocatechuic acid, and salvianolic acid B were selected and validated to promote glucose consumption through activating AMPK phosphorylation and upregulating GLUT4 in insulin-resistant cell model (HepG2/IR) cells. These findings indicated that DQ has the potential for repositioning in the treatment of insulin resistance mainly through the AMPK signaling pathway.

The fall armyworm (FAW), Spodoptera frugiperda (J. E. Smith), is native to the Americas. It has rapidly invaded 47 African countries and 18 Asian countries since the first detection of invasion into Nigeria and Ghana in 2016. It is regarded as a super pest based on its host range (at least 353 host plants), its inherent ability to survive in a wide range of habitats, its strong migration ability, high fecundity, rapid development of resistance to insecticides/viruses and its gluttonous characteristics. The inherently superior biological characteristics of FAW contribute to its invasiveness. Integrated pest management (IPM) of FAW has relied on multiple applications of monitoring and scouting, agricultural control, chemical pesticides, viral insecticides, sex attractants, bio-control agents (parasitoids, predators and entomopathogens) and botanicals. Knowledge gaps remain to be filled to: (1) understand the invasive mechanisms of S. frugiperda; (2) understand how to prevent its further spread and (3) provide better management strategies. This review summarizes the biological characters of FAW, their association with its invasiveness and IPM strategies, which may provide further insights for future management.

Background Long noncoding RNAs (lncRNAs) have emerged as an important class of transcriptional regulators in cellular processes. The past decades have witnessed great progress in lncRNA studies in a variety of organisms. The codling moth (Cydia pomonella L.) is an important invasive insect in China. However, the functional impact of lncRNAs in this insect remains unclear. In this study, an atlas of codling moth lncRNAs was constructed based on publicly available RNA-seq datasets. Results In total, 9875 lncRNA transcripts encoded by 9161 loci were identified in the codling moth. As expected, the lncRNAs exhibited shorter transcript lengths, lower GC contents, and lower expression levels than protein-coding genes (PCGs). Additionally, the lncRNAs were more likely to show tissue-specific expression patterns than PCGs. Interestingly, a substantial fraction of the lncRNAs showed a testis-biased expression pattern. Additionally, conservation analysis indicated that lncRNA sequences were weakly conserved across insect species, though additional lncRNAs with homologous relationships could be identified based on synteny, suggesting that synteny could be a more reliable approach for the cross-species comparison of lncRNAs. Furthermore, the correlation analysis of lncRNAs with neighbouring PCGs indicated a stronger correlation between them, suggesting potential cis-acting roles of these lncRNAs in the regulation of gene expression. Conclusions Taken together, our work provides a valuable resource for the comparative and functional study of lncRNAs, which will facilitate the understanding of their mechanistic roles in transcriptional regulation.

Research in the last few years has revealed that leukaemic cells can remodel the bone marrow niche into a permissive environment favouring leukaemic stem cell expansion. Tumour‐associated macrophages (TAMs) are prominent components of the tumour microenvironment and play an important role in the onset and progression of solid tumours. However, little is known about their role in the development of acute lymphoblastic leukaemia (ALL). Using a unique mouse model of T‐ALL induced by injection of EL4 T‐cell lymphoma cells to syngeneic C57BL/6 mice, we report herein that ALL leads to the invasion of leukaemia‐associated monocyte‐derived cells (LAMs) into the bone marrow and spleen of T‐ALL mice. Furthermore, we found that leukaemia cells could polarize bone marrow–derived macrophages (BMDMs) into LAMs. In turn, LAMs were able to protect leukaemia cells from drug‐induced apoptosis in vitro. Therapies targeted against the TAMs by inhibiting colony stimulating factor‐1 receptor (CSF‐1R) have emerged as a promising approach for cancer treatment. In this study, we demonstrate that CSF‐1R inhibition inhibits the viability of BMDMs, blocks LAMs polarization and reduces the abundance of LAMs in T‐ALL mice. In vivo, combination treatment of CSF‐1R inhibitor and vincristine (VCR) dramatically increased the survival of T‐ALL mice and delayed leukaemia progression compared with VCR monotherapy. Finally, these data reinforce the role of microenvironments in leukaemia and suggest that macrophages are a potential target for the development of novel therapeutic strategies in T‐ALL.

The bacterial communities of arthropods play important roles in the growth and development of their hosts, such as by providing nutrition or protecting against parasites and pathogens. However, for Tetranychus truncatus, a major crop pest, very little is known about its bacterial community. To understand the effects of the bacterial community in T. truncatus, mites were fed bean leaves that had been soaked in different concentrations of tetracycline hydrochloride (5 mg to 5 g per L). Antibiotic treatment had a negative impact on the fitness of T. truncatus, decreasing its fecundity and longevity. However, we could not exclude the possibility that the decrease in fecundity was due to a toxic effect of the antibiotic. 16S rRNA genes analyses showed that the antibiotic treatment did not significantly affect the diversity of bacterial species, but it did significantly change their relative abundances. Furthermore, predicted functions of microbiota were also changed with antibiotic treatment and the most abundant genes were related to metabolism. Our research revealed that the antibiotic induced change of bacterial communities mostly decreased the fecundity of T. truncatus, although we couldn't totally exclude the direct toxin of antibiotics on spider mites.

Refining oil contaminants are complex and cause serious harm to the environment. Remediation of refining oil-contaminated soil is challenging but has significant impact in China. Two plant species Agropyron fragile (Roth) P. Candargy and Avena sativa L. and one bacterium Bacillus tequilensis ZJ01 were used to investigate their efficiency in remediating the refining oil-polluted soil sampled from an oil field in northern China. The simulated experiments of remediations by A. fragile or A. sativa alone and A. fragile or A. sativa combined with B. tequilensis ZJ01 for 39 days and by B. tequilensis ZJ01 alone for 7 days were performed in the laboratory, with B. tequilensis ZJ01 added before or after the germination of seeds. Seed germination rates and morphological characteristics of the plants, along with the varieties of oil hydrocarbons in the soil, were recorded to reflect the remediation efficiency. The results showed that the contamination was weakened in all experimental groups. A. sativa was more sensitive to the pollutants than A. fragile, and A. fragile was much more resistant to the oil hydrocarbons, especially to aromatic hydrocarbons. Adding B. tequilensis ZJ01 before the germination of seeds could restrain the plant growth while adding after the germination of A. fragile seeds notably improved the remediation efficiency. The degradation rate of oil hydrocarbons by B. tequilensis ZJ01 alone was also considerable. Together, our results suggest that the unitary remediation by B. tequilensis ZJ01 and the binary remediation by A. fragile combined with B. tequilensis ZJ01 added after the germination of seeds are recommended for future in situ remediations.

BACKGROUND: Herbivore‐associated bacterial symbionts can change plant physiology and influence herbivore fitness. The spider mite Tetranychus truncatus is a notorious pest harboring various bacterial symbionts; however, the effect of bacterial symbionts on host plant physiology remains unclear. Here, we investigated whether infection with the endosymbionts Wolbachia and Spiroplasma altered spider mite performance on tomato plants and affected plant‐induced defenses. RESULTS: Wolbachia and Spiroplasma were mainly located in the gnathosoma and ovaries of their spider mite hosts. Wolbachia and Spiroplasma significantly improved spider mite reproductive performance in cultivated and wild‐type tomato. However, in plants deficient in jasmonic acid (JA) and salicylic acid (SA), there were no significant differences in reproduction between spider mites infected with Wolbachia and Spiroplasma and uninfected mites. The results indicated that the reproduction benefits conferred by endosymbionts may relate to plant defenses. Both spider mites infected with Wolbachia and Spiroplasma and uninfected mites induced similar levels of JA and SA accumulation in tomato, whereas tomato plants damaged by spider mites infected with both Wolbachia and Spiroplasma showed lower expression levels of JA‐ and SA‐responsive genes than those damaged by uninfected spider mites. In addition, mites infected with Wolbachia and Spiroplasma mites consumed more tomato amino acids compared to uninfected spider mites, which may have contributed to host fecundity. CONCLUSIONS: Our results suggest that the reproduction benefits conferred by endosymbionts may be associated with changes in plant defense parameters and the concentrations of plant amino acids. The results highlight the importance of endosymbionts in interactions between spider mites and their host plants. © 2020 Society of Chemical Industry

Twenty-six alkaloids, including the new taberines A–I (1–9), were obtained from Tabernaemontana corymbosa. The structures and absolute configurations were elucidated via MS, NMR, and ECD spectrosco...

A highly efficient di-C-glycosyltransferase GgCGT was discovered from the medicinal plant Glycyrrhiza glabra. GgCGT catalyzes a two-step di-C-glycosylation of flopropione-containing substrates with conversion rates of >98%. To elucidate the catalytic mechanisms of GgCGT, we solved its crystal structures in complex with UDP-Glc, UDP-Gal, UDP/phloretin, and UDP/nothofagin, respectively. Structural analysis revealed that the sugar donor selectivity was controlled by the hydrogen-bond interactions of sugar hydroxyl groups with D390 and other key residues. The di-C-glycosylation capability of GgCGT was attributed to a spacious substrate-binding tunnel, and the G389K mutation could switch di- to mono-C-glycosylation. GgCGT is the first di-C-glycosyltransferase with a crystal structure, and the first C-glycosyltransferase with a complex structure containing a sugar acceptor. This work could benefit the development of efficient biocatalysts to synthesize C-glycosides with medicinal potential.

Abiotic stress like drought and heavy metal imposes a negative impact on exposed plants’ growth and development, commences over production of reactive oxygen species (ROS) inside plant cells resulting in oxidative stress at the cellular level. After that, plants activate multiple defense mechanisms, within which the superoxide dismutase (SOD) family acts as the first line of defense to eliminate ROS. From the literature, it is evident that fewer studies have been carried out in combination with molecular evolution and phylogenetics, and expression profile of the SOD genes amidst dicot and the monocot at subcellular level against drought stress and cadmium (Cd) metal exposure. In the present study, SOD isogenes are identified in purposely elected two dicot plants i.e. Arabidopsis thaliana (9 genes), Solanum lycopersicum (8 genes) and two monocot plants namely Triticum aestivum (11 genes), and Oryza sativa (7 genes), respectively. Based on the amino acids sequence similarities, the identified proteins are classified into three subfamilies in accordance to their phylogenetic relationships, namely Cu/ZnSOD, FeSOD, and MnSOD. High variability observed between Cu/ZnSOD with other two groups i.e. FeSOD and MnSOD which showed lesser variation within them by using secondary structure predication. Subcellular localization suggested that genes encoding FeSOD, MnSOD and Cu/ZnSOD are predominant in chloroplasts, mitochondria, and cytoplasm, respectively in studied plants. The expression profiling through microarray analysis showed varied strategies of SOD isogenes against drought stress and Cd exposure individually. From the perspective of evolution, this study would expand our knowledge for vividly understanding the role of distinctive SOD isogenes in detoxifying ROS in different plants under various abiotic stresses.

In this study, the embryonic development of Syngnathus schlegeli is first described based on external morphological characteristics and then the genetic relationship between embryos is investigated using a microsatellite-based approach. Embryonic development proceeds from fertilized egg to prerelease of larva and can be categorized into four periods: early embryogenesis, eye development, snout formation and larva, which can be further divided into 15 stages. Embryos in the brood pouch are all in the same developmental stage. However, multi-maternity is observed in all sampled broods. Microsatellite-based parentage analysis suggests that pregnant males had, per male, mated with and received eggs from 3 to 7 females, with average being 4.3. The embryos of full sibs within a brood pouch were clustered, and seven patterns of parentage were observed. Combining previous studies with the evidence obtained from genotyped eggs inside the brood pouch in this study, we can confirm that the mating pattern of S. schlegeli is polygamous.

Two new guaiane sesquiterpenes, 7-(1-hydroxyethyl)-4-methyl-1-azulenecarboxaldehyde (1) and 7-isopropenyl-4-methyl-1-azulenecarboxylic acid (2), together with 5 known sesquiterpenes, were isolated ...

Heme oxygenase-1 (HO-1) is an inducible cytoprotective enzyme that degrades heme into free iron, carbon monoxide and biliverdin, which is then rapidly converted into bilirubin. These degradation products serve an important role in the regulation of inflammation, oxidative stress and apoptosis. While the expression level of HO-1 is typically low in most cells, it may be highly expressed when induced by a variety of stimulating factors, a process that contributes to the regulation of cell homeostasis. In the 5′-non-coding region of the HO-1 gene, there are two polymorphic sites, namely the (GT)n dinucleotide and T(−413)A single nucleotide polymorphism sites, which regulate the transcriptional activity of HO-1. These polymorphisms have been shown to be closely associated with the occurrence and progression of numerous diseases, including cardiovascular, pulmonary, liver and kidney, various types of cancer and viral diseases. The present article reviews the progress that has been made in research on the association between the two types of polymorphisms and these diseases, which is expected to provide novel strategies for the diagnosis, treatment and prognosis of various diseases.

Angiogenesis plays an important role in the growth and metastasis of solid tumors including melanoma. Inhibiting tumor-associated angiogenesis is a tactic in treating melanoma. Dioscin restrains angiogenesis in colon tumor and has anti-melanoma effects in cell and animal models. In a previous study, we found that dioscin inhibits Src/STAT3 signaling in melanoma cells. Activation of the Src/STAT3 pathway has been shown to promote tumor angiogenesis. This study aimed to determine whether dioscin's anti-melanoma effects is related to inhibiting Src/STAT3 signaling-mediated angiogenesis. In a B16F10 allograft mouse model, we found that dioscin inhibited melanoma growth and angiogenesis. To exclude the impact of tumor growth on angiogenesis, a chicken chorioallantoic membrane (CAM) model was used to verify the anti-angiogenic effect of dioscin. Results showed that dioscin suppressed vessel formation in CAM. To determine if tumor secreted pro-angiogenic cytokines are involved in the anti-angiogenic effect of dioscin, conditioned media from dioscin-treated A375 melanoma cells were used to culture human umbilical vein endothelial cells (HUVECs), and tube formation was monitored. It was observed that the tube formation of HUVECs was inhibited. Mechanistic studies revealed that dioscin inhibited the activation of Src and STAT3, and lowered mRNA and protein levels of STAT3 transcriptionally-regulated genes, in B16F10 melanomas. ELISA assays showed that dioscin decreased the secretion of MMP-2, MMP-9 and VEGF from A375 cells. Over-activation of STAT3 lessened the effects of dioscin in decreasing the secretion of pro-angiogenic cytokines from melanoma cells, and in inhibiting tube formation of HUVECs cultured with conditioned media from melanoma cell cultures. In summary, we for the first time demonstrated that inhibiting Src/STAT3 signaling-mediated angiogenesis is involved in the anti-melanoma effects of dioscin. This study provides further pharmacological groundwork for developing dioscin as an anti-melanoma agent.

Phototropins, namely, phototropin 1 (phot1) and phototropin 2 (phot2), mediate chloroplast movement to maximize photosynthetic efficiency and prevent photodamage in plants. Phot1 primarily functions in chloroplast accumulation process, whereas phot2 mediates both chloroplast avoidance and accumulation responses. The avoidance response of phot2-mediated chloroplasts under high-intensity blue light (HBL) limited the understanding of the function of phot1 in the chloroplast accumulation process at the HBL condition. In this study, we showed that the phot2 mutant exhibits a chloroplast accumulation response under HBL, which is defective when the root phototropism 2 (RPT2) gene is mutated in the phot2 background, mimicking the phenotype of the phot1 phot2 double mutant. A further analysis revealed that the expression of RPT2 was induced by HBL and the overexpression of RPT2 could partially enhance the chloroplast accumulation response under HBL. These results confirmed that RPT2 also participates in regulating the phot1-mediated chloroplast accumulation response under HBL. In contrast, RPT2 functions redundantly with neural retina leucine zipper (NRL) protein for chloroplast movement 1 (NCH1) under low-light irradiation. In addition, no chloroplast accumulation response was detected in the phot2 jac1 double mutant under HBL, which has been previously observed in phot2 rpt2 and phot1 phot2 double mutants. Taken together, our results indicated that phot1 mediates the HBL-induced chloroplast accumulation response in an RPT2-dependent manner and is also regulated by j-domain protein required for chloroplast accumulation response 1 (JAC1).

The surge of COVID-19 infection cases is spurred by emerging SARS-CoV-2 variants such as B.1.617. Here we report 38 cryo-EM structures, corresponding to the spike protein of the Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Kappa (B.1.617.1) variants in different functional states with and without its receptor, ACE2. Mutations on the N-terminal domain not only alter the conformation of the highly antigenic supersite of the Delta variant, but also remodel the glycan shield by deleting or adding N-glycans of the Delta and Gamma variants, respectively. Substantially enhanced ACE2 binding was observed for all variants, whose mutations on the receptor binding domain modulate the electrostatics of the binding interfaces. Despite their abilities to escape host immunity, all variants can be potently neutralized by three unique antibodies.

The process of soybean fermentation has been practiced for more than 3,000 years. Although Dajiang and Sufu are two popular fermented soybean products consumed in North China, limited information is available regarding their microbial composition. Hence, the current study sought to investigate, and compare, the physicochemical indicators and microbial communities of traditional Dajiang and Sufu. Results showed that the titratable acidity (TA), and salinity, as well as the lactic acid, and malic acid contents were significantly higher in Sufu samples compared to Dajiang. Furthermore, Sufu samples contain abundant sucrose and fructose, while the acetic acid content was lower in Sufu compared to Dajiang samples. Moreover, the predominant bacterial phyla in Dajiang and Sufu samples were Firmicutes and Proteobacteria, while the major genera comprise Bacillus, Lactobacillus, Tetragenococcus, and Weissella. Moreover, Dajiang samples also contained abundant Pseudomonas, and Brevundimonas spp., while Halomonas, Staphylococcus, Lysinibacillus, Enterobacter, Streptococcus, Acinetobacter, and Halanaerobium spp. were abundant in Sufu samples. At the species level, Bacillus velezensis, Tetragenococcus halophilus, Lactobacillus rennini, Weissella cibaria, Weissella viridescens, Pseudomonas brenneri, and Lactobacillus acidipiscis represented the major species in Dajiang, while Halomonas sp., Staphylococcus equorum, and Halanaerobium praevalens were the predominant species in Sufu. Acetic acid and sucrose were found to be the primary major physicochemical factor influencing the bacterial communities in Dajiang and Sufu, respectively. Furthermore, Bacillus subtilis is strongly correlated with lactic acid levels, L. acidipiscis is positively correlated with acetic acid levels, while Staphylococcus sciuri and S. equorum are strongly, and positively, correlated with malic acid. Following analysis of carbohydrate and amino acid metabolism in all samples, cysteine and methionine metabolism, as well as fatty acid biosynthesis-related genes are upregulated in Dajiang compared to Sufu samples. However, such as the Staphylococcus, W. viridescens, and P. brenneri, as potentially foodborne pathogens, existed in Dajang and Sufu samples. Cumulatively, these results suggested that Dajiang and Sufu have unique bacterial communities that influence their specific characteristics. Hence, the current study provides insights into the microbial community composition in Dajiang and Sufu samples, which may facilitate the isolation of functional bacterial species suitable for Dajiang and Sufu production, thus improving their production efficiency.

Two biphenyl-type neolignans with a rare dibenzofuran skeleton, including a new one piyunneolignan A (1) and a known one piperneolignan D (2), together with a new sesquiterpenoid piyunin A (3), were isolated from the leaves and twigs of Piper yunnanense. Their structures were established on the basis of comprehensive spectroscopic data analysis and electronic circular dichroism (ECD) calculation. Piyunneolignan A (1) featured a rare C-2-C-2'/C-3-O-C-3' linkage. Compounds 1-3 were evaluated for their antimicrobial and cytotoxic activities against a panel of bacteria, fungi, and human cancer cell lines, respectively.

Antibiotic resistance in bacteria has become a major global health problem. One of the main reservoirs of antibiotic resistance genes is the human gut microbiota. To characterise these genes, a metagenomic approach was used. In this study, a comprehensive antibiotic resistome catalog was established using fecal samples from 246 healthy individuals from world’s longevity township in Jiaoling, China. In total, 606 antibiotic resistance genes were detected. Our results indicated that antibiotic resistance genes in the human gut microbiota accumulate and become more complex with age as older groups harbour the highest abundance of these genes. Tetracycline resistance gene type tetQ was the most abundant group of antibiotic resistance genes in gut microbiota, and the main carrier of antibiotic resistance genes was Bacteroides. Antibiotic efflux, inactivation, and target alteration were found to be the dominant antimicrobial resistance mechanisms. This research may help to establish a comprehensive antibiotic resistance catalog that includes extremely long-lived healthy people such as centenarians, and may provide potential recommendations for controlling the use of antibiotics.

The interactive effects of six maturity stages and refrigerated storage (chilling)/blanching (heating) treatments on the volatile profiles of ripe tomatoes were studied. A total of 42 volatiles were identified, of which 19 compounds had odor activity values equal to or greater than 1. Of those, “green” and “leafy” aroma volatiles were most abundant. Chilling and heating treatments both suppressed overall volatile production, with chilling having the greater impact, regardless of harvest maturity. However, fruit harvested at the turning stage had the least volatile suppression by chilling and heating treatments in comparison with fruit harvested earlier or later, mostly in the fatty acid- and phenylalanine-derived volatiles. Volatiles derived from amino acids were promoted by heat treatment for fruit harvested at all maturities, and those derived from carotenoid and phenylalanine pathways and harvested at advanced harvest maturities were stimulated by chilling treatment. Volatile production is generally believed to be improved by delayed harvest, with vine-ripe being optimum. However, opposite results were observed possibly because the later-harvested fruit had longer exposure to open-field weather stress. The best harvest maturity recommendation is the turning stage where fruit developed abundant volatiles and were least impacted by chilling and heating treatments.

SummaryFANCD2 protein, a key coordinator and effector of the interstrand crosslink repair pathway, is also required to prevent excessive nascent strand degradation at hydroxyurea-induced stalled forks. The RAD51 recombinase has also been implicated in regulation of resection at stalled replication forks. The mechanistic contributions of these proteins to fork protection are not well understood. Here, we used purified FANCD2 and RAD51 to study how each protein regulates DNA resection at stalled forks. We showed that FANCD2 inhibits fork degradation in two ways: 1) the N-terminal domain of FANCD2 inhibits DNA2 nuclease activity by directly binding to DNA2. 2) independent of dimerization with FANCI, FANCD2 itself stabilizes RAD51 filaments to inhibit multiple nucleases, including DNA2, MRE11, and EXO1. Unexpectedly, we uncovered a new FANCD2 function: by stabilizing RAD51 filaments, FANCD2 acts as a “RAD51 modulator” to stimulate the strand exchange activity of RAD51. Our work biochemically explains non-canonical mechanisms by which FANCD2 and RAD51 protect stalled forks. We propose a model in which the strand exchange activity of FANCD2 provides a simple molecular explanation for genetic interactions between FANCD2 and the BRCA2 mediator in the FA/BRCA pathway of fork protection

Ethnopharmacological relevance The Danggui-Yimucao herb pair (DY) is a classic combination in Chinese herbal formulas, consisting of the root of Angelica sinensis (Oliv.) Diels and the aerial parts of Leonurus japonicus Houtt. DY first appeared in “Zhulinsi fuke mifang” in the Jin Dynasty, and it has a long history as a drug for the treatment of abortion. However, its underlying immunomodulatory mechanisms involved are still unclear. Aim of the study In this study, network pharmacology and pharmacological experiments were used to explore the role and mechanism of DY in the treatment of medical abortion. Materials and methods Network pharmacology was used to establish the relationship between the components of DY and abortion-related targets, and to enrich important pathways and biological process for verification. ELISA was used to assess progesterone levels. Flow cytometry was used to detect the degree of differentiation of Th1/Th2 cells. Immunohistochemical methods and qPCR were used to measure the expression levels of T-bet, GATA-3 and IL-4. Results Through the prediction analysis of network pharmacology, we found that key pathway for DY treatment of abortion, such as anemia, pelvic infection, immune disorders, and coagulation disorders, was Th1/Th2 cell differentiation pathway. The pharmacological results revealed that DY greatly corrected the imbalance of Th cell subsets in abortion mice, significantly inhibited the differentiation of Th2 cells, and resulted in an increase in the Th1/Th2 ratio. In addition, the concentration of progesterone in the serum of mice after abortion was significantly reduced. We also found that DY upregulated spleen T-bet and downregulated IL-4 gene expression in mice. Besides, immunohistochemical results showed that DYE could up-regulate T-bet but inhibit GATA-3 expression. Conclusions Our results showed that after RU486-induced abortion, progesterone and Th1/Th2 paradigm were disordered in mice, but DY could make mice recover more quickly, which indicated that DY had great development value in immunoregulation.

Heritable symbionts play an essential role in many aspects of host ecology in a temperature-dependent manner. However, how temperature impacts the host and their interaction with endosymbionts remains largely unknown. Here, we investigated the impact of moderate (20°C) and high (30 and 35°C) temperatures on symbioses between the spider mite Tetranychus truncatus and two maternally inherited endosymbionts (Wolbachia and Spiroplasma). We found that the thermal tolerance of mites (as measured by survival after heat exposure) was lower for mites that were singly infected with either Wolbachia or Spiroplasma than it was for co-infected or uninfected mites. Although a relatively high temperature (30°C) is thought to promote bacterial replication, rearing at high temperature (35°C) resulted in losses of Wolbachia and particularly Spiroplasma. Exposing the mites to 20°C reduced the density and transmission of Spiroplasma but not Wolbachia. The four spider mite strains tested differed in the numbers of heat shock genes (Hsps) induced under moderate or high temperature exposure. In thermal preference (Tp) assays, the two Wolbachia-infected spider mite strains preferred a lower temperature than strains without Wolbachia. Our results show that endosymbiont-mediated spider mite responses to temperature stress are complex, involving a combination of changing endosymbiont infection patterns, altered thermoregulatory behavior, and transcription responses.

Insect olfaction is vital for foraging, mating, host-seeking, and avoidance of predators/pathogens. In insects, odorant binding proteins (OBPs) are involved in transporting hydrophobic odor molecules from the external environment to receptor neurons. The codling moth, Cydia pomonella, one of the most destructive insect fruit pests, causes enormous economic losses. However, little is known about the number, variety, gains and losses, and evolution of OBP genes in C. pomonella. Here we report the identification of 40 OBPs in C. pomonella, most (75%) of which are classic OBPs, using genomic and transcriptomic analyses. Two OBP genes were lost in C. pomonella relative to possible distant ancestor in Lepidoptera lineage based on an analysis of gene gains and losses. The phylogenetic tree and chromosome location showed that the expansion of OBP genes mainly resulted from tandem duplications, as the CpomGOBP2 gene was duplicated twice along with loss of CpomPBPB. Two positive selection sites of the CpomGOBP1 gene were identified while other OBP genes evolved under purifying selection. Our results provide fundamental knowledge of OBP genes allowing further study of their function in C. pomonella.

Background Pseudocohnilembus persalinus and Uronema marinum (Ciliophora, Scuticociliatia), as parasitic scuticociliatid ciliates, were isolated from Scophthalmus maximus and Takifugu rubripes, respectively, in our previous studies. These ciliates are morphologically very similar; hence, it is difficult to identify specific scuticociliate species using traditional classification methods for performing taxonomic research and disease control studies. Methods We annotated the mitochondrial genomes of these two scuticociliates on the basis of previous sequencing, including analyses of nucleotide composition, codon usage, Ka/Ks, and p-distance. We also compared the nucleotide and amino acid similarity of the mitochondrial genomes of P. persalinus, U. marinum, and other 12 related ciliates, and a phylogenetic tree was constructed using 16 common genes. We chose the nad4 and nad7 genes to design specific PCR primers for identification. Results P. persalinus and U. marinum were found to have a close evolutionary relationship. Although codon preferences were similar, differences were observed in the usage of codons such as CGA, CGC, and GTC. Both Ka/Ks and p-distance were less than 1. Except for yejR, ymf57, ymf67, and ymf75, the amino acid sequence similarity between P. persalinus and U. marinum was greater than 50%. Conclusions The mitochondrial genomes of P. persalinus and U. marinum were thoroughly compared to provide a reference for disease prevention and control. The specific PCR primers enabled us to identify P. persalinus and U. marinum rapidly and accurately at the molecular level, thus providing a basis for classification and identification. Graphic abstract

The dynamic changes of wine ester production during mixed fermentation with Hanseniaspora uvarum Yun268 and Saccharomyces cerevisiae F5 was investigated at different levels and timings of nitrogen nutrient addition. Nitrogen additions were performed by supplementing yeast assimilable nitrogen (YAN) into a synthetic grape must with defined composition. Ester precursors and extracellular metabolites involved in ester synthesis were analyzed throughout the fermentation. Results showed that nitrogen additions covering 50–200 mg/L YAN at the point of yeast inoculation slightly affected yeast competition and ester profiles. Interestingly, when YAN was supplemented in the mid-stage, the survival of H. uvarum Yun268 was enhanced, resulting in more than a 2-fold increase in the levels of higher alcohol acetates compared to that at the initial stage. Furthermore, carbon fluxes may be redistributed in the central pathway, which contributed to the production of medium-chain fatty acids and eventually triggered a 1.2-fold elevation in corresponding ethyl ester levels.

Specific pathogen-free (SPF) experimental animals are recognized as standard laboratory animals in the fields of biomedical, animal husbandry and veterinary research and production. Intestinal flora plays a critical role in nutrient absorption, improving health and protecting the host from pathogens. We therefore explored the variation and maintenance of intestinal flora in SPF chicks in order to better understand the composition of intestinal microflorain SPF chickens, and provide reference for the study of intestinal flora of SPF experimental animals. Five chicks were randomly selected at each of 14, 28, and 42 days, and ceca were removed for DNA extraction. The Illumina Miseq platform was used for microbiome analysis of the V3-V4 region of the 16S rRNA gene. During the course of chick gut microbiome development, we observed major changes in diversity, especially between day 14 and day 28. Firmicutes, Proteobacteria, and Bacteroidetes were the main bacterial taxa, and Firmicutes increased significantly with age. The genus with the highest relative abundance was Lactobacillus, followed by Faecalibacterium. In addition, while abundance of Ruminococcaceae spp., Ruminococcus, and Blautia increased with age, Lactobacillus, Enterobacteriaceae spp., and Oscillospira decreased with age. Interestingly, the abundance of Faecalibacterium first increased and then decreased over time. The characteristics of SPF chicken gut flora at different ages establish a basis for the regulation of intestinal flora in the early stage of brooding, and also provide a theoretical foundation for controlling and preventing infections and poultry diseases in newborn chickens.

Juvenile hormone esterase (JHE) is a key enzyme for insects, playing an important role in the regulation of insect growth, development, diapause and reproduction. We identified a complete putative JHE of Cydia pomonella (CpJHE-like) which is comprised of a 1 761 bp coding sequence (CDS) encoding 587 amino acid residues from the transcriptome data. The deduced protein sequence of CpJHE-like showed the highest identity of 60.44% with the Adoxophyes honmai JHE (AhJHE) and the minimal identity of 25.81% with Aedes aegypti JHE (AaJHE). CpJHE-like exhibited all the seven typical motifs of the functional JHEs and had the highly consistent tertiary structure with Manduca sexta JHE (MsJHE). Phylogenetic analysis showed that the CpJHE-like was close to two JHEs from the family Tortricidae. The CpJHE-like transcript level take a leap in the 3-day-old fifth instar larva, increased about 300-fold compared to the basal level. Tissue-specific expression profile showed that the CpJHE-like transcript was expressed mainly in the fat body. This study indicates that the CpJHE-like is the functional JHE, which may play vital roles in the development and reproduction of C. pomonella.

Bacteria symbionts in herbivores play an important role in host biology and ecology, and are affected by environmental factors such as temperature, diet, habitat, antibiotics and so on. However, the effects of antibiotics on the microbiome of the small brown planthopper Laodelphax striatellus (SBPH) remain unclear. Here, we studied the effects of tetracycline on the diversity and composition of bacterial colonies in different tissues of SBPH using high throughput sequencing of 16S ribosomal RNA amplicons. Our results show that Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria were most abundant in SBPH, and the genera Asaia and Wolbachia were most abundant in all body parts of SBPH. Antibiotic treatment had persistent effects on the composition of the SBPH microbiome. Tetracycline depleted the population of Firmicutes, Bacteroidetes, Tenericutes and Fusobacteria, and nearly 100% eliminated Wolbachia, Bacteroides and Abiotrophia in SBPH. Together, these results suggest that antibiotic exposure affects the bacteria symbionts of different body parts in SBPH and will facilitate future studies of the bacterial symbionts of arthropod hosts.

Bone marrow-derived mesenchymal stem cells (BMSCs) exhibit potential regenerative effects on the injured brain. However, these effects are constrained by their limited ability to migrate to the injured site. Oncostatin M (OSM) has been shown to affect the proliferation and migration of mesenchymal stem cells. Therefore, in the present study, we explored whether OSM improves BMSC migration and secretion of growth factors and cytokines in a rat middle cerebral artery occlusion (MCAO) stroke model. The effect of OSM on the proliferation and apoptosis of rat BMSCs was first assessed in vitro, and the gene and secretion levels of factors related to cell nutrition and migration, such as SDF-1 and VEGF, were detected. To further explore underlying pathways triggered by OSM, BMSCs were treated with OSM in the presence or absence of inhibitors of the STAT3 and ERK pathways. Effects of OSM on SDF-1 expression in astrocytes and BMSC migration were also evaluated. In the rat MCAO model, OSM secretion levels were detected in the brain for up to 72 h after model establishment. Ventricle injection of OSM alone or OSM combined with caudal vein graft of BMSCs was then performed in MCAO stroke rats. After 72 h, production of SDF-1 and grafted BMSCs was detected in the lesion areas of the brain, and the nerve function score was evaluated. We found that the production of OSM continually increased in the brains of MCAO rats from 12 h to 72 h. OSM significantly upregulated SDF-1 in BMSCs via the STAT3 and ERK pathways and significantly promoted the expression of VEGF and MMP-2. OSM also promoted the secretion of SDF-1 in astrocytes through the STAT3 and ERK pathways to in turn enhance BMSC migration. Combination treatment with OSM and BMSCs in MCAO rats increased the migration efficiency of BMSCs in the brain, which significantly improved neurofunctional recovery while reducing the expression of inflammatory mediators and promoting the secretion of nutrition factors. Overall, these results show that OSM is highly expressed in the brains of MCAO stroke rats and can upregulate SDF-1 to promote BMSC migration. Thus, combination treatment with OSM and BMSCs improves the graft efficiency of BMSCs and neurofunctional recovery.

Constructed wetlands (CWs) usually exhibit limits in functional redundancy and diversity of microbial community contributing to lower performances of nutrients removal in decentralized domestic sewage treatment. To address this quandary, heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria was added in tidal flow CWs (TFCWs) developing for nitrogen (N) and phosphorus (P) removal. With addition of HN-AD bacteria, TFCWs could be setup more rapidly and obtained better removal efficiencies of 66.9%-70.1% total nitrogen (TN), and 88.2%-92.4% total phosphorus (TP) comparing with control systems (TN: 53.9%; TP: 83.9%) during stable operation. Typical-cycles variations showed that TFCWs with addition of HN-AD bacteria promoted NO3--N and NH4+-N removal respectively under hydraulic retention time (HRT) of 14 h and 8 h with slight NO2--N accumulation. Activated alumina (AA) coupled with HN-AD bacteria decreased P release and relieved its poor removal performance in CWs. Based on metagenomic taxa and functional annotation, Pseudomonas and Thauera played pivotal roles in N removal in TFCWs. Furthermore, gradient oxic environments by 8 h-HRT promoted co-occurrence of heterotrophic nitrifiers (mostly Pseudomonas stutzeri) and autotrophic nitrifiers (mostly Nitrosomonas europaea. and Nitrospira sp.) which potentially accelerated NH4+-N transformation by elevated nitrification and denitrification related genes (e. g. amoABC, hao, napA and nirS genes). Meanwhile, the addition of HN-AD bacteria stimulated nirA and gltD genes of N assimilation processes probably leading to NH4+-N directly removal. The conceptual model of multi-metabolism regulation by HN-AD process highlighted importance of glk, gap2 and PK genes in glycolysis pathway which were vital drivers to nutrients metabolism. Overall, this study provides insights into how ongoing HN-AD bacteria-addition effected microbial consortia and metabolic pathways, serving theoretical basis for its engineered applications of TFCWs in decentralized domestic sewage treatment.

Preventative effects of Lactobacillus fermentum and Bacillus coagulans against Clostridium perfringens infection in broilers have been well-demonstrated. The present study was conducted to investigate the modulation of these two probiotics on intestinal immunity and microbiota of C. perfringens-challenged birds. The 336 one-day-old broilers were assigned to four groups with six replicates in each group. Birds in the control were unchallenged and fed a basal diet, and birds in the three challenged groups were dietary supplemented with nothing (Cp group), 1 × 109 CFU/kg of L. fermentum (Lf_Cp group), or 1 × 1010 CFU/kg of B. coagulans (Bc_Cp group). Challenge was performed from days 14 to 20, and samples were collected on days 21 and 28. Challenge upregulated interleukin (IL)-1β and transforming growth factor (TGF)-β4 mRNA expression in jejunum on day 21, which was downregulated by B. coagulans and L. fermentum, respectively (P < 0.05). Both probiotic groups upregulated jejunal IL-1β, interferon (IFN)-γ, IL-17, and TGF-β4 on day 28 as well as IFN-γ on day 21 (P < 0.05). The Bc_Cp group increased CD3+ T cell counts in the jejunal crypt on day 21 (P < 0.05). Challenge decreased the ileal ACE index on day 21 and cecal microbial richness on day 28, which were increased by probiotic treatments, and ileal bacterial richness decreased in the Bc_Cp group on day 28 (P < 0.05). Only ileal microbiota on day 21 was distinctly affected with an R-value at 0.3116 by ANOSIM analysis (P < 0.05). Compared with the control, ileal Firmicutes increased on day 21, and ileal Bacteroidetes and cecal Proteobacteria decreased on day 28 in challenged groups (P < 0.05). Challenge increased Romboutsia spp. in the ileum as well as unclassified f_Lachnospiraceae and Ruminococcus_torques group in the cecum, and decreased Lactobacillus spp. in the ileum on day 21, which were all conversely modulated by L. fermentum (P < 0.05). Challenge increased amino acid metabolism of ileal microbiota and membrane transport of cecal microbiota, and decreased amino acid metabolism of cecal microbiota on day 21, which were conversely regulated by both probiotics (P < 0.05). In conclusion, L. fermentum and B. coagulans attenuated the intestinal inflammation and microbial dysbiosis soon after C. perfringens challenge.

Background: Guan-Xin-Shu-Tong capsule (GXSTC) is a traditional Chinese medicine (TCM) that has been used to treat coronary heart disease (CHD) for many years in China. However, the holistic mechanism of GXSTC against CHD is still unclear. Therefore, the purpose of this paper was to systematically explore the mechanism of action GXSTC in the treatment of CHD rats using a metabolomics strategy.Methods: A CHD model was induced by ligation of the left anterior descending coronary artery (LAD). In each group, echocardiography was performed; the contents of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) in serum were determined; and the myocardial infarct size was measured. The metabolites in plasma were analyzed by UHPLC-MS/MS-based untargeted metabolomics. Then, multivariate statistical analysis was performed to screen potential biomarkers associated with the GXSTC treatment in the LAD-induced rat CHD model. Finally, the MetaboAnalyst 4.0 platform was used for metabolic pathway enrichment analysis.Results: GXSTC was able to regulate the contents of CK, LDH and AST; restore impaired cardiac function; and significantly reduce the myocardial infarction area in model rats. Twenty-two biomarkers and nine metabolic pathways of GXSTC in the treatment of CHD were identified through UHPLC-MS/MS-based untargeted metabolomics analysis.Conclusion: GXSTC regulates metabolic disorders of endogenous components in LAD-induced CHD rats. The anti-CHD mechanism of GXSTC is mainly related to the regulation of amino acid, lipid and hormonal metabolism. This study provides an overall view of the mechanism underlying the action of GXSTC against CHD.

Background and purpose Pancreatic cancer is an exceptionally fatal disease. However, therapeutic drugs for pancreatic cancer have presented a serious shortage over the past few decades. Signal transducer and activator of transcription-3 (STAT3) is persistently activated in many human cancers where it promotes tumour development and progression. Natural products serve as an inexhaustible source of anticancer drugs. Here, we identified the natural product trienomycin A (TA), an ansamycin antibiotic, as a potential inhibitor of the STAT3 pathway with potent activity against pancreatic cancer. Experimental approach Effects of trienomycin A on transcriptional activity of STAT3 were assessed by the STAT3-luciferase (STAT3-luc) reporter system. In vitro and in vivo inhibitory activity of TA against pancreatic cancer made use of molecular docking, surface plasmon resonance (SPR) assay, MTS assay, colony formation assay, transwell migration/invasion assay, flow cytometric analysis, immunofluorescence staining, quantitative real-time polymerase chain reaction (PCR), western blotting, tumour xenograft model, haematoxylin and eosin (H&E) staining and immunohistochemistry. Key results Trienomycin A directly bound to STAT3 and inhibited STAT3 (Tyr705) phosphorylation, thus inhibiting the STAT3 pathway. Trienomycin A also inhibited colony formation, proliferation, migration and invasion of pancreatic cancer cell lines. Trienomycin A also markedly blocked pancreatic tumour growth in vivo. More importantly, trienomycin A did not show obvious toxicity at the effective dose in mice. Conclusions and implications Trienomycin A exerted anti-neoplastic activity by suppressing STAT3 activation in pancreatic cancer. This natural product could be a novel therapeutic candidate for pancreatic cancer.

Quassinoids, originating from the oxidative degradation of tetracyclic tirucallane triterpene, are a diverse class of secondary metabolites identifying from nature mostly in Simaroubaceae family. The crucial pharmacological activities and structural complexity of quassinoids have long fascinated scientists due to their medicinal uses, infamous toxicity, and unique biosynthesis. In the past few decades, 482 quassinoids, assigned to 6 skeletons, have been isolated and identified from plants. The names, classes, molecular formula, and plant sources of these secondary metabolites are collated here. This review will be a detailed update of the naturally occurring quassinoids reported from the plant kingdom, providing an in-depth discussion of their diversity, antitumor activities, structure-activity relationship.

The ocean contains ice nucleating substances (INSs), some of which can be emitted to the atmosphere where they can influence the formation and properties of clouds. A possible source of INSs in the ocean is exudates from sea-ice diatoms. Here we examine the concentrations and properties of INSs in supernatant samples from dense sea-ice diatom communities collected from Ross Sea and McMurdo Sound in the Antarctic. The median freezing temperatures of the samples ranged from approximately -17 to -22 °C. Based on our results and a comparison with results reported in the literature, the ice nucleating ability of exudates from sea-ice diatoms is likely not drastically different from the ice nucleating ability of exudates from temperate diatoms. The number of INSs per mass of DOC for the supernatant samples were lower than those reported previously for the sea surface microlayer and bulk sea water collected in the Arctic and Atlantic. The INSs in the supernatant sample collected from Ross Sea were not sensitive to temperatures up to 100 °C, were larger than 300 kDa, and were different from ice shaping and recrystallization inhibiting molecules present in the same sample. Possible candidates for these INSs include polysaccharide containing nanogels. The INSs in the supernatant sample collected from McMurdo Sound were sensitive to temperatures of 80 and 100 °C and were larger than 1000 kDa. Possible candidates for these INSs include protein containing nanogels.

Thiocyanate (SCN-) present in irrigation water can have negative effects on plant growth and crop yields. Addition of plant growth regulators (PGRs) can alleviate toxic stress to plants. In the current study, we established a grey situation decision-making model (GSDM) to integrate the data of RT-qPCR analysis for screening the optimal addition of PGRs to minimise pollution stress. The effects of PGRs (i.e., jasmonic acid [JA], indole-3-acetic acid [IAA] and sodium hydrosulfide [NaHS]) on the abundance of IAA oxidation and conjugation-related genes in rice seedlings under potassium thiocyanate (KSCN) exposure was examined. The results obtained from RT-qPCR analysis can roughly present the mitigating effects of IAA, JA, and NaHS on rice seedlings under KSCN stress. Integration of RT-qPCR analysis and GSDM further quantified the regulatory effects of PGRs. Simulation results showed that the effect of NaHS on the gene expression at KSCN exposure is apparently better than that of JA and IAA. Our study provides a new simple, efficient, and cheap approach to identify the optimal plant growth regulators under the stress of environmental pollution.

The unc-13 homolog B (UNC13B) gene encodes a presynaptic protein, mammalian uncoordinated 13-2 (Munc13-2), which is highly expressed in the brain—predominantly in the cerebral cortex—and plays an essential role in synaptic vesicle priming and fusion, potentially affecting neuronal excitability. However, the functional significance of the UNC13B mutation in human disease is not known. In this study, we screened for novel genetic variants in a cohort of 446 unrelated cases (families) with partial epilepsy without acquired causes by trio-based whole-exome sequencing. UNC13B variants were identified in 12 individuals affected by partial epilepsy and/or febrile seizures from eight unrelated families. The eight probands all had focal seizures and focal discharges in EEG recordings, including two patients who experienced frequent daily seizures and one who showed abnormalities in the hippocampus by brain MRI; however, all of the patients showed a favourable outcome without intellectual or developmental abnormalities. The identified UNC13B variants included one nonsense variant, two variants at or around a splice site, one compound heterozygous missense variant and four missense variants that cosegregated in the families. The frequency of UNC13B variants identified in the present study was significantly higher than that in a control cohort of Han Chinese and controls of the East Asian and all populations in the Genome Aggregation Database (gnomAD). Computational modelling, including hydrogen bond and docking analyses, suggested that the variants lead to functional impairment. In Drosophila, seizure rate and duration were increased by Unc13b knockdown compared to wild-type flies, but these effects were less pronounced than in sodium voltage-gated channel alpha subunit 1 (Scn1a) knockdown Drosophila. Electrophysiological recordings showed that excitatory neurons in Unc13b-deficient flies exhibited increased excitability. These results indicate that UNC13B is potentially associated with epilepsy. The frequent daily seizures and hippocampal abnormalities but ultimately favourable outcome under anti-epileptic therapy in our patients indicate that partial epilepsy caused by UNC13B variant is a clinically manageable condition., Wang et al. present clinical and experimental evidence suggesting that UNC13B is a novel epilepsy gene. They describe UNC13B mutations in 12 individuals affected by partial epilepsy and/or febrile seizures from eight unrelated families, and show seizure-like behaviour and increased neural firing in Unc13b knockdown flies.

Salicylic acid is a phenolic phytohormone which controls plant growth and development. A methyl ester (MSA) derivative thereof is volatile and involved in plant-insect or plant-plant communication. Here we show that the nematode-trapping fungus Duddingtonia flagrans uses a methyl-salicylic acid isomer, 6-MSA as morphogen for spatiotemporal control of trap formation and as chemoattractant to lure Caenorhabditis elegans into fungal colonies. 6-MSA is the product of a polyketide synthase and an intermediate in the biosynthesis of arthrosporols. The polyketide synthase (ArtA), produces 6-MSA in hyphal tips, and is uncoupled from other enzymes required for the conversion of 6-MSA to arthrosporols, which are produced in older hyphae. 6-MSA and arthrosporols both block trap formation. The presence of nematodes inhibits 6-MSA and arthrosporol biosyntheses and thereby enables trap formation. 6-MSA and arthrosporols are thus morphogens with some functions similar to quorum-sensing molecules. We show that 6-MSA is important in interkingdom communication between fungi and nematodes.

Two new sesquiterpenes, litseachrandaevanes C and D (1 and 2), together with five known sesquiterpenes (3 − 7), were isolated from the stems of Fissistigma glaucescens (Hance) Merr. Their structures were elucidated using comprehensive spectroscopic methods. The inhibitory effect of all compounds on the proliferation of primary synovial cells was evaluated. Compound 3 showed inhibitory effect on the proliferation of synoviocytes, with an IC50 value of 12.5 μM.

The blood vascular system is a tree-like hierarchical branching structure and needs to function even before fully established. Abnormal formation of blood vessels results in embryonic lethality and also contributes to the pathogenesis of a number of human diseases, including cancer metastasis. To understand the molecular events associated with blood vessel formation, we established a fluorescence staining-based protocol on mouse embryonic skin. We harvested mouse embryonic skin and performed whole-mount staining. The reconstructed three-dimensional vascular structure provided detailed information on angiogenesis.

Salicylic acid is a phenolic phytohormone which controls plant growth and development. A methyl ester (MSA) derivative thereof is volatile and involved in plant-insect or plant-plant communication. Here we show that the nematode-trapping fungus Duddingtonia flagrans uses a methyl-salicylic acid isomer, 6-MSA as morphogen for spatiotemporal control of trap formation and as chemoattractant to lure Caenorhabditis elegans into fungal colonies. 6-MSA is the product of a polyketide synthase and an intermediate in the biosynthesis of arthrosporols. The polyketide synthase (ArtA), produces 6-MSA in hyphal tips, and is uncoupled from other enzymes required for the conversion of 6-MSA to arthrosporols, which are produced in older hyphae. 6-MSA and arthrosporols both block trap formation. The presence of nematodes inhibits 6-MSA and arthrosporol biosyntheses and thereby enables trap formation. 6-MSA and arthrosporols are thus morphogens with some functions similar to quorum-sensing molecules. We show that 6-MSA is important in interkingdom communication between fungi and nematodes., Methyl salicylate ester is a plant metabolite involved in plant-insect and plant-plant interactions. Here, Yu et al. show that a nematode-trapping fungus has potential to produce a related compound, 6-methyl salicylate, which attracts its prey (nematodes) and modulates spore germination and trap formation in the fungus.

The Cydia pomonella granulovirus (CpGV) has been used as a biological control agent of codling moth (Cydia pomonella), a severe global pest on pome fruit. Despite the economic importance, our knowledge of its molecular biology is still limited and a detailed picture of its gene expression is still missing. Here, we sequenced the transcriptome of codling moth larvae infected with the Mexican isolate CpGV-M and analyzed the expression of viral genes at 12, 48, and 96 h post infection (hpi). The results showed that two genes (p6.9 and pp31/39K) related to DNA binding of virus production, were highly expressed at 48 and 96 hpi. From 48 to 96 hpi, the expression of genes associated with virus replication and dissemination decreased, whereas the expression of genes related to infectious virion production and per os infectivity increased. This study provides a comprehensive view of CpGV gene expression patterns in host larvae.

Symbiotic microorganisms in invertebrates play vital roles in host ecology and evolution. Cardinium, a common intracellular symbiont, is transinfected into the important agricultural pest Nilaparvata lugens (rice brown planthopper) to regulate its reproduction, but how this impacts its microbial community is unknown. Here, we characterized the bacterial microbiota from N. lugens, with or without Cardinium, at different developmental stages and in various adult tissues using 16S ribosomal ribonucleic acid (16S rRNA) gene sequencing. Upon infection with Cardinium, we found that microbial diversity in the different developmental stages of N. lugens (especially females), and in female midguts and male testes, was lower than that in the uninfected control. There was a negative correlation between Cardinium and most related genera and between Bacteroidetes and Proteobacteria. Although the microbial structure varied during Cardinium infection, Acinetobacter spp. were a core microbiome genus. The Cardinium infection enhanced the relative density of midgut-associated Acinetobacter spp., with both bacteria exhibiting tissue-specific tropism. In addition, this infection caused the changes of main microbial functions in N. lugens. These results offer insights into the effects of alien (i.e. newly introduced from other organism) Cardinium infection on N. lugens-associated microbiotas, aiding in the development of transinfected endosymbionts for pest control.

Application of plant growth regulators (PGRs) is a novel strategy for allay of the adverse effects caused by biotic/abiotic stresses. However, no studies have vividly executed mathematic evaluation for the assessment of various PGRs on root phenotype traits (RPTs) against pollutants. In the present study, a microcosm hydroponic experiment was conducted to examine responses of RPTs under SCN− (0, 24, 96, and 300 mg SCN/L) stress in the presence of PGRs such as jasmonic acid (JA), indole-3-acetic acid (IAA), and sodium hydrosulfide (NaHS) in rice plants. Fuzzy synthetic evaluation was applied to determine the outcome of the effects of various PGRs on the RPTs under SCN− exposure. Root scanning results indicated that exogenous IAA and NaHS has the greater potential for improving the RPTs of rice seedlings under SCN− stress, while JA failed to uplift the RPTs in response to SCN− stress. Fuzzy synthetic evaluation indicated that in control plants (without SCN−), the effect of three PGRs applied on the RPTs is as follows: NaHS > IAA > JA. At 24 mg SCN/L, NaHS and IAA had consistent actuate in regulating RPTs of rice seedlings, while all PGRs amended have an affirmative impact on RPTs at 96 and 300 mg SCN/L. The present research highlights the utilization of contemporary mathematic method to screen the superior species of PGRs through the RPTs test of plants under pollutant belt.

During embryonic cortical development, radial glial cells (RGCs) are the major source of neurons, and these also serve as a supportive scaffold to guide neuronal migration. Similar to Vimentin, glial fibrillary acidic protein (GFAP) is one of the major intermediate filament proteins present in glial cells. Previous studies confirmed that prenatal ethanol exposure (PEE) significantly affected the levels of GFAP and increased the disassembly of radial glial fibers. GFAPδ is a variant of GFAP that is specifically expressed in RGCs; however, to the best of our knowledge, there are no reports regarding how PEE influences its expression during cortical development. In the present study, the effects of PEE on the expression and distribution of GFAPδ during early cortical development were assessed. It was found that PEE significantly decreased the expression levels of GFAP and GFAPδ. Using double immunostaining, GFAPδ was identified to be specifically expressed in apical and basal RGCs, and was co‑localized with other intermediate filament proteins, such as GFAP, Nestin and Vimentin. Additionally, PEE significantly affected the morphology of radial glial fibers and altered the behavior of RGCs. The loss of GFAPδ accelerated the transformation of RGCs into astrocytes. Using co‑immunostaining with Ki67 or phospho‑histone H3, GFAPδ+ cells were observed to be proliferative or mitotic cells, and ethanol treatment significantly decreased the proliferative or mitotic activities of GFAPδ+ RGCs. Taken together, the results suggested that PEE altered the expression patterns of GFAPδ and impaired the development of radial glial fibers and RGC behavior. The results of the present study provided evidence that GFAPδ may be a promising target to rescue the damage induced by PEE.