Identification of the coexisting virus-derived siRNA in maize and rice infected by rice black-streaked dwarf virus.

Rice black-streaked dwarf virus is transmitted by small brown planthoppers, which causes maize rough dwarf disease and rice black-streaked dwarf disease. This virus leads to slow growth or death of the host plants. During the co-evolutionary arms race between viruses and plants, virus-derived small interfering RNAs challenge the plant's defense response and inhibit host immunity through the RNA silencing system. However, it is currently unknown if rice black-streaked dwarf virus can produce the same small interfering RNAs to mediate the RNA silencing in different infected species. In this study, four small RNA libraries and four degradome libraries were constructed by extracting total RNAs from the leaves of the maize (Zea mays) inbred line B73 and japonica rice (Oryza sativa) variety Nipponbare exposed to feeding by viruliferous and non-viruliferous small brown planthoppers. We analyzed the characteristics of small RNAs and explored virus-derived small interfering RNAs in small RNA libraries through high-throughput sequencing. On analyzing the characteristics of small RNA, we noted that the size distributions of small RNAs were mainly 24-nt (19.74%-62.00%), whereas those of virus-derived small interfering RNAs were mostly 21-nt (41.06%-41.87%) and 22-nt (39.72%-42.26%). The 5'-terminal nucleotides of virus-derived small interfering RNAs tended to be adenine or uracil. Exploring the distribution of virus-derived small interfering RNAs hot spots on the viral genome segments revealed that the frequency of hot spots in B73 was higher than those in Nipponbare. Meanwhile, hotspots in the S9 and S10 virus genome segments were distributed similarly in both hosts. In addition, the target genes of small RNA were explored by degradome sequencing. Analyses of the regulatory pathway of these target genes unveiled that viral infection affected the ribosome-related target genes in maize and target genes in metabolism and biosynthesis pathways in rice. Here, 562 and 703 virus-derived small interfering RNAs were separately obtained in maize and rice, and 73 virus-derived small interfering RNAs named as co-vsiRNAs were detected in both hosts. Stem-loop PCR and RT-qPCR confirmed that co-vsiRNA 3.1 and co-vsiRNA 3.5 derived from genome segment S3 simultaneously play a role in maize and rice and inhibited host gene expression. The study revealed that rice black-streaked dwarf virus can produce the same small interfering RNAs in different species and provides a new direction for developing the new antiviral strategies.

Gene pyramiding of ZmGLK36 and ZmGDIα-hel for rough dwarf disease resistance in maize.

Maize rough dwarf disease (MRDD) caused by pathogenic viruses in the genus Fijivirus in the family Reoviridae is one of the most destructive diseases in maize. The pyramiding of effective resistance genes into maize varieties is a potential approach to reduce the damage resulting from the disease. Two major quantitative trait loci (QTLs) (qMrdd2 and qMrdd8) have been previously identified. The resistance genes ZmGLK36 and ZmGDIα-hel have also been cloned with the functional markers Indel-26 and IDP25K, respectively. In this study, ZmGLK36 and ZmGDIα-hel were introgressed to improve MRDD resistance of maize lines (Zheng58, Chang7-2, B73, Mo17, and their derived hybrids Zhengdan958 and B73 × Mo17) via marker-assisted selection (MAS). The converted lines and their derived hybrids, carrying one or two genes, were evaluated for MRDD resistance using artificial inoculation methods. The double-gene pyramiding lines and their derived hybrids exhibited increased resistance to MRDD compared to the monogenic lines and the respective hybrids. The genetic backgrounds of the converted lines were highly similar (90.85-98.58%) to the recurrent parents. In addition, agronomic trait evaluation demonstrated that pyramiding lines with one or two genes and their derived hybrids were not significantly different from the recurrent parents and their hybrids under nonpathogenic stress, including period traits (tasseling, pollen shedding, and silking), yield traits (ear length, grain weight per ear and 100-kernel weight) and quality traits (protein and starch content). There were differences in plant architecture traits between the improved lines and their hybrids. This study illustrated the successful development of gene pyramiding for improving MRDD resistance by advancing the breeding process. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01466-9.

ZmADF5, a Maize Actin-Depolymerizing Factor Conferring Enhanced Drought Tolerance in Maize.

Drought stress is seriously affecting the growth and production of crops, especially when agricultural irrigation still remains quantitatively restricted in some arid and semi-arid areas. The identification of drought-tolerant genes is important for improving the adaptability of maize under stress. Here, we found that a new member of the actin-depolymerizing factor (ADF) family; the ZmADF5 gene was tightly linked with a consensus drought-tolerant quantitative trait locus, and the significantly associated signals were detected through genome wide association analysis. ZmADF5 expression could be induced by osmotic stress and the application of exogenous abscisic acid. Its overexpression in Arabidopsis and maize helped plants to keep a higher survival rate after water-deficit stress, which reduced the stomatal aperture and the water-loss rate, as well as improved clearance of reactive oxygen species. Moreover, seventeen differentially expressed genes were identified as regulated by both drought stress and ZmADF5, four of which were involved in the ABA-dependent drought stress response. ZmADF5-overexpressing plants were also identified as sensitive to ABA during the seed germination and seedling stages. These results suggested that ZmADF5 played an important role in the response to drought stress.

A transcription factor ZmGLK36 confers broad resistance to maize rough dwarf disease in cereal crops.

Maize rough dwarf disease (MRDD), caused by maize rough dwarf virus (MRDV) or rice black-streaked dwarf virus (RBSDV), seriously threatens worldwide production of all major cereal crops, including maize, rice, wheat and barley. Here we report fine mapping and cloning of a previously reported major quantitative trait locus (QTL) (qMrdd2) for RBSDV resistance in maize. Subsequently, we show that qMrdd2 encodes a G2-like transcription factor named ZmGLK36 that promotes resistance to RBSDV by enhancing jasmonic acid (JA) biosynthesis and JA-mediated defence response. We identify a 26-bp indel located in the 5' UTR of ZmGLK36 that contributes to differential expression and resistance to RBSDV in maize inbred lines. Moreover, we show that ZmDBF2, an AP2/EREBP family transcription factor, directly binds to the 26-bp indel and represses ZmGLK36 expression. We further demonstrate that ZmGLK36 plays a conserved role in conferring resistance to RBSDV in rice and wheat using transgenic or marker-assisted breeding approaches. Our results provide insights into the molecular mechanisms of RBSDV resistance and effective strategies to breed RBSDV-resistant cereal crops.

Health-Related Quality of Life With Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients With Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma From CheckMate 649.

PURPOSE: In CheckMate 649, first-line nivolumab plus chemotherapy prolonged overall survival versus chemotherapy in patients with advanced/metastatic non-human epidermal growth factor receptor 2 (HER2)-positive gastric/gastroesophageal junction cancer (GC/GEJC) or esophageal adenocarcinoma (EAC). We present exploratory patient-reported outcomes (PROs). METHODS: In patients (N = 1,581) concurrently randomly assigned 1:1 to nivolumab plus chemotherapy or chemotherapy and in those with tumor PD-L1 expression at a combined positive score (CPS) of ≥5, health-related quality of life (HRQoL) was assessed using the EQ-5D and Functional Assessment of Cancer Therapy-Gastric (FACT-Ga), which included the FACT-General (FACT-G) and Gastric Cancer subscale (GaCS). The FACT-G GP5 item assessed treatment-related symptom burden. Longitudinal changes in HRQoL were assessed using mixed models for repeated measures in the PRO analysis population (randomly assigned patients with baseline and ≥1 postbaseline assessments). Time to symptom or definitive deterioration analyses were also conducted. RESULTS: In the PRO analysis population (n = 1,360), PRO questionnaire completion rates were mostly >80% during treatment. Patient-reported symptom burden was not increased with nivolumab plus chemotherapy versus chemotherapy. Mean improved changes from baseline were greater with nivolumab plus chemotherapy versus chemotherapy for FACT-Ga total, GaCS, and EQ-5D visual analog scale in patients with a CPS of ≥5; results were similar for the overall PRO analysis population. In CPS ≥5 and all randomly assigned populations, nivolumab plus chemotherapy reduced the risk of symptom deterioration versus chemotherapy, on the basis of FACT-Ga total score and GaCS; time to definitive deterioration was longer, and the risk of definitive deterioration in HRQoL was reduced with nivolumab plus chemotherapy across EQ-5D and most FACT-Ga measures (hazard ratio [95% CI] <1). CONCLUSION: Compared with chemotherapy alone, first-line nivolumab plus chemotherapy showed stable or better on-treatment HRQoL in patients with advanced/metastatic non-HER2-positive GC/GEJC/EAC and also showed decreased risk of definitive HRQoL deterioration.

Toxic response of antimony in the Comamonas testosteroni and its application in soil antimony bioremediation.

Antimony (Sb) is toxic to ecosystems and potentially to public health via its accumulation in the food chain. Bioavailability and toxicity of Sb have been reduced using various methods for the remediation of Sb-contaminated soil in most studies. However, Sb-contaminated soil remediation by microbial agents has been rarely evaluated. In this study, we evaluated the potential for the use of Comamonas testosteroni JL40 in the bioremediation of Sb-contamination. Strain JL40 immobilized more than 30 % of the Sb(III) in solution and oxidized over 18 % to Sb(V) for detoxification. Meanwhile, strain JL40 responds to Sb toxicity through such as Sb efflux, intracellular accumulation, biofilm production, and scavenging of reactive oxygen species (ROS), etc. The results of the pot experiment showed the average Sb content of the brown rice was decreased by 59.1%, 38.8%, and 48.4%, for 1.8, 50, and 100 mg/kg Sb spiked soils, respectively. In addition, the results of plant, soil enzyme activity, and rice agronomic trait observations showed that the application of strain JL40 could maintain the health of plants and soil and improve rice production. The single-step and sequential extraction of Sb from rhizosphere soil showed that strain JL40 also plays a role in Sb immobilization and oxidation in the soil environment. During rice potted cultivation, bacterial community analysis and plate counting showed that the strain JL40 could still maintain 103 CFU/g after 30 days of inoculation. With phenotypic and differential proteomics analysis, strain JL40 conferred Sb(III) tolerance by a combination of immobilization, oxidation, efflux and scavenging of ROS, etc. Our study demonstrates the application of Sb-immobilizing and oxidizing bacteria to lower soil Sb and reduce accumulation of Sb in rice. Our results provide guidance for bacterial remediation of Sb-contaminated soil.

Sphingobium nicotianae sp. nov., isolated from tobacco soil.

Bacterial strain H33T was isolated from tobacco plant soil and was characterized using a polyphasic taxonomy approach. Strain H33T was a Gram-stain-negative, rod-shaped, non-motile and strictly aerobic bacterium. Phylogenetic analyses based on 16S rRNA gene sequences and coding sequences of the up-to-date bacterial core gene set (92 protein clusters) indicated that H33T belongs to the genus Sphingobium. Strain H33T showed the highest 16S rRNA gene sequence similarity to Sphingobium xanthum NL9T (97.2%) and showed 72.3-80.6 % average nucleotide identity and 19.7-29.2 % digital DNA-DNA hybridization identity with the strains of other species of the genus Sphingobium. Strain H33T grew optimally at 30°C, pH 7 and could tolerate 0.5 % (w/v) NaCl. The isoprenoid quinones were ubiquinone-9 (64.1%) and ubiquinone-10 (35.9%). Spermidine was the major polyamine. The major fatty acids of H33T were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The polar lipid profile consisted of a mixture of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, sphingoglycolipid, two unidentified lipids, two unidentified glycolipids, two unidentified aminoglycolipids and an unidentified phospholipid. The genomic DNA G+C content of H33T was 64.9 mol%. Based on the phylogenetic and phenotypic data, H33T was considered a representative of a novel species in the genus Sphingobium. We propose the name Sphingobium nicotianae sp. nov., with H33T (=CCTCC AB 2022073T=LMG 32569T) as the type strain.

Croceibacterium selenioxidans sp. nov., isolated from seleniferous soil.

A Gram-negative, aerobic bacterial strain, designated LX-88T, was isolated from seleniferous soil in Enshi, Hubei Province, PR China. Strain LX-88Toxidized elemental selenium to selenite, and produced carotenoids but not bacteriochlorophyll. The isolate grew optimally at 28 °C, pH 8.0 and with 0.5 % (w/v) NaCl. Phylogenetic analysies of the organism's 16S rRNA and bacterial core gene set sequences indicated that LX-88T belongs to the genus Croceibacterium, and has the highest degree of 16S rRNA gene sequence similarity to Croceibacterium soli MN-1T (97.4 %). The LX-88T genome was 3.4 Mbp and had a G+C content of 63.6 mol%. The average nucleotide identity and digital DNA-DNA hybridization values showed low relatedness (below 95 and 70 %, respectively) between strain LX-88T and other strains in the genus Croceibacterium. Ubiquinone-10 was the predominant quinone. The polar lipid profile was dominated by diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, sphingoglycolipid, an unidentified aminolipid, an unidentified phospholipid and an unidentified lipid. The major fatty acid was summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). These physiological and biochemical tests facilitated the differentiation of strain LX-88T from other members of the genus Croceibacterium. The results of this multifaceted taxonomic study indicate that strain LX-88T represents a novel species in the genus Croceibacterium, for which the name Croceibacterium selenioxidans sp. nov. is proposed. The type strain is LX-88T (=MCCC 1K08007T=LMG 32570T).

A plain language summary of the CheckMate 649 study: nivolumab in combination with chemotherapy compared to chemotherapy alone for untreated advanced or metastatic cancer of the stomach or esophagus.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of the 1-year results of a clinical research study known as CheckMate 649 published in The Lancet in June 2021. The 2-year results on the participants' health and overall quality of life from the same study are in a second publication in Nature in March 2022. Until recently, chemotherapy was the only first treatment option for people with advanced or metastatic gastroesophageal adenocarcinoma who had not been treated before. Patients receiving chemotherapy lived on average for less than 1 year. Nivolumab is an immunotherapy that works by activating a person's immune system to fight back against cancer cells. The goal of CheckMate 649 was to find out if the combination of nivolumab and chemotherapy would help patients with advanced or metastatic gastroesophageal adenocarcinoma live longer and without their cancer getting worse. WHAT WERE THE RESULTS?: Results from the final analysis are reported here. Of 1581 people who took part in the study, 789 received nivolumab and chemotherapy and 792 received chemotherapy. Researchers found that, on average, participants who received nivolumab and chemotherapy lived longer overall than those who received chemotherapy alone. The length of time participants lived without their cancer getting worse was also longer on average with nivolumab and chemotherapy than chemotherapy treatment alone. However, more participants in the nivolumab and chemotherapy group had side effects than those in the chemotherapy group. The three most common side effects in both types of treatment were nausea (urge to vomit), diarrhea and peripheral neuropathy. Participants who received nivolumab and chemotherapy had a lower risk of their cancer symptoms worsening and reported that they were 'less bothered' from side effects of treatment than those receiving chemotherapy alone. WHAT DO THE RESULTS MEAN?: The nivolumab and chemotherapy combination is considered a new standard treatment option and is approved in several countries as a treatment for adults who have not been treated before for their advanced or metastatic gastroesophageal cancer based on results from CheckMate 649. Clinical Trial Registration: NCT02872116 (ClinicalTrials.gov).

Microorganisms@aMIL-125 (Ti): An Amorphous Metal-Organic Framework Induced by Microorganisms and Their Applications.

Amorphous metal-organic framework (aMOF)-based materials have attracted considerable attention as an emerging class of nanomaterials. Herein, novel microorganisms@aMIL-125 (Ti) composites including yeast@aMIL-125 (Ti), PCC 6803@aMIL-125 (Ti), and Escherichia coli@aMIL-125 (Ti) composites were respectively synthesized by self-assembling aMOFs on the microorganisms' surface. The functional groups on the microorganisms' surface induced structural defects and participated in the formation of aMIL-125 (Ti) composites. Finally, the application of microorganisms@aMIL-125 (Ti) composites for the removal of glyphosate from aqueous solution was selected as a model reaction to illustrate their potential for environmental protection. The present method is not only economical but also has other advantages including ease of operation, environmentally friendly assay, and high adsorption. The maximum adsorption capacity of aMIL-125 (Ti) was 1096.25 mg g-1, which was 1.74 times that of crystalline MIL-125 (Ti). Therefore, the microorganisms@aMOFs composites will have broad application prospects in energy storage, drug delivery, catalysis, adsorbing toxic substances, sensing, encapsulating and delivering enzymes, and in other fields.

Dual-responsive ratiometric fluorescent sensor for tetracyclines detection based on europium-decorated copper nanoclusters.

Development of accurate and efficient TCs residue analysis methods is of great significance for the protection of environment, food safety and public health. Herein, a dual-responsive ratiometric fluorescence sensor being capable of simple and sensitive detection of tetracycline (TC) was presented, which was constructed by immobilizing europium ions (Eu3+) onto the mercaptopropionic acid stabilized copper nanoclusters (MPA-Cu NCs). In the presence of TC, the red fluorescence of Eu3+ was enhanced through antenna effect (AE), while the green fluorescence of MPA-Cu NCs was quenched through internal filter effect (IFE), leading to an obvious fluorescence color evolution from green to red for the probe solution. In addition to successful design of a smartphone-assisted colorimetric analysis platform for portable detection, a logic gate device capable of intelligently monitoring TC concentration is also designed.

Genotypic variation in field-grown maize eliminates trade-offs between resistance, tolerance and growth in response to high pressure from the Asian corn borer.

Insect herbivory challenges plant survival, and coordination of the interactions between growth, herbivore resistance/tolerance is a key problem faced by plants. Based on field experiments into resistance to the Asian corn borer (ACB, Ostrinia furnacalis), we selected 10 inbred maize lines, of which five were resistant and five were susceptible to ACB. We conducted ACB larval bioassays, analysed defensive chemicals, phytohormones, and relative gene expression using RNA-seq and qPCR as well as agronomic traits, and found resistant lines had weaker inducibility, but were more resistant after ACB attack than susceptible lines. Resistance was related to high levels of major benzoxazinoids, but was not related to induced levels of JA or JA-Ile. Following combination analyses of transcriptome, metabolome and larval performance data, we discovered three benzoxazinoids biosynthesis-related transcription factors, NAC60, WRKY1 and WRKY46. Protoplast transformation analysis suggested that these may regulate maize defence-growth trade-offs by increasing levels of benzoxazinoids, JA and SA but decreasing IAA. Moreover, the resistance/tolerance-growth trade-offs were not observed in the 10 lines, and genotype-specific metabolic and genetic features probably eliminated the trade-offs. This study highlights the possibility of breeding maize varieties simultaneously with improved defences and higher yield under complex field conditions.

Pathogenicity Variation in Two Genomes of Cercospora Species Causing Gray Leaf Spot in Maize.

The gray leaf spots caused by Cercospora spp. severely affect the yield and quality of maize. However, the evolutionary relation and pathogenicity variation between species of the Cercospora genus is largely unknown. In this study, we constructed high-quality reference genomes by nanopore sequencing two Cercospora species, namely, C. zeae-maydis and C. zeina, with differing pathogenicity, collected from northeast (Liaoning [LN]) and southeast (Yunnan [YN]) China, respectively. The genome size of C. zeae-maydis-LN is 45.08 Mb, containing 10,839 annotated genes, whereas that of Cercospora zeina-YN is 42.18 Mb, containing 10,867 annotated genes, of which approximately 86.58% are common in the two species. The difference in their genome size is largely attributed to increased long terminal repeat retrotransposons of 3.8 Mb in total length in C. zeae-maydis-LN. There are 41 and 30 carbohydrate-binding gene subfamilies identified in C. zeae-maydis-LN and C. zeina-YN, respectively. A higher number of carbohydrate-binding families found in C. zeae-maydis-LN, and its unique CBM4, CBM37, and CBM66, in particular, may contribute to variation in pathogenicity between the two species, as the carbohydrate-binding genes are known to encode cell wall-degrading enzymes. Moreover, there are 114 and 107 effectors predicted, with 47 and 46 having unique potential pathogenicity in C. zeae-maydis-LN and C. zeina-YN, respectively. Of eight effectors randomly selected for pathogenic testing, five were found to inhibit cell apoptosis induced by Bcl-2-associated X. Taken together, our results provide genomic insights into variation in pathogenicity between C. zeae-maydis and C. zeina. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric, gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis.

First-line chemotherapy for advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction cancer (GC/GEJC) has poor median overall survival (OS; <1 year). We report efficacy and safety results from Chinese patients in the phase III global CheckMate 649 study of nivolumab plus chemotherapy vs chemotherapy for the first-line treatment of GC/GEJC/esophageal adenocarcinoma (EAC). Chinese patients with previously untreated advanced or metastatic GC/GEJC/EAC were randomized to receive nivolumab (360 mg Q3W or 240 mg Q2W) plus chemotherapy (XELOX [capecitabine and oxaliplatin] Q3W or FOLFOX [oxaliplatin, leucovorin and 5-fluorouracil] Q2W), nivolumab plus ipilimumab (not reported) or chemotherapy alone. OS, blinded independent central review-assessed progression-free survival (PFS), objective response rate (ORR), duration of response (DOR) and safety are reported. Of 1581 patients enrolled and randomized, 208 were Chinese. In these patients, nivolumab plus chemotherapy resulted in clinically meaningful improvement in median OS (14.3 vs 10.2 months; HR 0.61 [95% CI: 0.44-0.85]), median PFS (8.3 vs 5.6 months; HR 0.57 [95% CI: 0.40-0.80]), ORR (66% vs 45%) and median DOR (12.2 vs 5.6 months) vs chemotherapy, respectively. The safety profile was acceptable, with no new safety signals observed. Consistent with results from the global primary analysis of CheckMate 649, nivolumab plus chemotherapy demonstrated a clinically meaningful improvement in OS and PFS and higher response rate vs chemotherapy and an acceptable safety profile in Chinese patients. Nivolumab plus chemotherapy represents a new standard first-line treatment for Chinese patients with non-HER2-positive advanced GC/GEJC/EAC.

Microbial oxidation of organic and elemental selenium to selenite.

Selenium (Se) is an essential trace element for life. Se reduction has attracted much attention in the microbial Se cycle, but there is less evidence for Se oxidation. In particular, it is unknown whether microorganisms oxidise organic Se(-II). In this study, four strains of bacteria, namely Dyella spp. LX-1 and LX-66, and Rhodanobacter spp. LX-99 and LX-100, isolated from seleniferous soil, were involved in the oxidation of selenomethionine (SeMet), selenocystine (SeCys2), selenourea and Se(0) to selenite (Se(IV)) in pure cultures. The oxidation rates of organic Se were more rapidly than those of Se(0) in liquid media. Then Se(0) and SeMet were used as examples, microbial oxidation was the predominant process for both additional Se(0) and SeMet in sterilised alkaline or acidic soils. The Se(IV) concentrations were significantly higher at pH 8.56 than at pH 5.25. In addition, water-soluble Se (SOLSe) and exchangeable and carbonate-bound Se (EXC-Se) fractions increased dramatically with these four Se-oxidising bacteria in unsterilised seleniferous soil. To our knowledge, this is the first study to find that various bacteria are involved in the oxidation of organic Se to Se oxyanions, bridging the gap of Se redox in the Se biogeochemical cycle.

Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer.

Standard first-line chemotherapy results in disease progression and death within one year in most patients with human epidermal growth factor receptor 2 (HER2)-negative gastro-oesophageal adenocarcinoma1-4. Nivolumab plus chemotherapy demonstrated superior overall survival versus chemotherapy at 12-month follow-up in gastric, gastro-oesophageal junction or oesophageal adenocarcinoma in the randomized, global CheckMate 649 phase 3 trial5 (programmed death ligand-1 (PD-L1) combined positive score ≥5 and all randomized patients). On the basis of these results, nivolumab plus chemotherapy is now approved as a first-line treatment for these patients in many countries6. Nivolumab and the cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab have distinct but complementary mechanisms of action that contribute to the restoration of anti-tumour T-cell function and induction of de novo anti-tumour T-cell responses, respectively7-11. Treatment combining 1 mg kg-1 nivolumab with 3 mg kg-1 ipilimumab demonstrated clinically meaningful anti-tumour activity with a manageable safety profile in heavily pre-treated patients with advanced gastro-oesophageal cancer12. Here we report both long-term follow-up results comparing nivolumab plus chemotherapy versus chemotherapy alone and the first results comparing nivolumab plus ipilimumab versus chemotherapy alone from CheckMate 649. After the 24.0-month minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in overall survival versus chemotherapy alone in patients with PD-L1 combined positive score ≥5 (hazard ratio 0.70; 95% confidence interval 0.61, 0.81) and all randomized patients (hazard ratio 0.79; 95% confidence interval 0.71, 0.88). Overall survival in patients with PD-L1 combined positive score ≥ 5 for nivolumab plus ipilimumab versus chemotherapy alone did not meet the prespecified boundary for significance. No new safety signals were identified. Our results support the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastro-oesophageal adenocarcinoma.

Using the dominant mutation gene Ae1-5180 (amylose extender) to develop high-amylose maize.

Maize amylose is a type of high value-added starch used for medical, food, and chemical applications. Mutations in the starch branching enzyme (SBEIIb), with recessive ae (amylose extender) and dominant Ae1-5180 alleles, are the primary way to improve maize endosperm amylose content (AC). However, studies on Ae1-5180 mutation are scarce, and its roles in starch synthesis and breeding potential are unclear. We found that the AC of the Ae1-5180 mutant was 47.23%, and its kernels were tarnished and glassy and are easily distinguished from those of the wild type (WT), indicating that the dominant mutant has the classical characteristics of the ae mutant. Starch granules of Ae1-5180 became smaller, and higher in amount with irregular shape. The degree of amylopectin polymerisation changed to induce an increase in starch thermal stability. Compared with WT, the activity of granule-bound starch synthase and starch synthase was higher in early stages and lower in later stages, and other starch synthesis enzymes decreased during kernel development in the Ae1-5180 mutant. We successfully developed a marker (mu406) for the assisted selection of 17 Ae1-5180 near isogenic lines (NILs) according to the position of insertion of the Mu1 transposon in the SBEIIb promoter of Ae1-5180. JH214/Ae1-5180, CANS-1/Ae1-5180, CA240/Ae1-5180, and Z1698/Ae1-5180 have high breeding application potential with their higher AC (> 40%) and their 100-kernel weight decreased to < 25% compared to respective recurrent parents. Therefore, using the dominant Ae1-5180 mutant as a donor can detect the kernel phenotype and AC of Ae1-5180-NILs in advance, thereby accelerating the high-amylose breeding process. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01323-7.

Reducing cadmium in rice using metallothionein surface-engineered bacteria WH16-1-MT.

Cadmium (Cd) accumulation in rice grains poses a health risk for humans. In this study, a bacterium, Alishewanella sp. WH16-1-MT, was engineered to express metallothionein on the cell surface. Compared with the parental WH16-1 strain, Cd2+ adsorption efficiency of WH16-1-MT in medium was increased from 1.2 to 2.6 mg/kg dry weight. The WH16-1-MT strain was then incubated with rice in moderately Cd-contaminated paddy soil. Compared with WH16-1, inoculation with WH16-1-MT increased plant height, panicle length and thousand-kernel weight, and decreased the levels of ascorbic acid and glutathione and the activity of peroxidase. Compared with WH16-1, WH16-1-MT inoculation significantly reduced the concentrations of Cd in brown rice, husks, roots and shoots by 44.0 %, 45.5 %, 36.1 % and 47.2 %, respectively. Moreover, inoculation with WH16-1-MT reduced the bioavailability of Cd in soil, with the total Cd proportion in oxidizable and residual states increased from 29 % to 32 %. Microbiome analysis demonstrated that the addition of WH16-1-MT did not significantly alter the original bacterial abundance and community structure in soil. These results indicate that WH16-1-MT can be used as a novel microbial treatment approach to reduce Cd in rice grown in moderately Cd-contaminated paddy soil.

Identification and Fine-Mapping of a Novel QTL, qMrdd2, That Confers Resistance to Maize Rough Dwarf Disease.

Maize rough dwarf disease (MRDD) is caused by a virus and seriously affects maize quality and yield worldwide. MRDD can be most effectively controlled with disease-resistant hybrids of corn. Here, MRDD-resistant (Qi319) and -susceptible (Ye478) parental inbred maize lines and their 314 recombinant inbred lines (RILs) that were derived from a cross between them were evaluated across three environments. A stable resistance QTL, qMrdd2, was identified and mapped using best linear unbiased prediction (BLUP) values to a 0.55-Mb region between the markers MK807 and MK811 on chromosome 2 (B73 RefGen_v3) and was found to explain 8.6 to 11.0% of the total phenotypic variance in MRDD resistance. We validated the effect of qMrdd2 using a chromosome segment substitution line (CSSL) that was derived from a cross between maize inbred Qi319 as the MRDD resistance donor and Ye478 as the recipient. Disease severity index of the CSSL haplotype II harboring qMrdd2 was significantly lower than that of the susceptible parent Ye478. Subsequently, we fine-mapped qMrdd2 to a 315-kb region flanked by the markers RD81 and RD87, thus testing recombinant-derived progeny using selfed backcrossed families. In this study, we identified a novel QTL for MRDD resistance by combining the RIL and CSSL populations, thus providing important genetic information that can be used for breeding MRDD-resistant varieties of maize.