Achieving long-lived white circularly polarized luminescence from carbonized polymer dots via phosphorescence resonance energy transfer.

Achieving white-light emission, especially long-lived white circularly polarized luminescence, is challenging. Herein, chiral phosphorescent carbonized polymer dots (CPDs) have been prepared by using chiral polymer sodium alginate and chiral small molecule L-lysine as precursors. Benefiting from the efficient triplet-to-singlet phosphorescence resonance energy transfer (PRET), CPD-based long-lived warm white CPL has been achieved for the first time. This study provides a universal strategy for the convenient and efficient preparation of CPD-based long-lived white CPL materials.

Genome-wide analysis of the peanut CaM/CML gene family reveals that the AhCML69 gene is associated with resistance to Ralstonia solanacearum.

BACKGROUND: Calmodulins (CaMs)/CaM-like proteins (CMLs) are crucial Ca2+-binding sensors that can decode and transduce Ca2+ signals during plant development and in response to various stimuli. The CaM/CML gene family has been characterized in many plant species, but this family has not yet been characterized and analyzed in peanut, especially for its functions in response to Ralstonia solanacearum. In this study, we performed a genome-wide analysis to analyze the CaM/CML genes and their functions in resistance to R. solanacearum. RESULTS: Here, 67, 72, and 214 CaM/CML genes were identified from Arachis duranensis, Arachis ipaensis, and Arachis hypogaea, respectively. The genes were divided into nine subgroups (Groups I-IX) with relatively conserved exon‒intron structures and motif compositions. Gene duplication, which included whole-genome duplication, tandem repeats, scattered repeats, and unconnected repeats, produced approximately 81 pairs of homologous genes in the AhCaM/CML gene family. Allopolyploidization was the main reason for the greater number of AhCaM/CML members. The nonsynonymous (Ka) versus synonymous (Ks) substitution rates (less than 1.0) suggested that all homologous pairs underwent intensive purifying selection pressure during evolution. AhCML69 was constitutively expressed in different tissues of peanut plants and was involved in the response to R. solanacearum infection. The AhCML69 protein was localized in the cytoplasm and nucleus. Transient overexpression of AhCML69 in tobacco leaves increased resistance to R. solanacearum infection and induced the expression of defense-related genes, suggesting that AhCML69 is a positive regulator of disease resistance. CONCLUSIONS: This study provides the first comprehensive analysis of the AhCaM/CML gene family and potential genetic resources for the molecular design and breeding of peanut bacterial wilt resistance.

Chiral Aggregation-Induced Emission Carbon Dot-Based Multicolor and Near-Infrared Circularly Polarized Delayed Fluorescence via a Light-Harvesting System.

Circularly polarized luminescence (CPL) materials are the research frontier of chiral luminescence. As a kind of luminescent carbon material, carbon dots (CDs) are expected to become excellent candidates for the construction of CPL materials. However, the construction of CD-based circularly polarized afterglow emission, especially multicolor and near-infrared emission, remains a great challenge due to aggregation-caused quenching and the instability of triplet excitons. In this work, we synthesized chiral CDs with aggregation-induced emission using dithiosalicylic acid and l/d-arginine as precursors through a one-step solvothermal method. Notably, the CDs exhibit green delayed fluorescence (DF) in poly(vinyl alcohol) films. Furthermore, multicolor and near-infrared circularly polarized delayed fluorescence is successfully realized via engineering a chiral light-harvesting system in which the CDs with green DF emission act as energy donors and fluorescent dyes with emission colors ranging from yellow to the near infrared serve as energy acceptors.

STING activation in TET2-mutated hematopoietic stem/progenitor cells contributes to the increased self-renewal and neoplastic transformation.

Somatic loss-of-function mutations of the dioxygenase Ten-eleven translocation-2 (TET2) occur frequently in individuals with clonal hematopoiesis (CH) and acute myeloid leukemia (AML). These common hematopoietic disorders can be recapitulated in mouse models. However, the underlying mechanisms by which the deficiency in TET2 promotes these disorders remain unclear. Here we show that the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway is activated to mediate the effect of TET2 deficiency in dysregulated hematopoiesis in mouse models. DNA damage arising in Tet2-deficient hematopoietic stem/progenitor cells (HSPCs) leads to activation of the cGAS-STING pathway which in turn promotes the enhanced self-renewal and development of CH. Notably, both pharmacological inhibition and genetic deletion of STING suppresses Tet2 mutation-induced aberrant hematopoiesis. In patient-derived xenograft (PDX) models, STING inhibition specifically attenuates the proliferation of leukemia cells from TET2-mutated individuals. These observations suggest that the development of CH associated with TET2 mutations is powered through chronic inflammation dependent on the activated cGAS-STING pathway and that STING may represent a potential target for intervention of relevant hematopoietic diseases.

Treating solid tumors with TCR-based chimeric antigen receptor targeting extra domain B-containing fibronectin.

BACKGROUND: The suppression of chimeric antigen receptor (CAR) T cells by the tumor microenvironment (TME) is a crucial obstacle in the T-cell-based treatment of solid tumors. Extra domain B (EDB)-fibronectin is an oncofetal antigen expressed on the endothelium layer of the neovasculature and cancer cells. Though recognized as a T cell therapy target, engineered CAR T cells thus far have failed to demonstrate satisfactory in vivo efficacy. In this study, we report that targeting EDB-fibronectin by redirected TCR-CAR T cells (rTCR-CAR) bypasses the suppressive TME for solid tumor treatment and sufficiently suppressed tumor growth.We generated EDB-targeting CAR by fusing single-chain variable fragment to CD3ε, resulting in rTCR-CAR. Human primary T cells and Jurkat cells were used to study the EDB-targeting T cells. Differences to the traditional second-generation CAR T cell in signaling, immune synapse formation, and T cell exhaustion were characterized. Cytotoxicity of the rTCR-CAR T cells was tested in vitro, and therapeutic efficacies were demonstrated using xenograft models. METHODS: RESULTS: In the xenograft models, the rTCR-CAR T cells demonstrated in vivo efficacies superior to that based on traditional CAR design. A significant reduction in tumor vessel density was observed alongside tumor growth inhibition, extending even to tumor models established with EDB-negative cancer cells. The rTCR-CAR bound to immobilized EDB, and the binding led to immune synapse structures superior to that formed by second-generation CARs. By a mechanism similar to that for the conventional TCR complex, EDB-fibronectin activated the rTCR-CAR, resulting in rTCR-CAR T cells with low basal activation levels and increased in vivo expansion. CONCLUSION: Our study has demonstrated the potential of rTCR-CAR T cells targeting the EDB-fibronectin as an anticancer therapeutic. Engineered to possess antiangiogenic and cytotoxic activities, the rTCR-CAR T cells showed therapeutic efficacies not impacted by the suppressive TMEs. These combined characteristics of a single therapeutic agent point to its potential to achieve sustained control of solid tumors.

Characteristics of Extended-Spectrum ß-Lactamase-Producing Escherichia coli Derived from Food and Humans in Northern Xinjiang, China.

This study aimed to investigate the drug resistance, molecular characteristics, and genetic relationship of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli isolated from food and human stool samples in northern Xinjiang. From 2015 to 2016, a total of 431 samples (meats and vegetables) were collected from retail markets and supermarkets located in the regions of Urumqi, Shihezi, and Kuitun in Xinjiang, China, and 20 human stool samples from the Shihezi Hospital. The PCR method was used to detect E. coli, and the presence of ESBL-producing E. coli was confirmed using the K-B disk diffusion confirmatory method. The susceptibility to ESBL-producing E. coli was tested by the microdilution broth method, and the minimum inhibitory concentration was determined. PCR was used to detect the resistance and virulence genes of ESBL-producing E. coli, and phylogenetics, plasmid replicon typing, screening of three integrons, and multilocus sequence typing (MLST) were performed. The results showed that 127 E. coli strains (15 human stool and 112 food samples) were isolated. Out of the 127 E. coli strains, 38 strains (6 human stool and 32 food 34 samples) of ESBL-producing E. coli were identified through screening. These 38 strains showed resistance to cefotaxime (94.74%) and cefepime (94.74%), and were sensitive to meropenem (0.00%). The most detected resistance genes were blaTEM (47.37%), and the most detected virulence genes were fimH (97.73%), ompA (97.73%), hlyE (97.73%), and crl (97.37%). The isolates belonged to phylogroups B1 (42.11%), C (23.68%), and A (21.05%). Among the plasmid replicon subtypes, IncFIB was the main type (42.11%). The integrons detected were of the first type (47.37%) and the third type (26.32%). The 38 E. coli strains had 19 different sequence-type (ST) strains. These 38 strains of ESBL-producing E. coli were analyzed using MLST and STs are varied.

Light-Driven Synthetic Biology: Progress in Research and Industrialization of Cyanobacterial Cell Factory.

Light-driven synthetic biology refers to an autotrophic microorganisms-based research platform that remodels microbial metabolism through synthetic biology and directly converts light energy into bio-based chemicals. This technology can help achieve the goal of carbon neutrality while promoting green production. Cyanobacteria are photosynthetic microorganisms that use light and CO2 for growth and production. They thus possess unique advantages as "autotrophic cell factories". Various fuels and chemicals have been synthesized by cyanobacteria, indicating their important roles in research and industrial application. This review summarized the progresses and remaining challenges in light-driven cyanobacterial cell factory. The choice of chassis cells, strategies used in metabolic engineering, and the methods for high-value CO2 utilization will be discussed.

The prevalence and characteristics of extended-spectrum ß-lactamase Escherichia coli in raw milk and dairy farms in Northern Xinjiang, China.

In this study, extended-spectrum ß-lactamase (ESBL) Escherichia coli were isolated from five dairy farms in three areas of northern Xinjiang, China. Molecular biological techniques were used to systematically analyze drug resistance phenotypes and genotypes, virulence genes, phylogenetics, biofilm formation (BF), and pulsed field gel electrophoresis (PFGE) typing of isolated ESBL E. coli strains. A total of 766 samples were collected from five dairy farms in Shihezi, Urumqi and Yili, from which 149 (19.5 %, 95 % CI: 16.65 %-22.25 %) ESBL E. coli strains were isolated. Their distribution and contamination levels varied from region to region, with 16.2 % (68/419) in Urumqi, 22.4 % (60/268) in Shihezi, and 26.6 % (21/79) in Yili. The majority of isolates (97.3 %, 145/149) harbored the ß-lactamase blaCTX-M gene; while blaCTX-M-1 was the dominant phylogenetic group. The analysis of 21 resistance genes and the susceptibility to 13 different antibiotics showed that 91.3 % (136/149) of strains were resistant to three or more antibiotics. Thirty-six strains (24.2 %) belonged to extraintestinal pathogenic E. coli (ExPEC), and phylogenetic typing results were mainly grouped A (50.3 %) and B1 (37.6 %). Also, the biofilm assay revealed that 112 strains (75.2 %) could form biofilms. PFGE results showed that the 49 isolates revealed 21 major pulsotypes (P1-P21) and 28 subtypes with 80 % similarity, indicating the overall genetic diversity in the distribution area and sources of the samples.

Comparative transcriptome analysis revealed molecular mechanisms of peanut leaves responding to Ralstonia solanacearum and its type III secretion system mutant.

Bacterial wilt caused by Ralstonia solanacearum is a serious soil-borne disease that limits peanut production and quality, but the molecular mechanisms of the peanut response to R. solanacearum remain unclear. In this study, we reported the first work analyzing the transcriptomic changes of the resistant and susceptible peanut leaves infected with R. solanacearum HA4-1 and its type III secretion system mutant strains by the cutting leaf method at different timepoints (0, 24, 36, and 72 h post inoculation). A total of 125,978 differentially expressed genes (DEGs) were identified and subsequently classified into six groups to analyze, including resistance-response genes, susceptibility-response genes, PAMPs induced resistance-response genes, PAMPs induced susceptibility-response genes, T3Es induced resistance-response genes, and T3Es induced susceptibility-response genes. KEGG enrichment analyses of these DEGs showed that plant-pathogen interaction, plant hormone signal transduction, and MAPK signaling pathway were the outstanding pathways. Further analysis revealed that CMLs/CDPKs-WRKY module, MEKK1-MKK2-MPK3 cascade, and auxin signaling played important roles in the peanut response to R. solanacearum. Upon R. solanacearum infection (RSI), three early molecular events were possibly induced in peanuts, including Ca2+ activating CMLs/CDPKs-WRKY module to regulate the expression of resistance/susceptibility-related genes, auxin signaling was induced by AUX/IAA-ARF module to activate auxin-responsive genes that contribute to susceptibility, and MEKK1-MKK2-MPK3-WRKYs was activated by phosphorylation to induce the expression of resistance/susceptibility-related genes. Our research provides new ideas and abundant data resources to elucidate the molecular mechanism of the peanut response to R. solanacearum and to further improve the bacterial wilt resistance of peanuts.

Complete Genome Sequence Analysis of Ralstonia solanacearum Strain PeaFJ1 Provides Insights Into Its Strong Virulence in Peanut Plants.

The bacterial wilt of peanut (Arachis hypogaea L.) caused by Ralstonia solanacearum is a devastating soil-borne disease that seriously restricted the world peanut production. However, the molecular mechanism of R. solanacearum-peanut interaction remains largely unknown. We found that R. solanacearum HA4-1 and PeaFJ1 isolated from peanut plants showed different pathogenicity by inoculating more than 110 cultivated peanuts. Phylogenetic tree analysis demonstrated that HA4-1 and PeaFJ1 both belonged to phylotype I and sequevar 14M, which indicates a high degree of genomic homology between them. Genomic sequencing and comparative genomic analysis of PeaFJ1 revealed 153 strain-specific genes compared with HA4-1. The PeaFJ1 strain-specific genes consisted of diverse virulence-related genes including LysR-type transcriptional regulators, two-component system-related genes, and genes contributing to motility and adhesion. In addition, the repertoire of the type III effectors of PeaFJ1 was bioinformatically compared with that of HA4-1 to find the candidate effectors responsible for their different virulences. There are 79 effectors in the PeaFJ1 genome, only 4 of which are different effectors compared with HA4-1, including RipS4, RipBB, RipBS, and RS_T3E_Hyp6. Based on the virulence profiles of the two strains against peanuts, we speculated that RipS4 and RipBB are candidate virulence effectors in PeaFJ1 while RipBS and RS_T3E_Hyp6 are avirulence effectors in HA4-1. In general, our research greatly reduced the scope of virulence-related genes and made it easier to find out the candidates that caused the difference in pathogenicity between the two strains. These results will help to reveal the molecular mechanism of peanut-R. solanacearum interaction and develop targeted control strategies in the future.