Therapeutic efficacy of a novel self-assembled immunostimulatory siRNA combining apoptosis promotion with RIG-I activation in gliomas.

BACKGROUND: Current cancer therapies often fall short in addressing the complexities of malignancies, underscoring the urgent need for innovative treatment strategies. RNA interference technology, which specifically suppresses gene expression, offers a promising new approach in the fight against tumors. Recent studies have identified a novel immunostimulatory small-interfering RNA (siRNA) with a unique sequence (sense strand, 5'-C; antisense strand, 3'-GGG) capable of activating the RIG-I/IRF3 signaling pathway. This activation induces the release of type I and III interferons, leading to an effective antiviral immune response. However, this class of immunostimulatory siRNA has not yet been explored in cancer therapy. METHODS: IsiBCL-2, an innovative immunostimulatory siRNA designed to suppress the levels of B-cell lymphoma 2 (BCL-2), contains a distinctive motif (sense strand, 5'-C; antisense strand, 3'-GGG). Glioblastoma cells were subjected to 100 nM isiBCL-2 treatment in vitro for 48 h. Morphological changes, cell viability (CCK-8 assay), proliferation (colony formation assay), migration/invasion (scratch test and Transwell assay), apoptosis rate, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were evaluated. Western blotting and immunofluorescence analyses were performed to assess RIG-I and MHC-I molecule levels, and ELISA was utilized to measure the levels of cytokines (IFN-ß and CXCL10). In vivo heterogeneous tumor models were established, and the anti-tumor effect of isiBCL-2 was confirmed through intratumoral injection. RESULTS: IsiBCL-2 exhibited significant inhibitory effects on glioblastoma cell growth and induced apoptosis. BCL-2 mRNA levels were significantly decreased by 67.52%. IsiBCL-2 treatment resulted in an apoptotic rate of approximately 51.96%, accompanied by a 71.76% reduction in MMP and a 41.87% increase in ROS accumulation. Western blotting and immunofluorescence analyses demonstrated increased levels of RIG-I, MAVS, and MHC-I following isiBCL-2 treatment. ELISA tests indicated a significant increase in IFN-ß and CXCL10 levels. In vivo studies using nude mice confirmed that isiBCL-2 effectively impeded the growth and progression of glioblastoma tumors. CONCLUSIONS: This study introduces an innovative method to induce innate signaling by incorporating an immunostimulatory sequence (sense strand, 5'-C; antisense strand, 3'-GGG) into siRNA, resulting in the formation of RNA dimers through Hoogsteen base-pairing. This activation triggers the RIG-I signaling pathway in tumor cells, causing further damage and inducing a potent immune response. This inventive design and application of immunostimulatory siRNA offer a novel perspective on tumor immunotherapy, holding significant implications for the field.

Atom Pairing Enhances Sulfur Resistance in Low-Temperature SCR via Upshifting the Lowest Unoccupied States of Cerium.

Environmentally benign cerium-based catalysts are promising alternatives to toxic vanadium-based catalysts for controlling NOx emissions via selective catalytic reduction (SCR), but conventional cerium-based catalysts unavoidably suffer from SO2 poisoning in low-temperature SCR. We develop a strongly sulfur-resistant Ce1+1/TiO2 catalyst by spatially confining Ce atom pairs to different anchoring sites of anatase TiO2(001) surfaces. Experimental results combined with theoretical calculations demonstrate that strong electronic interactions between the paired Ce atoms upshift the lowest unoccupied states to an energy level higher than the highest occupied molecular orbital (HOMO) of SO2 so as to be catalytically inert in SO2 oxidation but slightly lower than HOMO of NH3 so that Ce1+1/TiO2 has desired ability toward NH3 activation required for SCR. Hence, Ce1+1/TiO2 shows higher SCR activity and excellent stability in the presence of SO2 at low temperatures with respect to supported single Ce atoms. This work provides a general strategy to develop sulfur-resistant catalysts by tuning the electronic states of active sites for low-temperature SCR, which has implications for practical applications with energy-saving requirements.

Metabolomic analysis of hydroxycinnamic acid inhibition on Saccharomyces cerevisiae.

Ferulic acid (FA) and p-coumaric acid (p-CA) are hydroxycinnamic acid inhibitors that are mainly produced during the pretreatment of lignocellulose. To date, the inhibitory mechanism of hydroxycinnamic acid compounds on Saccharomyces cerevisiae has not been fully elucidated. In this study, liquid chromatography-mass spectrometry (LC-MS) and scanning electron microscopy (SEM) were used to investigate the changes in S. cerevisiae cells treated with FA and p-CA. In this experiment, the control group was denoted as group CK, the FA-treated group was denoted as group F, and the p-CA-treated group was denoted as group P. One hundred different metabolites in group F and group CK and 92 different metabolites in group P and group CK were selected and introduced to metaboanalyst, respectively. A total of 38 metabolic pathways were enriched in S. cerevisiae under FA stress, and 27 metabolic pathways were enriched in S. cerevisiae under p-CA stress as identified through Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis. The differential metabolites involved included S-adenosine methionine, L-arginine, and cysteine, which were significantly downregulated, and acetyl-CoA, L-glutamic acid, and L-threonine, which were significantly upregulated. Analysis of differential metabolic pathways showed that the differentially expressed metabolites were mainly related to amino acid metabolism, nucleotide metabolism, fatty acid degradation, and the tricarboxylic acid cycle (TCA). Under the stress of FA and p-CA, the metabolism of some amino acids was blocked, which disturbed the redox balance in the cells and destroyed the synthesis of most proteins, which was the main reason for the inhibition of yeast cell growth. This study provided a strong scientific reference to improve the durability of S. cerevisiae against hydroxycinnamic acid inhibitors. KEY POINTS: • Morphological changes of S. cerevisiae cells under inhibitors stress were observed. • Changes of the metabolites in S. cerevisiae cells were explored by metabolomics. • One of the inhibitory effects on yeast is due to changes in the metabolic network.

NO Selective Catalytic Reduction over Atom-Pair Active Sites Accelerated via In Situ NO Oxidation.

Selective catalytic reduction (SCR) of NOx with NH3 is the most efficient technology for NOx emissions control, but the activity of catalysts decreases exponentially with the decrease in reaction temperature, hindering the application of the technology in low-temperature SCR to treat industrial stack gases. Here, we present an industrially practicable technology to significantly enhance the SCR activity at low temperatures (<250 °C). By introducing an appropriate amount of O3 into the simulated stack gas, we find that O3 can stoichiometrically oxidize NO to generate NO2, which enables NO reduction to follow the fast SCR mechanism so as to accelerate SCR at low temperatures, and, in particular, an increase in SCR rate by more than four times is observed over atom-pair V1-W1 active sites supported on TiO2(001) at 200 °C. Using operando SCR tests and in situ diffuse reflectance infrared Fourier transform spectra, we reveal that the introduction of O3 allows SCR to proceed along a NH4NO3-mediated Langmuir-Hinshelwood model, in which the adsorbed nitrate species speed up the re-oxidation of the catalytic sites that is the rate-limiting step of SCR, thus leading to the enhancement of activity at low temperatures. This technology could be applicable in the real stack gas conditions because O3 exclusively oxidizes NO even in the co-presence of SO2 and H2O, which provides a general strategy to improve low-temperature SCR efficacy from another perspective beyond designing catalysts.

The genetic basis of grain protein content in rice by genome-wide association analysis.

The grain protein content (GPC) of rice is an important factor that determines its nutritional, cooking, and eating qualities. To date, although a number of genes affecting GPC have been identified in rice, most of them have been cloned using mutants, and only a few genes have been cloned in the natural population. In this study, 135 significant loci were detected in a genome-wide association study (GWAS), many of which could be repeatedly detected across different years and populations. Four minor quantitative trait loci affecting rice GPC at four significant association loci, qPC2.1, qPC7.1, qPC7.2, and qPC1.1, were further identified and validated in near-isogenic line F2 populations (NIL-F2), explaining 9.82, 43.4, 29.2, and 13.6% of the phenotypic variation, respectively. The role of the associated flo5 was evaluated with knockdown mutants, which exhibited both increased grain chalkiness rate and GPC. Three candidate genes in a significant association locus region were analyzed using haplotype and expression profiles. The findings of this study will help elucidate the genetic regulatory network of protein synthesis and accumulation in rice through cloning of GPC genes and provide new insights on dominant alleles for marker-assisted selection in the genetic improvement of rice grain quality. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01347-z.

Transcriptome Analysis Revealed the Dynamic and Rapid Transcriptional Reprogramming Involved in Cold Stress and Related Core Genes in the Rice Seedling Stage.

Cold damage is one of the most important environmental factors influencing crop growth, development, and production. In this study, we generated a pair of near-isogenic lines (NILs), Towada and ZL31, and Towada showed more cold sensitivity than ZL31 in the rice seedling stage. To explore the transcriptional regulation mechanism and the reason for phenotypic divergence of the two lines in response to cold stress, an in-depth comparative transcriptome study under cold stress was carried out. Our analysis uncovered that rapid and high-amplitude transcriptional reprogramming occurred in the early stage of cold treatment. GO enrichment and KEGG pathway analysis indicated that genes of the response to stress, environmental adaptation, signal transduction, metabolism, photosynthesis, and the MAPK signaling pathway might form the main part of the engine for transcriptional reprogramming in response to cold stress. Furthermore, we identified four core genes, OsWRKY24, OsCAT2, OsJAZ9, and OsRR6, that were potential candidates affecting the cold sensitivity of Towada and ZL31. Genome re-sequencing analysis between the two lines revealed that only OsWRKY24 contained sequence variations which may change its transcript abundance. Our study not only provides novel insights into the cold-related transcriptional reprogramming process, but also highlights the potential candidates involved in cold stress.

An Atom-Pair Design Strategy for Optimizing the Synergistic Electron Effects of Catalytic Sites in NO Selective Reduction.

Effective adsorption and speedy surface reactions are vital requirements for efficient active sites in catalysis, but it remains challenging to maximize these two functions simultaneously. We present a solution to this issue by designing a series of atom-pair catalytic sites with tunable electronic interactions. As a case study, NO selective reduction occurring on V1 -W1 /TiO2 is chosen. Experimental and theoretical results reveal that the synergistic electron effect present between the paired atoms enriches high-energy spin charge around the Fermi level, simultaneously rendering reactant (NH3 or O2 ) adsorption more effective and subsequent surface reactions speedier as compared with single V or W atom alone, and hence higher reaction rates. This strategy enables us to rationally design a high-performance V1 -Mo1 /TiO2 catalyst with optimized vanadium(IV)-molybdenum(V) electronic interactions, which has exceptional activity significantly higher than the commercial or reported catalysts.

Sulfur-Resistant Ceria-Based Low-Temperature SCR Catalysts with the Non-bulk Electronic States of Ceria.

Although ceria-based catalysts serve as an appealing alternative to traditional V2O5-based catalysts for selective catalytic reduction (SCR) of NOx with NH3, the inevitable deactivation caused by SO2 at low temperatures severely hampers the ceria-based catalysts to efficiently control NOx emissions from SO2-containing stack gases. Here, we rationally design a strong sulfur-resistant ceria-based catalyst by tuning the electronic structures of ceria highly dispersed on acidic MoO3 surfaces. By using Ce L3-edge X-ray absorption near edge structure spectra in conjunction with various surface and bulk structural characterizations, we report that the sulfur resistance of the catalysts is closely associated with the electronic states of ceria, particularly expressed by the Ce3+/Ce4+ ratio related to the size of the ceria particles. As the Ce3+/Ce4+ ratio increases up to or over 50%, corresponding to CeO2/MoO3(x %, x ≤ 2.1) with the particle size of approximately 4 nm or less, the non-bulk electronic states of ceria appear, where the catalysts start to show strong sulfur resistance. This work could provide a new strategy for designing sulfur-resistant ceria-based SCR catalysts for controlling NOx emissions at low temperatures.

Molecular mechanism related to the binding of fluorophores to Mango-II revealed by multiple-replica molecular dynamics simulations.

Recently, RNA aptamers activating small-molecule fluorophores have been successfully applied to tag and track RNAs in vivo. It is of significance to investigate the molecular mechanism of the fluorophore-RNA aptamer bindings at the atomic level to seek a possible pathway to enhance the fluorescence efficiency of fluorophores. In this work, multiple replica molecular dynamics (MRMD) simulations, essential dynamics (ED) analysis, and hierarchical clustering analysis were coupled to probe the effect of A22U mutation on the binding of two fluorophores, TO1-Biotin (TO1) and TO3-Biotin (TO3), to the Mango-II RNA aptamer (Mango-II). ED analysis reveals that A22U induces alterations in the binding pocket and sites of TO1 and TO3 to the Mango-II, which in turn tunes the fluorophore-RNA interface and changes the interactions of TO1 and TO3 with separate nucleotides of Mango-II. Dynamics analyses also uncover that A22U exerts the opposite impact on the molecular surface areas of the Mango-II and sugar puckers of nucleotides 22 and 23 in Mango-II complexed with TO1 and TO3. Moreover, the calculations of binding free energies suggest that A22U strengthens the binding ability of TO1 to the mutated Mango-II but weakens TO3 to the mutated Mango-II when compared with WT. These findings imply that point mutation in nucleotides possibly tune the fluorescence of fluorophores binding to RNA aptamers, providing a possible scheme to enhance the fluorescence of fluorophores.

Molecular mechanism with regard to the binding selectivity of inhibitors toward FABP5 and FABP7 explored by multiple short molecular dynamics simulations and free energy analyses.

Recently, fatty acid binding proteins 5 and 7 (FABP5 and FABP7) have been regarded as the prospective targets for clinically treating multiple diseases related to FABPs. In this work, multiple short molecular dynamics (MSMD) simulations followed by binding free energy calculations were performed to investigate the binding selectivity of three inhibitors, namely, 65X, 8KS, and 5M8 toward FABP5 and FABP7. The RMSF analysis suggests that the structural flexibility of FABP5 is stronger than that of FABP7; moreover, the calculated molecular surface area of FABP5 is also larger than that of FABP7. Meanwhile, the results from the cross-correlation analysis show that the inhibitor bindings exert different impacts on the internal dynamics of FABP5 and FABP7. Binding free energies predicted by the molecular mechanics/generalized Born surface area (MM-GBSA) method indicate that the increase in the enthalpy changes caused by the bindings of inhibitors toward FABP7 relative to FABP5 mostly drives the binding selectivity of the inhibitors toward FABP5 versus FABP7. Hierarchical clustering analysis based on the energy contributions of separate residues and calculations of residue-based free energy decompositions were carried out by using the equilibrated MSMD trajectories. The obtained results not only recognize the hot interaction spots of inhibitors with FABP5 and FABP7, but also display that several common residues, namely, (T56, T54), (L60, F58), (E75, E73), (A76, A78), (D79, D77), (R81, R79), (R107, R109), (C120, L118), and (R129, R127) belonging to (FABP5, FABP7) induce obvious binding differences in the inhibitors toward FABP5 and FABP7. Therefore, these residues play significant roles in the binding selectivities of inhibitors toward FABP5 and FABP7.

Genome-wide association analyses reveal the genetic basis of combining ability in rice.

Combining ability is a measure for selecting elite parents and predicting hybrid performance in plant breeding. However, the genetic basis of combining ability remains unclear and a global view of combining ability from diverse mating designs is lacking. We developed a North Carolina II (NCII) population of 96 Oryza sativa and four male sterile lines to identify parents of greatest value for hybrid rice production. Statistical analyses indicated that general combining ability (GCA) and specific combining ability (SCA) contributed variously to different agronomic traits. In a genome-wide association study (GWAS) of agronomic traits, GCA and SCA, we identified 34 significant associations (P < 2.39 × 10-7 ). The superior alleles of GCA loci (Ghd8, GS3 and qSSR4) accumulated in parental lines with high GCA and explained 30.03% of GCA variance in grain yield, indicating that molecular breeding of high GCA parental lines is feasible. The distinct distributions of these QTLs contributed to the differentiation of parental GCA in subpopulations. GWAS of SCA identified 12 more loci that showed dominance on corresponding agronomic traits. We conclude that the accumulation of superior GCA and SCA alleles is an important contributor to heterosis and QTLs that greatly contributed to combining ability in our study would accelerate the identification of elite inbred lines and breeding of super hybrids.

Self-Prevention of Well-Defined-Facet Fe2O3/MoO3 against Deposition of Ammonium Bisulfate in Low-Temperature NH3-SCR.

Low-temperature selective catalytic reduction of NO by NH3 (NH3-SCR) is a promising technology for controlling NO emission from various industrial boilers, but it remains challenging because unavoidable deposition of ammonium bisulfates (ABS) in the stack gases containing both SO2 and H2O inevitably results in deactivation of catalysts. Here we developed a stable low-temperature NH3-SCR catalyst by supporting Fe2O3 cubes on surfaces of MoO3 nanobelts with NH4+-intercalatable interlayers, which enables Fe2O3/MoO3 to spontaneously prevent ABS from depositing on the surfaces. Using in situ synchrotron X-ray diffraction, 1H magic angle spinning nuclear magnetic resonance, and temperature-programmed decomposition procedure, the results demonstrate that NH4+ of ABS was initially intercalated in the interlayers of MoO3, leading to a NH4+-HSO4- cation-anion separation by conquering their strong electrostatic interactions, and subsequently the separated NH4+ was consumed by taking part in low-temperature NH3-SCR. Meanwhile, the surface HSO4- separated from ABS oxidized the reduced catalyst during the NH3-SCR redox cycle, concomitant with release of SO2 gas, thereby resulting in decomposition of ABS. This work assists the design of stable low-temperature NH3-SCR catalysts with strong resistance against deposition of ABS.

Enhanced Performance of Ceria-Based NOx Reduction Catalysts by Optimal Support Effect.

CeO2-based catalysts have attracted widespread attention in environmental-protection applications, including selective catalytic reduction (SCR) of NO by NH3, and their catalytic performance is often intimately associated with the supports used. However, the issue of how to choose the supports of such catalysts still remains unresolved. Herein, we systematically study the support effect in SCR over CeO2-based catalysts by using three representative supports, Al2O3, TiO2, and hexagonal WO3 (HWO), with different acidic and redox properties. HWO, with both acidic and reducible properties, achieves an optimal support effect; that is, CeO2/HWO exhibits higher catalytic activity than CeO2 supported on acidic Al2O3 or reducible TiO2. Transmission electron microscopy and X-ray diffraction techniques demonstrate that acidic supports (HWO and Al2O3) are favorable for the dispersion of CeO2 on their surfaces. X-ray photoelectron spectroscopy coupled with theoretical calculations reveals that reducible supports (HWO and TiO2) facilitate strong electronic CeO2-support interactions. Hence, the excellent catalytic performance of CeO2/HWO is mainly ascribed to the high dispersion of CeO2 and the optimal electronic CeO2-support interactions. This work shows that abundant Brønsted acid sites and excellent redox ability of supports are two critical requirements for the design of efficient CeO2-based catalysts.

Sodium Rivals Silver as Single-Atom Active Centers for Catalyzing Abatement of Formaldehyde.

The development of efficient alkali-based catalysts for the abatement of formaldehyde (HCHO), a ubiquitous air pollutant, is economically desirable. Here we comparatively study the catalytic performance of two single-atom catalysts, Na1/HMO and Ag1/HMO (HMO = Hollandite manganese oxide), in the complete oxidation of HCHO at low temperatures, in which the products are only CO2 and H2O. These catalysts are synthesized by anchoring single sodium ions or silver atoms on HMO(001) surfaces. Synchrotron X-ray diffraction patterns with structural refinement together with transmission electron microscopy images demonstrate that single sodium ions on the HMO(001) surfaces of Na1/HMO have the same local structures as silver atoms of Ag1/HMO. Catalytic tests reveal that Na1/HMO has higher catalytic activity in low-temperature oxidation of HCHO than Ag1/HMO. X-ray photoelectron spectra and soft X-ray absorption spectra show that the surface lattice oxygen of Na1/HMO has a higher electronic density than that of Ag1/HMO, which is responsible for its higher catalytic efficiency in the oxidation of HCHO. This work could assist the rational design of cheap alkali metal catalysts for controlling the emissions of volatile organic compounds such as HCHO.

Alkali- and Sulfur-Resistant Tungsten-Based Catalysts for NOx Emissions Control.

The development of catalysts with simultaneous resistance to alkalis and sulfur poisoning is of great importance for efficiently controlling NOx emissions using the selective catalytic reduction of NOx with NH3 (SCR), because the conventional V2O5/WO3-TiO2 catalysts often suffer severe deactivation by alkalis. Here, we support V2O5 on a hexagonal WO3 (HWO) to develop a V2O5/HWO catalyst, which has exceptional resistance to alkali and sulfur poisoning in the SCR reactions. A 350 µmol g(-1) K(+) loading and the presence of 1,300 mg m(-3) SO2 do not almost influence the SCR activity of the V2O5/HWO catalyst, and under the same conditions, the conventional V2O5/WO3-TiO2 catalysts completely lost the SCR activity within 4 h. The strong resistance to alkali and sulfur poisoning of the V2O5/HWO catalysts mainly originates from the hexagonal structure of the HWO. The HWO allows the V2O5 to be highly dispersed on the external surfaces for catalyzing the SCR reactions and has the relatively smooth surfaces and the size-suitable tunnels specifically for alkalis' diffusion and trapping. This work provides a useful strategy to develop SCR catalysts with exceptional resistance to alkali and sulfur poisoning for controlling NOx emissions from the stationary source and the mobile source.

Status and Influencing Factors of Social Participation in Renal Transplantation Recipients: A Cross-Sectional Study From a Single Center in China.

BACKGROUND: To investigate the social participation (SP) of renal transplantation (RT) recipients and analyze the influencing factors. DESIGN: Cross-sectional study. METHODS: Data were collected from RT recipients reviewed within the Urology Outpatient Clinic of a tertiary class-A hospital in Hebei, China between October 2018 and October 2019. RESULTS: The total mean score of an SP questionnaire for RT recipients was 37.77 ± 2.74. The mean score per item in each dimension showed that the scores for leisure, activity, and voluntary participation in social life were the highest, indicating low participation. Educational level, household income, occupation, preoperative employment, creatinine level in the transplanted kidney, medication compliance, depression, and anxiety could explain 77% of the variation in the SP level. CONCLUSIONS: There are many factors affecting the SP levels of RT recipients. Clinicians should comprehensively evaluate RT recipients before and after surgery, formulate health education programs, and improve the SP level.

Comprehensive identification and characterization of lncRNAs and circRNAs reveal potential brown planthopper-responsive ceRNA networks in rice.

Brown planthopper (Nilaparvata lugens Stål, BPH) is one of the most destructive pests of rice. Non-coding RNA plays an important regulatory role in various biological processes. However, comprehensive identification and characterization of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in BPH-infested rice have not been performed. Here, we performed a genome-wide analysis of lncRNAs and circRNAs in BPH6-transgenic (resistant, BPH6G) and Nipponbare (susceptible, NIP) rice plants before and after BPH feeding (early and late stage) via deep RNA-sequencing. A total of 310 lncRNAs and 129 circRNAs were found to be differentially expressed. To reveal the different responses of resistant and susceptible rice to BPH herbivory, the potential functions of these lncRNAs and circRNAs as competitive endogenous RNAs (ceRNAs) were predicted and investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Dual-luciferase reporter assays revealed that miR1846c and miR530 were targeted by the lncRNAs XLOC_042442 and XLOC_028297, respectively. In responsive to BPH infestation, 39 lncRNAs and 21 circRNAs were predicted to combine with 133 common miRNAs and compete for miRNA binding sites with 834 mRNAs. These mRNAs predictably participated in cell wall organization or biogenesis, developmental growth, single-organism cellular process, and the response to stress. This study comprehensively identified and characterized lncRNAs and circRNAs, and integrated their potential ceRNA functions, to reveal the rice BPH-resistance network. These results lay a foundation for further study on the functions of lncRNAs and circRNAs in the rice-BPH interaction, and enriched our understanding of the BPH-resistance response in rice.

Integrated transcriptomics and metabolomics analysis provide insight into the resistance response of rice against brown planthopper.

Introduction: The brown planthopper (Nilaparvata lugens Stål, BPH) is one of the most economically significant pests of rice. The Bph30 gene has been successfully cloned and conferred rice with broad-spectrum resistance to BPH. However, the molecular mechanisms by which Bph30 enhances resistance to BPH remain poorly understood. Methods: Here, we conducted a transcriptomic and metabolomic analysis of Bph30-transgenic (BPH30T) and BPH-susceptible Nipponbare plants to elucidate the response of Bph30 to BPH infestation. Results: Transcriptomic analyses revealed that the pathway of plant hormone signal transduction enriched exclusively in Nipponbare, and the greatest number of differentially expressed genes (DEGs) were involved in indole 3-acetic acid (IAA) signal transduction. Analysis of differentially accumulated metabolites (DAMs) revealed that DAMs involved in the amino acids and derivatives category were down-regulated in BPH30T plants following BPH feeding, and the great majority of DAMs in flavonoids category displayed the trend of increasing in BPH30T plants; the opposite pattern was observed in Nipponbare plants. Combined transcriptomics and metabolomics analysis revealed that the pathways of amino acids biosynthesis, plant hormone signal transduction, phenylpropanoid biosynthesis and flavonoid biosynthesis were enriched. The content of IAA significantly decreased in BPH30T plants following BPH feeding, and the content of IAA remained unchanged in Nipponbare. The exogenous application of IAA weakened the BPH resistance conferred by Bph30. Discussion: Our results indicated that Bph30 might coordinate the movement of primary and secondary metabolites and hormones in plants via the shikimate pathway to enhance the resistance of rice to BPH. Our results have important reference significance for the resistance mechanisms analysis and the efficient utilization of major BPH-resistance genes.

Single-Cell RNA sequencing of leaf sheath cells reveals the mechanism of rice resistance to brown planthopper (Nilaparvata lugens).

The brown planthopper (BPH) (Nilaparvata lugens) sucks rice sap causing leaves to turn yellow and wither, often leading to reduced or zero yields. Rice co-evolved to resist damage by BPH. However, the molecular mechanisms, including the cells and tissues, involved in the resistance are still rarely reported. Single-cell sequencing technology allows us to analyze different cell types involved in BPH resistance. Here, using single-cell sequencing technology, we compared the response offered by the leaf sheaths of the susceptible (TN1) and resistant (YHY15) rice varieties to BPH (48 hours after infestation). We found that the 14,699 and 16,237 cells (identified via transcriptomics) in TN1 and YHY15 could be annotated using cell-specific marker genes into nine cell-type clusters. The two rice varieties showed significant differences in cell types (such as mestome sheath cells, guard cells, mesophyll cells, xylem cells, bulliform cells, and phloem cells) in the rice resistance mechanism to BPH. Further analysis revealed that although mesophyll, xylem, and phloem cells are involved in the BPH resistance response, the molecular mechanism used by each cell type is different. Mesophyll cell may regulate the expression of genes related to vanillin, capsaicin, and ROS production, phloem cell may regulate the cell wall extension related genes, and xylem cell may be involved in BPH resistance response by controlling the expression of chitin and pectin related genes. Thus, rice resistance to BPH is a complicated process involving multiple insect resistance factors. The results presented here will significantly promote the investigation of the molecular mechanisms underlying the resistance of rice to insects and accelerate the breeding of insect-resistant rice varieties.

Gut Microbiome Alterations Affect Glioma Development and Foxp3 Expression in Tumor Microenvironment in Mice.

Glioma is the most common malignant tumor of the central nervous system (CNS), with high degree of malignancy and poor prognosis. The gut microbiome (GM) is composed of microorganisms with different properties and functions, which play an important role in human physiology and biological activities. It has been proved that GM can affect the development of glioma through natural immunity, but whether GM can affect glioma through adaptive immunity and whether there are some microorganisms in the GM that may affect glioma growth still remain unclear. In our study, we evaluated the relationship between GM and glioma. We proved that (I) glioma growth can induce structural changes of mouse GM, including the decreased abundance of Bacteroidia and increased abundance of Firmicutes. (II) GM dysbiosis can downregulate Foxp3 expression in the brain and promote glioma growth. A balanced environment of GM can upregulate the expression of Foxp3 in the brain and delay the development of glioma. (III) The increased abundance of Bacteroidia is associated with accelerated glioma progression, while its decreased abundance is associated with delayed glioma progression, which may be one of the key microorganisms affecting glioma growth. This study is helpful to reveal the relationship between GM and glioma development and provide new ideas for adjuvant therapy of glioma.