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Delimiting species requires multiple sources of evidence. Here, we delimited two varieties of Halenia elliptica (Gentianaceae) using several lines of evidence, including morphological traits and mating system in a sympatric population, phylogenetic relationships based on nrITS and cpDNA (rpl16) data, and complete chloroplast genome sequences. Comparative analysis of 21 morphological traits clearly separates the two varieties of H. elliptica. Examination of the flowering process and pollination treatments indicate that H. elliptica var. grandiflora produces seeds via outcrossing, whereas H. elliptica var. elliptica produces seeds via mixed mating. Furthermore, hand-pollinated hybridization of the two varieties produced no seeds. Observations of pollinators showed that when bees began a pollination bout on H. elliptica var. grandiflora they preferred to continue pollinating this variety; however, when they began a pollination bout on H. elliptica var. elliptica, they showed no preference for either variety. Phylogenetic analysis confirmed the monophyly of H. elliptica, which was further divided into two monophyletic clades corresponding to the two varieties. A large number of variants from the chloroplast genomes reflected remarkable genetic dissimilarities between the two varieties of H. elliptica. We recommend that the two varieties of H. elliptica should be revised as two species (H. elliptica and Halenia grandiflora). Our findings indicate that H. elliptica varieties may have split into two separate species due to a shift in mating system, changes in flowering phenology and/or post-pollination reproductive isolation.

Carbapenemase-producing Enterobacteriaceae (CPE) isolates are recognized as one of the most severe threats to public health. However, the population structure and genetic characteristics of CPE isolates among bloodstream infections (BSIs) are largely unknown. To address this knowledge gap, in this study, we included patients with clinically significant BSIs due to Enterobacterales isolates, recruited from 26 sentinel hospitals in China (2014–2015). CPE isolates were microbiologically and genomically characterized, including their susceptibility profiles, molecular typing, phylogenetic features, and genetic context analysis of carbapenemase-encoding genes. Of the 2569 BSI Enterobacterales isolates enrolled, 42 (1.6%) were carbapenemase-positive. Moreover, among the 2242 investigated isolates, 1111 (49.6%) extended-spectrum β-lactamase (ESBL)-producing isolates were identified in Escherichia (E.) coli, Klebsiella (K.) pneumoniae, Proteus (P.) mirabilis, and K. oxytoca. Whole genome sequencing analysis showed the clonal spread of K. pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae sequence type 11 (ST11) and New Delhi metallo-β-lactamase (NDM)-5-producing E. coli ST167 in our collection. Plasmid analysis revealed that carbapenemase-encoding genes were located on multiple plasmids. A high prevalence of biofilm-encoding type 3 fimbriae clusters and yesiniabactin-associated genes was observed in K. pneumoniae isolates. This work demonstrates the high prevalence of ESBLs and the wide dissemination of CPE among BSI isolates in China, which represent real clinical threats. Moreover, our findings first illustrate a more comprehensive genome scenario of CPE isolates among BSIs. The clonal spread of KPC-2-producing K. pneumoniae ST11 and NDM-5-producing E. coli ST167 needs to be closely monitored.

Stripe rust, caused by Puccinia striiformis f. sp. tritici, is a damaging disease of wheat globally, and breeding resistant cultivars is the best control strategy. The Chinese winter wheat cultivar Shumai126 (SM126) exhibited strong resistance to P. striiformis f. sp. tritici in the field for more than 10 years. The objective of this study was to identify and map quantitative trait loci (QTL) for resistance to stripe rust in a population of 154 recombinant inbred lines (RILs) derived from a cross between cultivars Taichang29 (TC29) and SM126. The RILs were tested in six field environments with a mixture of the Chinese prevalent races (CYR32, CYR33, CYR34, Zhong4, and HY46) of P. striiformis f. sp. tritici and in growth chamber with race CYR34 and genotyped using the Wheat55K single nucleotide polymorphism (SNP) array. Six QTL were mapped on chromosomes 1BL, 2AS, 2AL, 6AS, 6BS, and 7BL, respectively. All QTL were contributed by SM126 except QYr.sicau-2AL. The QYr.sicau-1BL and QYr.sicau-2AS had major effects, explaining 27.00 to 39.91% and 11.89 to 17.11% of phenotypic variances, which may correspond to known resistance genes Yr29 and Yr69, respectively. The QYr.sicau-2AL, QYr.sicau-6AS, and QYr.sicau-6BS with minor effects are likely novel. QYr.sicau-7BL was only detected based on growth chamber seedling data. Additive effects were detected for the combination of QYr.sicau-1BL, QYr.sicau-2AS, and QYr.sicau-2AL. SNP markers linked to QYr.sicau-1BL (AX-111056129 and AX-108839316) and QYr.sicau-2AS (AX-111557864 and AX-110433540) were converted to breeder-friendly Kompetitive allele-specific PCR (KASP) markers that would facilitate the deployment of stripe rust resistance genes in wheat breeding.

Circular RNAs (circRNAs) are a group of covalently closed RNAs, and their biological function is largely unknown. In this study, we focused on circRNAs that are generated from exon back-splicing (exonic circRNAs). The linear RNA counterparts encode functional proteins so that we can compare and investigate the relationship between circular and linear RNAs. We compared circRNA expression profiles between untreated and Pseudomonas syringae-infected Arabidopsis and identified and experimentally validated differentially expressed exonic circRNAs by multiple approaches. We found that exonic circRNAs are preferentially enriched in biological processes that associate with biotic and abiotic stress responses. We discovered that circR194 and circR4022 are involved in plant response against P. syringae infection, whereas circR11208 is involved in response against Botrytis cinerea infection. Intriguingly, our results indicate that these exonic circRNAs function synergistically with their corresponding linear RNAs. Furthermore, circR4022 and circR11208 also play substantial roles in Arabidopsis tolerance to salt stress. This study extends our understanding of the molecular functions of plant circRNAs.

Ciprofloxacin (CIP) is an antibiotic used to treat infections caused by bacteria. In this experiment, key enzymes and intracellular metabolites of Lactobacillus plantarum DNZ-4 was researched under CIP stress. The results showed that the activities of hexokinase, pyruvate kinase, β-galactosidase and Na+, K+-ATPase after 1/2 minimum bacteriostatic concentration (MIC) CIP treatment were significantly decreased (P

Early diagnosis of bacterial infection and tracking of treatment effect are of great importance for developing a “sense-and-treat” integrated system. Herein, we developed a bacteria-triggered, portable, wearable and colorimetric film-based band-aid (FBA) for closed-loop monitoring and light-controlled therapy of wound infection. FBA with high photothermal conversion efficiency of 52.56% was prepared by wrapping Bi2S3 nanoflowers (BS NFs) loaded with rhodium nanoparticles (Rh NPs) and bromothymol blue (BTB) into LB agar film, integrating bacteria-triggered color change, photothermal/photodynamic therapy (PTT/PDT) synergistic bactericidal therapy and agar-based band aid in one intelligent system. Initially, FBA effectively simulates the pH sensing mechanism, and monitors the occurrence of bacterial infections within 5 minutes through color changes of Staphylococcus aureus (S. aureus) from blue to yellow and Escherichia coli (E. coli) from yellow to blue. Additionally, the short-term and controlled antibacterial strategy of “one light dual-mode responses” (photothermal and photodynamic responses) was implemented with the introduce of near-infrared (NIR). Ultimately, the effectiveness of FBA was fully validated in the monitoring and treating of S. aureus-infected mouse wounds. Notably, the designed FBA decisively abandoned off-target side effects maximizing the treatment effect and nakedly tracking therapeutic situation in real time, contributing an effective antibacterial alternative strategy for reducing the use of antibiotics. To the best of our knowledge, such integrated system is still unreported on film-fixed model. In view of the advantages of the low cost and convenience of the simple device, the integrated design is expected to provide a solution for the development of a closed-loop biomedical system combining diagnosis and treatment.

Xanthomonas oryzae pv. oryzae is the causal agent of bacterial blight, one of the most devastating diseases of rice. Here, a hypervirulent strain, C9-3, defeating Xa1, Xa10, xa13, and Xa23 resistance genes, was used to extract genomic DNA for single molecule real-time (SMRT) sequencing. After assembly, the genome consists of a single-circular chromosome with the size of 4,924,298 bp with G+C content of 63.7% and contains 4,715 genes. Annotation and analysis of the TALE genes using a suite of applications named AnnoTALE suggested that 17 transcription activator-like effectors, including 15 typical TALEs and 2 iTALEs/truncTALEs, were encoded in the genome. The approach and genome resource will contribute to the discovery of new virulence effectors and understanding on rice-X. oryzae pv. oryzae interactions.

Soil inorganic phosphate (Pi) levels are frequently suboptimal for the growth and development of crop plants. Although MADS-box genes participate in diverse plant developmental processes, their involvement in phosphate starvation responses (PSRs) remains unclear. We identified a type I MADS-box transcription factor gene, TaMADS2-3D, which was rapidly induced under low-Pi stress in roots of wheat (Triticum aestivum). A TaMADS2-3D-GFP fusion protein was found located in the nucleus. Transgenic Arabidopsis plants overexpressing TaMADS2-3D (TaMADS2-3DOE) showed shortened primary roots, increased lateral root density, and retarded seedling growth under high-Pi (HP) conditions, accompanied by increased Pi contents in their shoots and roots. The Arabidopsis TaMADS2-3DOE plants showed similar PSR phenotypes under low Pi (LP) conditions. These results indicate constitutive activation of PSRs by overexpression of TaMADS2-3D in Arabidopsis. Reactive oxygen species (ROS), H2O2 and O2−, levels were increased in root tips of Arabidopsis TaMADS2-3DOE plants under HP conditions. Transcriptome analysis of Arabidopsis TaMADS2-3DOE plants under different Pi regimes revealed expression changes for a variety of PSR genes including AtZAT6. Overexpression of TaMADS2-3D in wheat also led to constitutive activation of PSRs. We propose that TaMADS2-3D regulates plant PSRs probably by modulating ROS homeostasis, root development, PSR gene expression, and Pi uptake. This study increases our understanding of plant PSR regulation and provides a valuable gene for improving phosphorus-use efficiency in wheat and other crops.

Glioblastoma (GBM) is the most lethal primary brain cancer characterized by therapeutic resistance, which is promoted by GBM stem cells (GSC). Here, we interrogated gene expression and whole-genome CRISPR/Cas9 screening in a large panel of patient-derived GSCs, differentiated GBM cells (DGC), and neural stem cells (NSC) to identify master regulators of GSC stemness, revealing an essential transcription state with increased RNA polymerase II–mediated transcription. The YY1 and transcriptional CDK9 complex was essential for GSC survival and maintenance in vitro and in vivo. YY1 interacted with CDK9 to regulate transcription elongation in GSCs. Genetic or pharmacologic targeting of the YY1–CDK9 complex elicited RNA m6A modification–dependent interferon responses, reduced regulatory T-cell infiltration, and augmented efficacy of immune checkpoint therapy in GBM. Collectively, these results suggest that YY1–CDK9 transcription elongation complex defines a targetable cell state with active transcription, suppressed interferon responses, and immunotherapy resistance in GBM. Significance: Effective strategies to rewire immunosuppressive microenvironment and enhance immunotherapy response are still lacking in GBM. YY1-driven transcriptional elongation machinery represents a druggable target to activate interferon response and enhance anti–PD-1 response through regulating the m6A modification program, linking epigenetic regulation to immunomodulatory function in GBM. This article is highlighted in the In This Issue feature, p. 275

Huntington's disease (HD) is a devastating, autosomal dominant neurodegenerative disease caused by a trinucleotide repeat expansion in the huntingtin (HTT) gene. Inactivation of the mutant allele by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 based gene editing offers a possible therapeutic approach for this disease, but permanent disruption of normal HTT function might compromise adult neuronal function. Here, we use a novel HD mouse model to examine allele-specific editing of mutant HTT (mHTT), with a BAC97 transgene expressing mHTT and a YAC18 transgene expressing normal HTT. We achieve allele-specific inactivation of HTT by targeting a protein coding sequence containing a common, heterozygous single nucleotide polymorphism (SNP). The outcome is a marked and allele-selective reduction of mHTT protein in a mouse model of HD. Expression of a single CRISPR-Cas9 nuclease in neurons generated a high frequency of mutations in the targeted HD allele that included both small insertion/deletion (InDel) mutations and viral vector insertions. Thus, allele-specific targeting of InDel and insertion mutations to heterozygous coding region SNPs provides a feasible approach to inactivate autosomal dominant mutations that cause genetic disease.

A couple diagnosed as carriers for lamellar ichthyosis, an autosomal recessive rare disease, encountered two pregnancy losses. Their blood samples showed the same heterozygous c.607C>T mutation in the TGM1 gene. However, we found that about 98.4% of the sperm had mutations, suggesting possible de novo germline mutation. To explore the probability of correcting this mutation, we used two different adenine base editors (ABEs) combined with related truncated single guide RNA (sgRNA) to repair the pathogenic mutation in mutant zygotes. Our results showed that the editing efficiency was 73.8% for ABEmax-NG combined with 20-bp-length sgRNA and 78.7% for Sc-ABEmax combined with 19-bp-length sgRNA. The whole-genome sequencing (WGS) and deep sequencing analysis demonstrated precise DNA editing. This study reveals the possibility of correcting the genetic mutation in embryos with the ABE system.

Objectives We aimed to compare the efficiency of the CapitalBioMycobacterium real-time polymerase chain reaction (PCR) detection test with the standard Xpert MTB/RIF assay for the diagnosis of tuberculous meningitis (TBM). Methods We analyzed cerebrospinal fluid (CSF) from 163 patients with suspected TBM that were collected between January 1, 2018, and December 31, 2019. For both tests, we determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC). Next, we compared the diagnostic accuracy of the two techniques using clinical diagnosis as a reference standard. Results The sensitivity, specificity, PPV, NPV, and AUC, of the CapitalBio Mycobacterium detection test were 48.5%, 100%, 100%, 29.6%, and 0.74, respectively, when used for the diagnosis of TBM. In comparison, the Xpert MTB/RIF assay returned values of 47.0%, 100%, 100%, 29.0%, and 0.74, respectively. Our analysis showed that the diagnostic accuracies of the CapitalBio Mycobacterium detection test and the Xpert MTB/RIF assay were very similar; the accuracy of both tests for detecting mycobacteria was significantly higher than that associated with acid­fast staining. Conclusions The CapitalBio Mycobacterium real-time PCR detection test has moderate sensitivity and very high specificity for TBM; results are very similar to those generated by the Xpert MTB/RIF assay. We recommend that the CapitalBio PCR test should be used as an initial screening method for TB.

Kazak artisanal cheese is a traditionally fermented food from the Uighur Autonomy Region of Xinjiang, China. In this study, we used Illumina MiSeq high-throughput sequencing technology to explore the microbial diversity during the milk fermentation of Kazak traditional hand-fermented cheese in Xinjiang, by analyzing the V3–V4 variable region of the bacterial 16S rRNA gene. Results showed that Lactobacillus and Lactococcus from the Firmicutes group comprised the dominant genera. Lactobacillus, Lactococcus, Acinetobacter, Anoxybacillus, Macrococcus, Acetobacter, Kurthia, Lelliottia, and Leuconostoc were identified as the key microbial groups during the milk fermentation of cheese. Correlation analysis also indicated that Lactobacillus had strong negative connections with Lactococcus, Acinetobacter, Macrococcus, Anoxybacillus, and Staphylococcus. The genera of Lactobacillus and Lactococcus (e.g., Lactobacillus paracasei B1, Lactobacillus sp. B4 and Lactococcus lactis B11) had higher enzyme activity characteristics according to the enzyme activity experiments. Subsequent gene function prediction indicated that the microorganisms in fermented milk products mainly contributed to carbohydrate and amino acid metabolism, which might be closely related to the development of the flavor of the cheese. Our study provides a theoretical basis for understanding the succession of bacteria and the application of potential functional microorganisms in Kazak cheese.

Vascular smooth muscle cell (VSMC) hyperplasia is closely associated with AS progression. Hence, it is of great significance to elucidate the molecular mechanisms underlying the involvement of VSMCs in AS. SHH antagonist can inhibit the excessive proliferation, migration and phenotypic transformation of PDGF-BB-induced VSMCs. It has been proved that CUL3 can suppress Hedgehog signaling. This current work was designed to identify the biological role of CUL3 in the behaviors of VSMCs in AS and investigate the potential molecular mechanism. VSMCs were treated with PDGF-BB to establish the cell model in vitro. Levels of CUL3, SHH and Gli1 in PDGF-BB-stimulated VSMCs were measured by RT-qPCR analysis. Then, the precise functions of CUL3 in VSMCs were determined from the perspectives of proliferation, migration, apoptosis and phenotype transformation. Besides, the influence of CUL3 on inflammatory response in VSMCs was evaluated. Moreover, the impact of CUL3 on Hedgehog signaling pathway was also investigated. In the present research, it was observed that CUL3 was lowly expressed and SHH and Gli1 were highly expressed in PDGF-BB-stimulated VSMCs. Upregulation of CUL3 suppressed the excessive proliferation, migration and phenotypic transformation and facilitated the apoptosis of PDGF-BB-stimulated VSMCs. In addition, elevation of CUL3 alleviated inflammatory response in PDGF-BB-stimulated VSMCs. Importantly, CUL3 overexpression inactivated Hedgehog signaling pathway. To conclude, CUL3 might regulate the biological behaviors of VSMCs in AS by modulating Hedgehog signaling pathway. These data encourage to further investigate any potential therapeutic role of CUL3 in animal models of AS and explore therapeutic values for AS clinically.

The study aimed to evaluate the effects of Allium mongolicum Regel (AMR) and its water‐ and fat‐soluble extracts on the quality of fermented mutton sausages. Sausages were produced with mutton and fat. Four treatments: CO, without Allium mongolicum Regel and its extracts, used as control; AMR with Allium mongolicum Regel; AWE with water‐soluble extract of Allium mongolicum Regel; and AFE with liposoluble extract from Allium mongolicum Regel, were produced and analyzed for pH, water activity (aw), free amino acids, fatty acids, and volatiles were, respectively, in fermented mutton sausages during processing (0, 2, 5, and 7 days). The results showed that the pH values of the liposoluble extract from Allium mongolicum Regel (AFE), respectively, are lower than that of sample CO at the end of fermentation and ripening. The aw in all group of sausages significantly dropped to 0.88 at the end of ripening (Day 7). Adding Allium mongolicum Regel and its water‐soluble extract can improve the serine (SER) content of fermented mutton sausage. The contents of five essential amino acids (EAA) were added when adding Allium mongolicum Regel and its fat‐soluble extract. The total fatty acid (TFA) in the treatments increased during drying and ripening. The addition of Allium mongolicum Regel and its extract can increase the content of volatile flavor substances such as 3‐hydroxy‐2‐butanone, 3‐methylbutyraldehyde, hexanal, octanal, and nonanal at the later stage of maturity, so as to improve the flavor substances in fermented mutton sausage. Water‐soluble extract of Allium mongolicum Regel (AWE) and AFE treatments had more intense flavor at the end of ripening (Day 7). The flavor of fermented mutton sausage can be improved by adding Allium mongolicum Regel and its extracts into fermented mutton sausage.

Background Skeletal muscle regeneration is an adaptive response to injury that is crucial to the maintenance of muscle mass and function. A p21‐activated kinase 4 (PAK4) serine/threonine kinase is critical to the regulation of cytoskeletal changes, cell proliferation, and growth. However, PAK4's role in myoblast differentiation and regenerative myogenesis remains to be determined. Methods We used a mouse model of myotoxin (notexin)‐induced muscle regeneration. In vitro myogenesis was performed in the C2C12 myoblast cell line, primary myoblasts, and primary satellite cells. In vivo overexpression of PAK4 or kinase‐inactive mutant PAK4S474A was conducted in skeletal muscle to examine PAK4's kinase‐dependent effect on muscle regeneration. The regeneration process was evaluated by determining the number and size of multinucleated myofibres and expression patterns of myogenin and eMyHC. To explore whether PAK4 inhibition improves muscle regeneration, mice were injected intramuscularly with siRNA that targeted PAK4 or orally administered with a chemical inhibitor of PAK4. Results p21‐activated kinase 4 was highly expressed during the myoblast stage, but expression gradually and substantially decreased as myoblasts differentiated into myotubes. PAK4 overexpression, but not kinase‐inactive mutant PAK4S474A overexpression, significantly impeded myoblast fusion and MyHC‐positive myotube formation in C2C12 cells, primary myoblasts, and satellite cells (P

BACKGROUND Excessive nitrogen (N) fertilization in glasshouse fields greatly increases N loss and fossil-fuel energy consumption resulting in serious environmental risks. Microbial inoculants are strongly emerging as potential alternatives to agrochemicals and offer an eco-friendly fertilization strategy to reduce our dependence on synthetic chemical fertilizers. Effects of a N-fixing strain Pseudomonas protegens CHA0-ΔretS-nif on ginger plant growth, yield, and nutrient uptake, and on earthworm biomass and the microbial community were investigated in glasshouse fields in Shandong Province, northern China. RESULTS Application of CHA0-ΔretS-nif could promote ginger plant development, and significantly increased rhizome yields, by 12.93% and 7.09%, respectively, when compared to uninoculated plants and plants treated with the wild-type bacterial strain. Inoculation of CHA0-ΔretS-nif had little impact on plant phosphorus (P) acquisition, whereas it was associated with enhanced N and potassium (K) acquisition by ginger plants. Moreover, inoculation of CHA0-ΔretS-nif had positive effects on the bacteria population size and the number of earthworms in the rhizosphere. Similar enhanced performances were also found in CHA0-ΔretS-nif-inoculated ginger plants even when the N-fertilizer application rate was reduced by 15%. A chemical N input of 573.8 kg ha-1 with a ginger rhizome yield of 1.31 × 105 kg ha-1 was feasible. CONCLUSIONS The combined application of CHA0-ΔretS-nif and a reduced level of N-fertilizers can be employed in glasshouse ginger production for the purpose of achieving high yields while at the same time reducing the inorganic-N pollution from traditional farming practices. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Both DNA damage response and methylation play a crucial role in antigen receptor recombination by creating a diverse repertoire in developing lymphocytes, but how their defects relate to T cell repertoire and phenotypic heterogeneity of immunodeficiency remains obscure. We studied the TCR repertoire in patients with the mutation in different genes (ATM, DNMT3B,ZBTB24,RAG1,DCLRE1C, andJAK3) and uncovered distinct characteristics of repertoire diversity. We propose that early aberrancies in thymus T cell development predispose to the heterogeneous phenotypes of the immunodeficiency spectrum. Shorter CDR3 lengths in ATM-deficient patients, resulting from a decreased number of nucleotide insertions during VDJ recombination in the pre-selected TCR repertoire, as well as the increment of CDR3 tyrosine residues, lead to the enrichment of pathology-associated TCRs, which may contribute to the phenotypes of ATM deficiency. Furthermore, patients withDNMT3BandZBTB24mutations who exhibit discrepant phenotypes present longer CDR3 lengths and reduced number of known pathology-associated TCRs.

Efficient in vitro callus generation is required for tissue culture propagation, a process that allows for plant regeneration and transgenic breeding for desired phenotypes. Identifying genes and regulatory elements that prevent impaired callus growth and callus browning is essential for the development of in vitro callus systems. Here, we show that the BREVIPEDICELLUS and ERECTA pathways in Arabidopsis calli converge to prevent callus browning, and positively regulate the expression of the isoperoxidase gene AtPRX17 in rapidly growing calli. Loss-of-function mutations in both BREVIPEDICELLUS and ERECTA resulted in markedly increased callus browning. Transgenic lines expressing 35S pro::AtPRX17 in the bp-5 er105 double mutant background fully rescued this phenotypic abnormality. Using in vivo (chromatin immunoprecipitation-PCR and transient expression) and in vitro (electrophoretic mobility shift assays) assays, we observed that the BREVIPEDICELLUS protein binds directly to the upstream sequence of AtPRX17 to promote its transcription during callus growth. ERECTA is a ubiquitous factor required for cell proliferation and growth. We show that ERECTA positively regulates the expression of the transcription factor WRKY6, which directly binds to a separate site on the AtPRX17 promoter, further increasing its expression. Our data reveal an important molecular mechanism involved in the regulation of peroxidase isozyme expression to reduce Arabidopsis callus browning.

Background Epicutaneous sensitization is an important route for the production of IgE, and skin inflammation-induced IgE has recently been reported having features of natural antibody. Atopic dermatitis (AD) and psoriasis have differentially increased level of serum IgE; however, the production mechanism of IgE in these inflammatory skin diseases remains unknown. Objective To explore the origin of IgE in AD and psoriasis by analyzing the B cell receptor repertoire. Methods mRNA was prepared from peripheral blood mononuclear cells of AD and psoriasis patients that had elevated serum levels of IgE, and immunoglobulin heavy chain (IGH) repertoires were sequenced after reverse transcription. Clonal lineages of B cells containing members expressing IgE were identified, and somatic hypermutations in IGH inherited from common ancestors within the clonal lineage were used to infer the relationships between B cells. Results The proportions of IGHE from AD and psoriasis were higher than that of normal control, which were positively correlated with the levels of serum total IgE. The somatic hypermutation value of IGHE variable region was lower than that of IGHG and IGHA, but higher than IGHM and IGHD, indicating a mixed natural and adaptive origins of IgE; and psoriasis demonstrated lower level of hypermutation than AD. The Shannon indexes of CDR3 in IGHE of AD and psoriasis were higher than that of normal control, also supporting the natural origin. The VH usage of IgE was weakly biased in AD and psoriasis patients with high level of house dust mite-specific IgE. Comparison of the number of shared mutations in multi-isotype lineages containing IgE showed that isotype-switching from IgG-expressing B cells might be the major source of IgE in AD and psoriasis. Conclusion IgE has heterogeneous origin in AD and psoriasis, and skin inflammation may contribute to the increased production of natural IgE.

Background Recurrent spontaneous abortion (RSA) is one of the common complication of pregnancy, bringing heavy burden to the patients and their families. The study aimed to explore the lncRNA-miRNA-mRNA network associated with recurrent spontaneous abortion. Methods By transcriptome sequencing, we detected differences in lncRNA, miRNA and mRNA expression in villus tissue samples collected from 3 patients with RSA and 3 normal abortion patients. Differentially expressed lncRNAs, miRNAs and genes (DELs, DEMs and DEGs, respectively) were identified, and Geno Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to determine the functions of DELs and DEGs, which were analysed by Fisher’s test. We also observed the regulatory relationships between miRNA-mRNA and lncRNA-miRNA by Cytoscape 3.6.1. Results The results showed that 1008 DELs (523 upregulated and 485 downregulated), 475 DEGs (201 upregulated and 274 downregulated) and 37 DEMs (15 upregulated and 22 downregulated) were identified. And we also constructed a novel lncRNA-related ceRNA network containing 31 lncRNAs, 1 miRNA (hsa-miR-210-5p) and 3 genes (NTNG2, GRIA1 and AQP1). Conclusions lncRNA-related ceRNA network containing 31 lncRNAs, 1 miRNA (hsa-miR-210-5p) and 3 mRNAs (NTNG2, GRIA1 and AQP1) was constructed. The results may provide a basic theory for elucidating the mechanism underlying RSA.

Background Lignocellulosic biomass is an attractive and sustainable alternative to petroleum-based feedstock for the production of a range of biochemicals, and pretreatment is generally regarded as indispensable for its biorefinery. However, various inhibitors that severely hinder the growth and fermentation of microorganisms are inevitably produced during the pretreatment of lignocellulose. Presently, there are few reports on a single microorganism that can detoxify or tolerate toxic mixtures of pretreated lignocellulose hydrolysate while effectively transforming sugar components into valuable compounds. Alternatively, microbial coculture provides a simpler and more efficacious way to realize this goal by distributing metabolic functions among different specialized strains. Results In this study, a novel synthetic microbial consortium, which is composed of a responsible for detoxification bacterium engineered Pseudomonas putida KT2440 and a lactic acid production specialist Bacillus coagulans NL01, was developed to directly produce lactic acid from highly toxic lignocellulosic hydrolysate. The engineered P. putida with deletion of the sugar metabolism pathway was unable to consume the major fermentable sugars of lignocellulosic hydrolysate but exhibited great tolerance to 10 g/L sodium acetate, 5 g/L levulinic acid, 10 mM furfural and HMF as well as 2 g/L monophenol compound. In addition, the engineered strain rapidly removed diverse inhibitors of real hydrolysate. The degradation rate of organic acids (acetate, levulinic acid) and the conversion rate of furan aldehyde were both 100%, and the removal rate of most monoaromatic compounds remained at approximately 90%. With detoxification using engineered P. putida for 24 h, the 30% (v/v) hydrolysate was fermented to 35.8 g/L lactic acid by B. coagulans with a lactic acid yield of 0.8 g/g total sugars. Compared with that of the single culture of B. coagulans without lactic acid production, the fermentation performance of microbial coculture was significantly improved. Conclusions The microbial coculture system constructed in this study demonstrated the strong potential of the process for the biosynthesis of valuable products from lignocellulosic hydrolysates containing high concentrations of complex inhibitors by specifically recruiting consortia of robust microorganisms with desirable characteristics and also provided a feasible and attractive method for the bioconversion of lignocellulosic biomass to other value-added biochemicals.

Societal Impact Statement A future with a secure and safe food supply requires humanity to preserve and exploit the vast variation available across agricultural plant species. Apples are one of the most widely consumed fruits and provide significant nutritional value worldwide. Here, we characterize key agricultural traits in a diverse collection of apples to provide a foundation for future apple improvement. We show that commercially successful apple varieties capture only a small fraction of apple diversity, and demonstrate that significant improvement is possible by tapping into existing genetic diversity. Summary ●Here we present a comprehensive evaluation of apple diversity through phenotyping of Canada's Apple Biodiversity Collection (ABC) which contains over 1000 apple accessions. ●We assessed, over a 4‐year period, more than 20,000 individual apples and quantified variation across 39 phenotypes, including phenology and fruit quality both at harvest and after 3 months of cold storage. ●We observe that apples in the ABC display a wide range of phenotypic variation that may prove useful for future apple improvement. For example, apples can differ by nearly 61‐fold in weight, 18‐fold in acidity, and 100‐fold in phenolic content. We quantified the dramatic changes to apple physiology that occur during 3 months of cold storage: on average, apples lost 39% of their firmness, 31% of their acidity, and 9% of their weight, but gained 7% in soluble solids. Harvest date, flowering date, and time to ripen were all positively correlated with firmness, which suggests that the developmental pathways that drive phenological events throughout the growing season may play a role in determining an apple's texture. Finally, we show that apple breeding has selected for a significant decline in phenolic content over the past 200 years: apple cultivars released after 1940 had a 30% lower median phenolic content than cultivars released before 1940. ●The data and analyses presented here not only provide a comprehensive quantification of the range across, and relationships among diverse apple phenotypes, but they also enable genetic mapping studies that will provide the foundation for future apple improvement via genomics‐assisted breeding.

Oesophageal squamous cell carcinoma (OSCC) is a prevalent malignancy with high morbidity and mortality as a result of early metastasis and poor prognosis. Metastasis is a multistep process, involving various signalling pathways. Circular RNAs (circRNAs) are a class of covalently closed noncoding RNAs, the aberrant expression of which is reported to be involved in several biological events, including cell transformation, proliferation, migration, invasion, apoptosis and metastasis. Several studies have reported interactions between circRNAs and metastasis‐associated signalling pathways. The abundance, stability and highly specific expression of candidate circRNAs make them potential biomarkers and therapeutic targets in OSCC. In this review article, we comprehensively describe metastasis‐related circRNAs and their interactions with epithelial–mesenchymal transition‐associated molecules. We also describe the molecular mechanisms and clinical relevance of circRNAs in OSCC progression and metastasis., The aberrant expression of circular RNAs (circRNAs) is reported to be involved in several biological events, including proliferation, cell cycle, apoptosis and metastasis. In this review article, we comprehensively describe metastasis‐related circRNAs and their interactions with epithelial–mesenchymal transition‐associated molecules, as well as the molecular mechanisms and clinical relevance of circRNAs in oesophageal squamous cell carcinoma progression and metastasis.

In this work, Manganese ferrite nanoparticles (MnFe 2O4 NPs) were synthesized, and their potential to increase the biohydrogen (bio-H2) yield of glucose in mesophilic and thermophilic fermentations was evaluated. Material characterization showed that the MnFe 2O4 NPs were perfectly synthesized, with a specific surface area of 43.97 m2g−1. Both mesophilic and thermophilic fermentation obtained the highest bio-H2 yields of 272.7 and 183.4 mL H2/g glucose in the 400 mg/L MnFe 2O4 NPs group, which values were increased by 40.1% and 131.9% (37 °C and 55 °C), respectively, compared to their control groups. Soluble microbial products (SMPs) showed that MnFe 2O4 NPs enhanced the butyrate pathway. Three-dimensional fluorescence spectroscopy analysis showed that MnFe 2O4 NPs increased the extracellular polymer content of anaerobic sludge. The results showed that MnFe 2O4 NPs distinctly increased the abundance of Clostridium_sensu_stricto 1 (39.49%) in the microbial community during mesophilic fermentation and improved the abundance of the dominant bacteria Clostridium_sensu_stricto_7 (25.59%) and Longlinea (21.36%) during thermophilic fermentation. Real-time PCR analysis showed that hydrogenase gene (hycl) expression increased exponentially after the addition of MnFe 2O4 NPs, and increasing the fermentation temperature improved the hydrogenase activity. We found that MnFe 2O4 NPs promoted to bio-H2 production in both mesophilic and thermophilic fermentation, and it contributed more significantly to thermophilic fermentation than mesophilic fermentation.

Walnut bacterial blight caused by Xanthomonas arboricola pv. juglandis has serious repercussions for walnut production around the world. Between 2015 and 2017, disease samples were collected from six counties (Danjiangkou, Baokang, Suizhou, Shennongjia, Zigui, and Xingshan) in Hubei Province, China. Fifty-nine X. arboricola pv. juglandis isolates were identified by morphology and specific PCR primers from 206 isolates. The genetic diversity of 60 X. arboricola pv. juglandis isolates (59 from Hubei plus 1 from Beijing) was evaluated by multilocus sequence analysis, and their resistance to copper ion (Cu2+) treatment was determined. A neighbor-joining phylogenetic dendrogram was constructed based on four sequences of housekeeping genes (atpD-dnaK-glnA-gyrB). Two groups of isolates whose clustering was consistent with that of glnA were identified. The minimal inhibitory concentration of Cu2+ on representative X. arboricola pv. juglandis strain DW3F3 (the first genome sequenced X. arboricola pv. juglandis from China) was 115 μg/ml. Setting the copper-resistant threshold value to 125 μg/ml, 47 and 13 isolates were considered sensitive and resistant to Cu2+, respectively. Furthermore, five isolates showed Cu2+ resistance at 270 μg/ml. Compared with the copper resistance gene B (copB) from sensitive isolates, the copB gene in resistant isolates had a 15-bp insertion and eight scattered single-nucleotide polymorphisms. Interestingly, the clustering based on multilocus sequence analysis was distinct between X. arboricola pv. juglandis Cu2+-resistant and -sensitive isolates.

Interpreting the formation of genomic variation landscape, especially genomic regions with elevated differentiation (i.e. islands), is fundamental to a better understanding of the genomic consequences of adaptation and speciation. Edaphic islands provide excellent systems for understanding the interplay of gene flow and selection in driving population divergence and speciation. However, discerning the relative contribution of these factors that modify patterns of genomic variation remains difficult. We analysed 132 genomes from five recently divergent species in Primulina genus, with four species distributed in Karst limestone habitats and the fifth one growing in Danxia habitats. We demonstrated that both gene flow and linked selection have contributed to genome-wide variation landscape, where genomic regions with elevated differentiation (i.e., islands) were largely derived by divergent sorting of ancient polymorphism. Specifically, we identified several lineage-specific genomic islands that might have facilitated adaptation of P. suichuanensis to Danxia habitats. Our study is amongst the first cases disentangling evolutionary processes that shape genomic variation of plant specialists, and demonstrates the important role of ancient polymorphism in the formation of genomic islands that potentially mediate adaptation and speciation of endemic plants in special soil habitats.

Small RNAs (sRNAs) constitute a large portion of functional elements in eukaryotic genomes. Long inverted repeats (LIRs) can be transcribed into long hairpin RNAs (hpRNAs), which can further be processed into small interfering RNAs (siRNAs) with vital biological roles. In this study, we systematically identified a total of 6 619 473 LIRs in 424 eukaryotic genomes and developed LIRBase (https://venyao.xyz/lirbase/), a specialized database of LIRs across different eukaryotic genomes aiming to facilitate the annotation and identification of LIRs encoding long hpRNAs and siRNAs. LIRBase houses a comprehensive collection of LIRs identified in a wide range of eukaryotic genomes. In addition, LIRBase not only allows users to browse and search the identified LIRs in any eukaryotic genome(s) of interest available in GenBank, but also provides friendly web functionalities to facilitate users to identify LIRs in user-uploaded sequences, align sRNA sequencing data to LIRs, perform differential expression analysis of LIRs, predict mRNA targets for LIR-derived siRNAs, and visualize the secondary structure of candidate long hpRNAs encoded by LIRs. As demonstrated by two case studies, collectively, LIRBase bears the great utility for systematic investigation and characterization of LIRs and functional exploration of potential roles of LIRs and their derived siRNAs in diverse species.

Giardia duodenalis is a common intestinal parasite in various hosts, with the disease giardiasis being a zoonosis. The use of molecular typing tools has improved our understanding of the distribution and zoonotic potential of G. duodenalis genotypes in different animals. The present review summarizes recent data on the distribution of G. duodenalis genotypes in humans and animals in different areas. The dominance of G. duodenalis assemblages A and B in humans and common occurrence of host-adapted assemblages in most domesticated animals suggests that zoonotic giardiasis is probably less common than believed and could be attributed mainly to contact with or contamination from just a few species of animals such as nonhuman primates, equines, rabbits, guinea pigs, chinchillas, and beavers. Future studies should be directed to advanced genetic characterization of isolates from well-designed epidemiological investigations, especially comparative analyses of isolates from humans and animals living in the same household or community. This will likely lead to better understanding of zoonotic transmission of G. duodenalis in different environmental and socioeconomic settings.

Viral infectious diseases are a devastating and continuing threat to human and animal health. Receptor binding is the key step for viral entry into host cells. Therefore, recognizing viral receptors is fundamental for understanding the potential tissue tropism or host range of these pathogens. The rapid advancement of single-cell RNA sequencing (scRNA-seq) technology has paved the way for studying the expression of viral receptors in different tissues of animal species at single-cell resolution, resulting in huge scRNA-seq datasets. However, effectively integrating or sharing these datasets among the research community is challenging, especially for laboratory scientists. In this study, we manually curated up-to-date datasets generated in animal scRNA-seq studies, analyzed them using a unified processing pipeline, and comprehensively annotated 107 viral receptors in 142 viruses and obtained accurate expression signatures in 2 100 962 cells from 47 animal species. Thus, the VThunter database provides a user-friendly interface for the research community to explore the expression signatures of viral receptors. VThunter offers an informative and convenient resource for scientists to better understand the interactions between viral receptors and animal viruses and to assess viral pathogenesis and transmission in species. Database URL: https://db.cngb.org/VThunter/.

Psoriasis is a chronic inflammatory skin disease characterized by massive keratinocyte proliferation and immune cell infiltration into the epidermis. However, the specific mechanisms underlying the development of psoriasis remain unclear. Untargeted metabolomics and transcriptomics have been used separately to profile biomarkers and risk genes in the serum of psoriasis patients. However, the integration of metabolomics and transcriptomics to identify dysregulated metabolites and genes in the psoriatic skin is lacking. In this study, we performed an untargeted metabolomics analysis of imiquimod (IMQ)-induced psoriasis-like mice and healthy controls, and found that levels of a total of 4,188 metabolites differed in IMQ-induced psoriasis-like mice compared with those in control mice. Metabolomic data analysis using MetaboAnalyst showed that the metabolic pathways of primary metabolites, such as folate biosynthesis and galactose metabolism, were significantly altered in the skin of mice after treatment with IMQ. Furthermore, IMQ treatment also significantly altered metabolic pathways of secondary metabolites, including histidine metabolism, in mouse skin tissues. The metabolomic results were verified by transcriptomics analysis. RNA-seq results showed that histamine decarboxylase (HDC) mRNA levels were significantly upregulated after IMQ treatment. Targeted inhibition of histamine biosynthesis process using HDC-specific inhibitor, pinocembrin (PINO), significantly alleviated epidermal thickness, downregulated the expression of interleukin (IL)-17A and IL-23, and inhibited the infiltration of immune cells during IMQ-induced psoriasis-like skin inflammation. In conclusion, our study offers a validated and comprehensive understanding of metabolism during the development of psoriasis and demonstrated that PINO could protect against IMQ-induced psoriasis-like skin inflammation.

Schizophrenia is a debilitating mental disorder and often has a prodromal period, referred to as clinical high risk (CHR) for psychosis, prior to the first episode. The etiology and pathogenesis of schizophrenia remain unclear. Despite the human gut microbiome being associated with schizophrenia, the role of the oral microbiome, which is a vital player in the mouth–body connection, is not well understood. To address this, we performed 16S rRNA gene sequencing to investigate the salivary microbiome in 85 patients with drug-naïve first-episode schizophrenia (FES), 43 individuals at CHR, and 80 healthy controls (HCs). The salivary microbiome of FES patients was characterized by higher α-diversity and lower β-diversity heterogeneity than those of CHR subjects and HCs. Proteobacteria, the predominant phylum, was depleted, while Firmicutes and the Firmicutes/Proteobacteria ratio was enriched, in a stepwise manner from HC to CHR to FES. H2S-producing bacteria exhibited disease-stage-specific enrichment and could be potential diagnostic biomarkers for FES and CHR. Certain salivary microbiota exhibited disease-specific correlation patterns with symptomatic severities, peripheral pro-inflammatory cytokines, thioredoxin, and S100B in FES. Furthermore, the metabolic functions from inferred metagenomes of the salivary microbiome were disrupted in FES, especially amino acid metabolism, carbohydrate metabolism, and xenobiotic degradation. This study has established a link between salivary microbiome alterations and disease initiation and provided the hypothesis of how the oral microbiota could influence schizophrenia.

Hepatocellular carcinoma (HCC) is the most common malignant liver disease in the world. Existing screening and early diagnosis methods are not highly sensitive for HCC, and patients are likely to develop the disease to the middle and advanced stages before being diagnosed. Therefore, finding new and efficient diagnosis and treatment methods has become an urgent problem. We aimed at finding and verifying new liver cancer markers by combining informatics analysis with experimental exploration to provide new ideas and methods for the diagnosis and treatment of clinical liver cancer. We used two different bioinformatic pipelines to analyze sequencing data of clinical liver cancer samples and identify differentially expressed genes and key variants after combining them with The Cancer Genome Atlas sequencing data. Then, we explored the functions and mechanisms of the key variants to identify potential liver cancer markers. Through bioinformatic analysis of sequencing data, 139 differentially expressed genes were found, including 53 upregulated genes and 86 downregulated genes. Through enrichment and alternative splicing event analysis of sequencing data, we found nine key variants with exon skipping events. Metallothionein 1E (MT1E)-203 was found to be a key variant that influenced cell proliferation through the p53 cell cycle pathway through cell viability and proliferation assays, and MT1E-203 lost the ability to bind two zinc ions due to exon skipping according to the structure prediction of MT1E-203. MT1E-203 is a potential biomarker for HCC and may play an important role in the diagnosis and treatment of HCC.

Diffuse large B-cell lymphoma (DLBCL) presents a great clinical challenge and has a poor prognosis, with immune-related genes playing a crucial role. We aimed to develop an immune-related prognostic signature for improving prognosis prediction in DLBCL. Samples from the GSE31312 dataset were randomly allocated to discovery and internal validation cohorts. Univariate Cox, random forest, LASSO regression and multivariate Cox analyses were utilized to develop a prognostic signature, which was verified in the internal validation cohort, entire validation cohort and external validation cohort (GSE10846). The tumor microenvironment was investigated using the CIBERSORT and ESTIMATE tools. Gene set enrichment analysis (GSEA) was further applied to analyze the entire GSE31312 cohort. We identified four immune-related genes (CD48, IL1RL, PSDM3, RXFP3) significantly associated with overall survival. Based on discovery and validation cohort analyses, this four-gene signature could classify patients into high- and low-risk groups, with significantly different prognoses. Activated memory CD4 T cells and activated dendritic cells were significantly decreased in the high-risk group, and these patients had lower immune scores. GSEA revealed enrichment of signaling pathways, such as T cell receptor, antigen receptor-mediated, antigen processing and presentation of peptide antigen via MHC class I, in the low-risk group. In conclusion, a robust signature based on four immune-related genes was successfully constructed for predicting prognosis in DLBCL patients.

Trichosporon are naturally found in external environments and are a part of the normal flora of the human skin, respiratory tract, and gastrointestinal tract. Disseminated Trichosporon infection occurs sporadically in patients with immunodeficiency, and is mainly manifested as blood, urine, catheter, and thorax/peritoneum infections, rarely as lymphatic, liver and spleen infections. Elevated blood eosinophil granulocyte from Trichosporon infection have rarely been reported. Here, we report a rare Case of eosinophilia associated with lymphatic and liver and spleen infections due to Trichosporon asahii in an immunocompetent patient. No reports of eosinophilia from Trichosporon infections other than lung, to our knowledge, have been published.

Although alterations in chromatin structure are known to exist in tumors, how these alterations relate to molecular phenotypes in cancer remains to be demonstrated. Multi-omics profiling of human tumors can provide insight into how alterations in chromatin structure are propagated through the pathway of gene expression to result in malignant protein expression. We applied multi-omics profiling of chromatin accessibility, RNA abundance, and protein abundance to 36 human thyroid cancer primary tumors, metastases, and patient-match normal tissue. Through quantification of chromatin accessibility associated with active transcription units and global protein expression, we identify a local chromatin structure that is highly correlated with coordinated RNA and protein expression. In particular, we identify enhancers located within gene-bodies as predictive of correlated RNA and protein expression, that is independent of overall transcriptional activity. To demonstrate the generalizability of these findings we also identify similar results in an independent cohort of human breast cancers. Taken together, these analyses suggest that local enhancers, rather than distal enhancers, are likely most predictive of cancer gene expression phenotypes. This allows for identification of potential targets for cancer therapeutic approaches and reinforces the utility of multi-omics profiling as a methodology to understand human disease., Studies show the cancer transcriptome correlates poorly with the cancer proteome, questioning the role of chromatin regulation. Here the authors demonstrate proximal-gene-body chromatin elements and transcription predict abundances of differentially expressed proteins in thyroid and breast cancers.

BGB-3111, a novel Bruton's tyrosine kinase (BTK) inhibitor, shows promising anti-cancer effects in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), and Waldenstrom macroglobulinemia (WM). This study aimed to investigate the anti-cancer effects of BGB-3111 combined with bortezomib (BTZ) against the BTK-expressing MCL. We found that BTK, which was overexpressed in 59.4% of patients with MCL, was mainly characterized by high Ki67 and elevated MIPI scores. BGB-3111 strongly inhibited cell proliferation, induced cell cycle arrest in the G1/G0-phase, and promoted cell apoptosis in the MCL cells expressing BTK. BGB-3111 provides better safety than another BTK inhibitor, ibrutinib as ibrutinib inhibits the inducible T-cell kinase (ITK) as an off-target effect but BGB-3111 does not inhibit ITK. Low doses of BTZ enhanced the anti-cancer effect induced by the low dose of BGB-3111 by downregulating the expression levels of PARP and Bcl-2 and increasing the expression levels of cleaved PARP and cleaved caspase-9. In addition, low doses of BGB-3111, but not of BTZ, inhibited BTK phosphorylation. However, low-doses of BTZ strengthened the anti-cancer effect induced by the low-doses of BGB-3111 via synergistically suppressing the IκBα and P65 phosphorylation. Taken together, our findings validate that BGB-3111 is a novel and effective BTK inhibitor for MCL-expressing BTK. Hence, it can be harnessed as a potential therapeutic strategy through a combinatorial treatment comprising low-dose BGB-3111 and low-dose BTZ to gain strong anti-cancer effects and better safety for MCL patients.

In China, agroforestry is a traditional practice that diversifies agricultural production and enhances natural resource utilization; however, it create competition for light between trees and understory crops due to heterogeneous spatio-temporal light patterns, and can lead to systemic reductions in grain yield as shade increases. The present study simulated reductions in light intensity caused by walnut trees (Juglans regia L.) before budburst, between budburst to tree foliage expansion, and after foliage expansion, to examine the effects on wheat (Triticum aestivum L.) yield and quality in an agroforestry system. We designed artificial shading systems using black polyethylene screen of varying density (21 %, 44 and 74%reductions in light intensity) at the jointing (approximately 70 d of shading), booting (approximately 55 d of shading), and anthesis (approximately 40 d of shading) stages, with full solar radiation (S0) as a control. Reduced light intensity significantly decreased the number of fertile florets per spike, resulting in a marked decline in grains per spike. Decreased light intensity also significantly decreased photosynthetic rates, grain yield and associated components (spike number, grains per spike, and thousand-grain weight), Furthermore, when applied at the anthesis stage, shading had the strongest negative impact on wheat productivity via decreases in thousand-grain weight. Decreased light intensity substantially enhanced grain and stalk nitrogen concentrations, as well as protein and wet gluten contents. However, the increase in grain quality did not compensate for the decreased final grain yield. Our evaluation of the effect of heterogeneous spatio-temporal light patterns on wheat yield and quality via an artificial shade system may help plantation managers to optimize agroforestry practices in Southern Xinjiang, Northwest China.

Hantaan virus infection may cause severe lethal hemorrhagic fever with renal syndrome (HFRS) in humans. The chemokine fractalkine (CX3CL1) acts as a proinflammatory cytokine, and it is elevated in several infectious diseases. However, little is known about the contributions of CX3CL1 to HFRS pathogenesis. Present study detected plasma CX3CL1 levels and expression of the receptor CX3CR1 in HFRS patients and discussed the possible effects of CX3CL1 on pathogenesis of HFRS. Plasma CX3CL1 in acute phase and Critical/Severe groups of HFRS patients were significantly increased compared to that in normal controls (

Chromosome 22q11.2 deletion syndrome is a common inborn error of immunity. The early consequences of thymic hypoplasia are low T cell numbers. Later in life, atopy, autoimmunity, inflammation, and evolving hypogammaglobulinemia can occur and the causes of these features are not understood. This study utilized an unbiased discovery approach to define alterations in histone modifications. Our goal was to identify durable chromatin changes that could influence cell behavior. CD4 T cells and CD19 B cells underwent ChIP-seq analysis using antibodies to H3K4me3, H3K27ac, and H4ac. RNA effects were defined in CD4 T cells by RNA-seq. Serum cytokines were examined by Luminex. Histone marks of transcriptional activation at CD4 T cell promoters and enhancers were globally increased. The promoter activation signature had elements related to T cell activation and inflammation, concordant with effects seen in the transcriptome. B cells, in contrast, had a minimally altered epigenetic landscape in 22q11.2. Both cell types had an “edge” effect with markedly altered chromatin adjacent to the deletion. People with 22q11.2 deletion have altered CD4 T cell chromatin and a transcriptome concordant with the changes in the epigenome. These effects support a disease model where qualitative changes to T cells occur in addition to quantitative defects that have been well characterized. This study offers unique insight into qualitative differences in the T cells in 22q11.2 deletion, an aspect that has received limited attention.

Acute lung injury (ALI) is mainly caused by severe infection, shock, trauma, and burn, which causes the extensive release of inflammatory factors and other mediators. As a major bioactive constituent of traditional Chinese herb licorice, glycyrrhizic acid (GA) plays an important effect on inflammatory regulation. Nevertheless, the exact mechanism of this effect remains unclear. The present study aims to explore the potential protective effect of GA on LPS-induced ALI. Our results showed that GA significantly attenuated LPS-induced ALI and decreased the production of inflammatory factors, including IL-1β, MCP-1, COX2, HMGB1, and adhesion molecules, such as E-selectin, VCAM-1, and modulated expression of angiotensin-converting enzyme 2 (ACE2). Moreover, treatment of ACE2 inhibitor (MLN-4760) reversed the effects of GA on the secretion of pro-inflammatory factors in ALI. Additionally, GA exerts its protective effect by regulating the ACE2 and caveolin-1/NF-κB signaling pathway. In conclusion, this study showed that GA alleviated LPS-induced ALI by upregulating ACE2 and inhibiting the caveolin-1/NF-κB signaling pathway.