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The cotton bollworm Helicoverpa armigera , is one of the world’s major pest of agriculture, feeding on over 300 hosts in 68 plant families. Resistance cases to most insecticide classes have been reported for this insect. Management of this pest in agroecosystems relies on a better understanding of how it copes with phytochemical or synthetic toxins. We have used genome editing to knock out a cluster of nine P450 genes and show that this significantly reduces the survival rate of the insect when exposed to two classes of host plant chemicals and two classes of insecticides. Functional expression of all members of this gene cluster identified the P450 enzymes capable of metabolism of these xenobiotics. The CRISPR-Cas9-based reverse genetics approach in conjunction with in vitro metabolism can rapidly identify the contributions of insect P450s in xenobiotic detoxification and serve to identify candidate genes for insecticide resistance. Cotton bollworm is an important agricultural pest with widespread resistance to insecticides. Here Wang et al . identifies CYP6AEs from cotton bollworm involved in detoxifying plant toxins and chemical insecticides through the CRISPR-Cas9-based reverse genetics approach in conjunction with in vitro metabolism.

Oxygen, one of the most abundant elements on Earth, often forms an undesired interstitial impurity or ceramic phase (such as an oxide particle) in metallic materials. Even when it adds strength, oxygen doping renders metals brittle 1 – 3 . Here we show that oxygen can take the form of ordered oxygen complexes, a state in between oxide particles and frequently occurring random interstitials. Unlike traditional interstitial strengthening 4 , 5 , such ordered interstitial complexes lead to unprecedented enhancement in both strength and ductility in compositionally complex solid solutions, the so-called high-entropy alloys (HEAs) 6 – 10 . The tensile strength is enhanced (by 48.5 ± 1.8 per cent) and ductility is substantially improved (by 95.2 ± 8.1 per cent) when doping a model TiZrHfNb HEA with 2.0 atomic per cent oxygen, thus breaking the long-standing strength–ductility trade-off 11 . The oxygen complexes are ordered nanoscale regions within the HEA characterized by (O, Zr, Ti)-rich atomic complexes whose formation is promoted by the existence of chemical short-range ordering among some of the substitutional matrix elements in the HEAs. Carbon has been reported to improve strength and ductility simultaneously in face-centred cubic HEAs 12 , by lowering the stacking fault energy and increasing the lattice friction stress. By contrast, the ordered interstitial complexes described here change the dislocation shear mode from planar slip to wavy slip, and promote double cross-slip and thus dislocation multiplication through the formation of Frank–Read sources (a mechanism explaining the generation of multiple dislocations) during deformation. This ordered interstitial complex-mediated strain-hardening mechanism should be particularly useful in Ti-, Zr- and Hf-containing alloys, in which interstitial elements are highly undesirable owing to their embrittlement effects, and in alloys where tuning the stacking fault energy and exploiting athermal transformations 13 do not lead to property enhancement. These results provide insight into the role of interstitial solid solutions and associated ordering strengthening mechanisms in metallic materials. Ordered oxygen complexes in high-entropy alloys enhance both strength and ductility in these compositionally complex solid solutions.

Evolution of pest resistance reduces the efficacy of insecticidal proteins from the gram-positive bacterium Bacillus thuringiensis (Bt) used widely in sprays and transgenic crops. Better understanding of the genetic basis of resistance is needed to more effectively monitor, manage, and counter pest resistance to Bt toxins. Here we used CRISPR/Cas9 gene editing to clarify the genetics of Bt resistance and the associated effects on susceptibility to other microbial insecticides in one of the world's most damaging pests, the cotton bollworm (Helicoverpa armigera). We discovered that CRISPR-mediated knockouts of ATP-binding cassette (ABC) transporter genes HaABCC2 and HaABCC3 together caused >15,000-fold resistance to Bt toxin Cry1Ac, whereas knocking out either HaABCC2 or HaABCC3 alone had little or no effect. Inheritance of resistance was autosomal and recessive. Bioassays of progeny from interstrain crosses revealed that one wild type allele of either HaABCC2 or HaABCC3 is sufficient to sustain substantial susceptibility to Cry1Ac. In contrast with previous results, susceptibility to two insecticides derived from bacteria other than Bt (abamectin and spinetoram), was not affected by knocking out HaABCC2, HaABCC3, or both. The results here provide the first evidence that either HaABCC2 or HaABCC3 protein is sufficient to confer substantial susceptibility to Cry1Ac. The functional redundancy of these two proteins in toxicity of Cry1Ac to H. armigera is expected to reduce the likelihood of field-evolved resistance relative to disruption of a toxic process where mutations affecting a single protein can confer resistance.

Combining four years of field data with computer modeling reveals that development of resistance to Bacillus thuringiensis insecticidal proteins (Bt) in cotton bollworm can be delayed by refuges of non-Bt host plants other than cotton, but that these so-called ‘natural refuges’ are not as effective as non-Bt cotton refuges. The ‘natural refuge strategy” for delaying insect resistance to transgenic cotton that produces insecticidal proteins from Bacillus thuringiensis (Bt) relies on refuges of host plants other than cotton that do not make Bt toxins. We tested this widely adopted strategy by comparing predictions from modeling with data from a four-year field study of cotton bollworm ( Helicoverpa armigera ) resistance to transgenic cotton producing Bt toxin Cry1Ac in six provinces of northern China. Bioassay data revealed that the percentage of resistant insects increased from 0.93% in 2010 to 5.5% in 2013. Modeling predicted that the percentage of resistant insects would exceed 98% in 2013 without natural refuges, but would increase to only 1.1% if natural refuges were as effective as non-Bt cotton refuges. Therefore, the results imply that natural refuges delayed resistance, but were not as effective as an equivalent area of non-Bt cotton refuges. The percentage of resistant insects with nonrecessive inheritance of resistance increased from 37% in 2010 to 84% in 2013. Switching to Bt cotton producing two or more toxins and integrating other control tactics could slow further increases in resistance.

The evolution of insecticide resistance represents a global constraint to agricultural production. Because of the extreme genetic diversity found in insects and the large numbers of genes involved in insecticide detoxification, better tools are needed to quickly identify and validate the involvement of putative resistance genes for improved monitoring, management, and countering of field-evolved insecticide resistance. The avermectins, emamectin benzoate (EB) and abamectin are relatively new pesticides with reduced environmental risk that target a wide number of insect pests, including the beet armyworm, Spodoptera exigua , an important global pest of many crops. Unfortunately, field resistance to avermectins recently evolved in the beet armyworm, threatening the sustainable use of this class of insecticides. Here, we report a high-quality chromosome-level assembly of the beet armyworm genome and use bulked segregant analysis (BSA) to identify the locus of avermectin resistance, which mapped on 15–16 Mbp of chromosome 17. Knockout of the CYP9A186 gene that maps within this region by CRISPR/Cas9 gene editing fully restored EB susceptibility, implicating this gene in avermectin resistance. Heterologous expression and in vitro functional assays further confirm that a natural substitution (F116V) found in the substrate recognition site 1 (SRS1) of the CYP9A186 protein results in enhanced metabolism of EB and abamectin. Hence, the combined approach of coupling gene editing with BSA allows for the rapid identification of metabolic resistance genes responsible for insecticide resistance, which is critical for effective monitoring and adaptive management of insecticide resistance.

Proteolytic processing of Bacillus thuringiensis (Bt) Cry protoxins by insect midgut proteases is critical to their insecticidal activities against target insects. Although transgenic Bt cotton expressing Cry1Ac and Cry2Ab proteins have been widely used for control of the cotton bollworm (Helicoverpa armigera) in the field, the proteolytic cleavage sites in the two protoxins targeted by H. armigera midgut proteases are still not clear. In this study, the proteolysis of Cry1Ac and Cry2Ab protoxins by midgut juice prepared from midgut tissue of H. armigera larvae was investigated. Cleavage of Cry1Ac protoxin by midgut proteases formed a major protein fragment of ~65 kDa, and N-terminal sequencing revealed that cleavage occurred at Arg28 in the fore-end of helix α-1 in domain I of Cry1Ac. Cleavage of Cry2Ab protoxin by midgut juice proteases produced a major protein fragment of ~50 kDa, and the cleavage occurred at Arg139 between helices α-3 and α-4 in domain I of Cry2Ab. The amino acids Arg28 of Cry1Ac and Arg139 of Cry2Ab were predicted as putative trypsin cleavage sites. Bioassay data showed that the toxicities (LC50s) of Cry1Ac and Cry2Ab protoxins were equivalent to those of their respective midgut juice-activated toxins in the susceptible SCD strain of H. armigera. Identification of the exact sites of N-terminal activation of Cry1Ac and Cry2Ab protoxins will provide a basis for a better understanding of the mode of action and resistance mechanisms based on aberrant activation of these protoxins in H. armigera.

Base editing technology is an ideal solution for treating pathogenic single-nucleotide variations (SNVs). No gene editing therapy has yet been approved for eye diseases, such as retinitis pigmentosa (RP). Here, we show, in the rd10 mouse model, which carries an SNV identified as an RP-causing mutation in human patients, that subretinal delivery of an optimized dual adeno-associated virus system containing the adenine base editor corrects the pathogenic SNV in the neuroretina with up to 49% efficiency. Light microscopy showed that a thick and robust outer nuclear layer (photoreceptors) was preserved in the treated area compared with the thin, degenerated outer nuclear layer without treatment. Substantial electroretinogram signals were detected in treated rd10 eyes, whereas control treated eyes showed minimal signals. The water maze experiment showed that the treatment substantially improved vision-guided behavior. Together, we construct and validate a translational therapeutic solution for the treatment of RP in humans. Our findings might accelerate the development of base-editing based gene therapies. Base editing technology has great potential in treating pathogenic single-nucleotide variations. Using a dual-AAV base editing system, Wu et al. restored visual functions in a mouse model of retinitis pigmentosa.

Polylactic acid (PLA) composites with multifunctional properties and minimal filler content are increasingly in demand across various industries. However, achieving a balance between high mechanical strength, electrical conductivity, thermal conductivity, and electromagnetic interference (EMI) shielding remains challenging. In this study, a dual‐processing strategy combining Pickering emulsion templating and melt blending is presented to hybridize 1D carbon nanotubes (CNTs) and 2D graphene nanoplatelets (GNPs) within a PLA matrix. This approach successfully forms a stable dual‐filler network, ensuring uniform dispersion of the fillers. The results show that this method significantly enhances the performance of the resulting PM‐PGxCy composites (P: Pickering emulsion; M: melt blending; x and y: mass fractions of GNPs and CNTs, respectively). Specifically, the PM‐PG1.43C1.43 composite exhibits remarkable improvements in mechanical strength (56.2 MPa), electrical conductivity (43.5 S m−1), EMI shielding effectiveness (20.1 dB), and thermal conductivity (0.34 W m·K−1), outperforming composites prepared using either method alone. These findings indicate that the dual‐processing strategy effectively combines 1D and 2D fillers, facilitating superior interfacial interactions and enhancing the multifunctional properties of PLA‐based composites. This study offers a new approach to achieving high‐performance PLA composites with low filler content, offering significant potential for applications in electronics, packaging, and EMI shielding technologies. Polylactic acid (PLA) composites exhibit enhanced mechanical strength, electrical and thermal conductivity, and EMI shielding through a dual‐processing strategy that combines Pickering emulsion templating and melt blending. By incorporating CNTs and GNPs into the PLA matrix, this approach results in significant multifunctional improvements, making the PM‐PG1.43C1.43 composite ideal for advanced applications.

Crops genetically engineered to produce insect-killing proteins from Bacillus thuringiensis (Bt) have revolutionized management of some major pests, but their efficacy is reduced when pests evolve resistance. Practical resistance, which is field-evolved resistance that reduces the efficacy of Bt crops and has practical implications for pest management, has been reported in 26 cases in seven countries involving 11 pest species. This special collection includes six original papers that present a global perspective on field-evolved resistance to Bt crops. One is a synthetic review providing a comprehensive global summary of the status of the resistance or susceptibility to Bt crops of 24 pest species in 12 countries. Another evaluates the inheritance and fitness costs of resistance of Diabrotica virgifera virgifera to Gpp34/Tpp35Ab (formerly called Cry34/35Ab). Two papers describe and demonstrate advances in techniques for monitoring field-evolved resistance. One uses a modified F2 screen for resistance to Cry1Ac and Cry2Ab in Helicoverpa zea in the United States. The other uses genomics to analyze nonrecessive resistance to Cry1Ac in Helicoverpa armigera in China. Two papers provide multi-year monitoring data for resistance to Bt corn in Spain and Canada, respectively. The monitoring data from Spain evaluate responses to Cry1Ab of the corn borers Sesamia nonagrioides and Ostrinia nubilalis, whereas the data from Canada track responses of O. nubilalis to Cry1Ab, Cry1Fa, Cry1A.105, and Cry2Ab. We hope the new methods, results, and conclusions reported here will spur additional research and help to enhance the sustainability of current and future transgenic insecticidal crops.

Background The burden and characteristics of respiratory viral infections in children hospitalized for acute respiratory tract infections (ARTIs) during the post-COVID-19 pandemic era are unclear. We analyzed the epidemiological and clinical characteristics of pediatric patients hospitalized with common respiratory virus infections before and after relaxation of non-pharmaceutical interventions in Hangzhou, China and evaluated the diagnostic value of the six-panel respiratory pathogen detection system. Methods Six types of respiratory viruses were detected in respiratory samples from children with suspected ARTIs by multiplex real-time quantitative polymerase chain reaction (RT-qPCR). Changes in virus detection rates and epidemiological and clinical characteristics, obtained from electronic health records, were analyzed. Binary logistic regression was used to identify respiratory tract infections risk factors. Multiplex RT-qPCR and targeted next-generation sequencing results were compared in random samples. Results Among the 11,056 pediatric samples, 3228 tested positive for one or more of six common respiratory pathogens. RSV and PIV-3 detection rates differed significantly across age groups (both P  < 0.001), and were more common in younger children. PIV-1 was more common in infants, toddlers, and preschoolers than in school-age children ( P  < 0.001). FluB was predominantly detected in school-age children ( P  < 0.001). RSV-, ADV-, and PIV-1-positivity rates were higher in 2022 than in 2023. Seasonal viral patterns differed across years. RSV (OR 9.156. 95% CI 5.905–14.195) and PIV-3 (OR 1.683, 95% CI 1.133–2.501) were risk factors for lower respiratory tract infections. RSV-positivity was associated with severe pneumonia ( P  = 0.044). PIV-3 (OR 0.391, 95% CI 0.170–0.899), summer season (OR 1.982, 95% CI 1.117–3.519), and younger age (OR 0.938, 95% CI 0.893–0.986) influenced pneumonia severity. Multiplex RT-qPCR showed good diagnostic performance. Conclusion After changes in COVID-19 prevention and control strategies, six common respiratory viruses in children were prevalent in 2022–2023, with different seasonal epidemic characteristics and age proclivities. RSV and PIV-3 cause lower, and FluA, FluB, and ADV more typically cause upper respiratory tract infections. Infancy and summer season influence severe pneumonia risk. Multiplex RT-qPCR is valuable for accurate and timely detection of respiratory viruses in children, which facilitates management, treatment, and prevention of ARTIs.