A balance between vector survival and virus transmission is achieved through JAK/STAT signaling inhibition by a plant virus.

Viruses pose a great threat to animal and plant health worldwide, with many being dependent on insect vectors for transmission between hosts. While the virus-host arms race has been well established, how viruses and insect vectors adapt to each other remains poorly understood. Begomoviruses comprise the largest genus of plant-infecting DNA viruses and are exclusively transmitted by the whitefly Bemisia tabaci. Here, we show that the vector Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway plays an important role in mediating the adaptation between the begomovirus tomato yellow leaf curl virus (TYLCV) and whiteflies. We found that the JAK/STAT pathway in B. tabaci functions as an antiviral mechanism against TYLCV infection in whiteflies as evidenced by the increase in viral DNA and coat protein (CP) levels after inhibiting JAK/STAT signaling. Two STAT-activated effector genes, BtCD109-2 and BtCD109-3, mediate this anti-TYLCV activity. To counteract this vector immunity, TYLCV has evolved strategies that impair the whitefly JAK/STAT pathway. Infection of TYLCV is associated with a reduction of JAK/STAT pathway activity in whiteflies. Moreover, TYLCV CP binds to STAT and blocks its nuclear translocation, thus, abrogating the STAT-dependent transactivation of target genes. We further show that inhibition of the whitefly JAK/STAT pathway facilitates TYLCV transmission but reduces whitefly survival and fecundity, indicating that this JAK/STAT-dependent TYLCV-whitefly interaction plays an important role in keeping a balance between whitefly fitness and TYLCV transmission. This study reveals a mechanism of plant virus-insect vector coadaptation in relation to vector survival and virus transmission.

The essential role of clathrin-mediated endocytosis and early endosomes in the trafficking of begomoviruses through the primary salivary glands of their whitefly vectors.

IMPORTANCE: Many plant viruses are transmitted by insect vectors in a circulative manner. For efficient transmission, the entry of the virus from vector hemolymph into the primary salivary gland (PSG) is a step of paramount importance. Yet, vector components mediating virus entry into PSG remain barely characterized. Here, we demonstrate the role of clathrin-mediated endocytosis and early endosomes in begomovirus entry into whitefly PSG. Our findings unravel the key components involved in begomovirus transport within the whitefly body and transmission by their whitefly vectors and provide novel clues for blocking begomovirus transmission.

CLCuMuV subverts the processing of hydroxyproline-rich systemin to suppress tobacco defenses against insect vectors.

The interactions of insect vector-virus-plant have important ecological and evolutionary implications. The constant struggle of plants against viruses and insect vectors has driven the evolution of multiple defense strategies in the host as well as counter-defense strategies in the viruses and insect vectors. Cotton leaf curl Multan virus (CLCuMuV) is a major causal agent of cotton leaf curl disease in Asia and is exclusively transmitted by the whitefly Bemisia tabaci. Here, we report that plants infected with CLCuMuV and its betasatellite, cotton leaf curl Multan betasatellite (CLCuMuB) enhance the performance of B. tabaci vector, and ßC1 encoded by CLCuMuB plays an important role in begomovirus-whitefly-tobacco tripartite interactions. We showed that CLCuMuB ßC1 suppresses the jasmonic acid signaling pathway by interacting with the subtilisin-like protease 1.7 (NtSBT1.7) protein, thereby enhancing whitefly performance on tobacco plants. Further studies revealed that in the wild type plants, NtSBT1.7 could process tobacco preprohydroxyproline-rich systemin B (NtpreproHypSysB). After CLCuMuB infection, CLCuMuB ßC1 could interfere with the processing of NtpreproHypSysB by NtSBT1.7, thereby impairing plant defenses against whitefly. These results contribute to our understanding of the tripartite interactions among virus, plant, and whitefly, thus offering ecological insights into the spread of vector insect populations and the prevalence of viral diseases.

Deep insights into the biofilm formation mechanism and nitrogen-transformation network in a nitrate-dependent anaerobic methane oxidation biofilm.

Nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) process offers a promising solution for simultaneously achieving methane emissions reduction and efficient nitrogen removal in wastewater treatment. Although nitrogen removal at a practical rate has been achieved by n-DAMO biofilm process, the mechanisms of biofilm formation and nitrogen transformation remain to be elucidated. In this study, n-DAMO biofilms were successfully developed in the membrane aerated moving bed biofilm reactor (MAMBBR) and removed nitrate at a rate of 159 mg NO3--N L-1 d-1. The obvious increase in the content of extracellular polymeric substances (EPS) indicated that EPS production was important for biofilm development. n-DAMO microorganisms dominated the microbial community, and n-DAMO bacteria were the most abundant microorganisms. However, the expression of biosynthesis genes for proteins and polysaccharides encoded by n-DAMO archaea was significantly more active compared to other microorganisms, suggesting the central role of n-DAMO archaea in EPS production and biofilm formation. In addition to nitrate reduction, n-DAMO archaea were revealed to actively express dissimilatory nitrate reduction to ammonium and nitrogen fixation. The produced ammonium was putatively converted to dinitrogen gas through the joint function of n-DAMO archaea and n-DAMO bacteria. This study revealed the biofilm formation mechanism and nitrogen-transformation network in n-DAMO biofilm systems, shedding new light on promoting the application of n-DAMO process.

Bipolar Molecular Torque Wrench Modulates the Stacking of Two-Dimensional Metal-Organic Framework Nanosheets.

The precise modulation of nanosheet stacking modes introduces unforeseen properties and creates momentous applications but remains a challenge. Herein, we proposed a strategy using bipolar molecules as torque wrenches to control the stacking modes of 2-D Zr-1,3,5-(4-carboxylphenyl)-benzene metal-organic framework (2-D Zr-BTB MOF) nanosheets. The bipolar phenyl-alkanes, phenylmethane (P-C1) and phenyl ethane (P-C2), predominantly instigated the rotational stacking of Zr-BTB-P-C1 and Zr-BTB-P-C2, displaying a wide angular distribution. This included Zr-BTB-P-C1 orientations at 0, 12, 18, and 24° and Zr-BTB-P-C2 orientations at 0, 6, 12, 15, 24, and 30°. With reduced polarity, phenyl propane (P-C3) and phenyl pentane (P-C5) introduced steric hindrance and facilitated alkyl hydrophobic interactions with the nanosheets, primarily resulting in the modulation of eclipsed stacking for Zr-BTB-P-C3 (64.8%) and Zr-BTB-P-C5 (93.3%) nanosheets. The precise angle distributions of four Zr-BTB-P species were in agreement with theoretical calculations. The alkyl induction mechanism was confirmed by the sequential guest replacement and 2-D 13C-1H heteronuclear correlation (HETCOR). In addition, at the single-particle level, we first observed that rotational stacked pores exhibited similar desorption rates for xylene isomers, while eclipsed stacked pores showed significant discrepancy for xylenes. Moreover, the eclipsed nanosheets as stationary phases exhibited high resolution, selectivity, repeatability, and durability for isomer separation. The universality was proven by another series of bipolar acetate-alkanes. This bipolar molecular torque wrench strategy provides an opportunity to precisely control the stacking modes of porous nanosheets.

Association of caesarean delivery with offspring health outcomes in full-cohort versus sibling-comparison studies: a comparative meta-analysis and simulation study.

BACKGROUND: Full-cohort and sibling-comparison designs have yielded inconsistent results about the impacts of caesarean delivery on offspring health outcomes, with the effect estimates from the latter being more likely directed towards the null value. We hypothesized that the seemingly conservative results obtained from the sibling-comparison design might be attributed to inadequate adjustment for non-shared confounders between siblings, particularly maternal age at delivery. METHODS: A systematic review and meta-analysis was first conducted. PubMed, Embase, and the Web of Science were searched from database inception to April 6, 2022. Included studies (1) examined the association of caesarean delivery, whether elective or emergency, with offspring health outcomes; (2) simultaneously conducted full-cohort and sibling-comparison analyses; and (3) reported adjusted effect estimates with 95% confidence intervals (95% CIs). No language restrictions were applied. Data were extracted by 2 reviewers independently. Three-level meta-analytic models were used to calculate the pooled odds ratios (ORs) and 95% CIs for caesarean versus vaginal delivery on multiple offspring health outcomes separately for full-cohort and sibling-comparison designs. Subgroup analyses were performed based on the method of adjustment for maternal age at delivery. A simulation study was then conducted. The simulated datasets were generated with some key parameters derived from the meta-analysis. RESULTS: Eighteen studies involving 21,854,828 individuals were included. The outcomes assessed included mental and behavioral disorders; endocrine, nutritional and metabolic diseases; asthma; cardiorespiratory fitness; and multiple sclerosis. The overall pooled OR for estimates from the full-cohort design was 1.14 (95% CI: 1.11 to 1.17), higher than that for estimates from the sibling-comparison design (OR = 1.08; 95% CI: 1.02 to 1.14). Stratified analyses showed that estimates from the sibling-comparison design varied considerably across studies using different methods to adjust for maternal age at delivery in multivariate analyses, while those from the full-cohort design were rather stable: in studies that did not adjust maternal age at delivery, the pooled OR of full-cohort vs. sibling-comparison design was 1.10 (95% CI: 0.99 to 1.22) vs. 1.06 (95% CI: 0.85 to 1.31), in studies adjusting it as a categorical variable, 1.15 (95% CI: 1.11 to 1.19) vs. 1.07 (95% CI: 1.00 to 1.15), and in studies adjusting it as a continuous variable, 1.12 (95% CI: 1.05 to 1.19) vs. 1.12 (95% CI: 0.98 to 1.29). The severe underestimation bias related to the inadequate adjustment of maternal age at delivery in sibling-comparison analyses was fully replicated in the simulation study. CONCLUSIONS: Sibling-comparison analyses may underestimate the association of caesarean delivery with multiple offspring health outcomes due to inadequate adjustment of non-shared confounders, such as maternal age at delivery. Thus, we should be cautious when interpreting the seemingly conservative results of sibling-comparison analyses in delivery-related studies.

Experimental 61-partite entanglement on a three-dimensional photonic chip.

Multipartite entanglements are essential resources for proceeding tasks in quantum information science and technology. However, generating and verifying them present significant challenges, such as the stringent requirements for manipulations and the need for a huge number of building-blocks as the systems scale up. Here, we propose and experimentally demonstrate the heralded multipartite entanglements on a three-dimensional photonic chip. Integrated photonics provide a physically scalable way to achieve an extensive and adjustable architecture. Through sophisticated Hamiltonian engineering, we are able to control the coherent evolution of shared single photon in the multiple spatial modes, dynamically tuning the induced high-order W-states of different orders in a single photonic chip. Using an effective witness, we successfully observe and verify 61-partite quantum entanglements in a 121-site photonic lattice. Our results, together with the single-site-addressable platform, offer new insights into the accessible size of quantum entanglements and may facilitate the developments of large-scale quantum information processing applications.

Experimental Boson Sampling Enabling Cryptographic One-Way Function.

Boson sampling is a computational problem, which is commonly believed to be a representative paradigm for attaining the milestone of quantum advantage. So far, massive efforts have been made to the experimental large-scale boson sampling for demonstrating this milestone, while further applications of the machines remain a largely unexplored area. Here, we investigate experimentally the efficiency and security of a cryptographic one-way function that relies on coarse-grained boson sampling, in the framework of a photonic boson-sampling machine fabricated by a femtosecond laser direct writing technique. Our findings demonstrate that the implementation of the function requires moderate sample sizes, which can be over 4 orders of magnitude smaller than the ones predicted by the Chernoff bound; whereas for numbers of photons n≥3 and bins d∼poly(m,n), the same output of the function cannot be generated by nonboson samplers. Our Letter is the first experimental study that deals with the potential applications of boson sampling in the field of cryptography and paves the way toward additional studies in this direction.

Evidence for Nitrous Oxide Emissions by Nitrite-Dependent Anaerobic Methane Oxidizing Bacteria.

Nitrite-dependent anaerobic methane oxidizing (n-DAMO) bacteria generally convert nitrite to dinitrogen and bypass the nitrous oxide (N2O) formation step. However, N2O is often detected in n-DAMO bacteria dominated cultures and it remains an open question as to the microbial origin of N2O in these enrichments. Using a stable nitrite consuming microbial community enriched for n-DAMO bacteria, we demonstrated that N2O production was coupled to methane oxidation and the higher initial nitrite concentrations led to increased quantities of N2O being formed. Moreover, continuous exposure of the enrichment culture to about 5 mg of N L-1 nitrite resulted in constant N2O being produced (12.5% of nitrite was reduced to N2O). Metatranscriptomic analyses revealed that nitrite reductase (nirS) and nitric oxide reductase (norZ) transcripts from n-DAMO bacteria increased in response to nitrite exposure. No other bacteria significantly expressed nor genes under these conditions, suggesting n-DAMO bacteria are responsible for N2O being produced. In a 35-day bioreactor experiment, N2O produced by the n-DAMO bacteria accumulated when nitrite was in excess; this was found to be up to 3.2% of the nitrogen that resulted from nitrite removal. Together, these results suggested that excess nitrite is an important driver of N2O production by n-DAMO bacteria. To this end, proper monitoring and control of nitrite levels in wastewater treatment plants would be effective strategies for mitigating N2O emissions to the atmosphere.

A plant DNA virus replicates in the salivary glands of its insect vector via recruitment of host DNA synthesis machinery.

Whereas most of the arthropod-borne animal viruses replicate in their vectors, this is less common for plant viruses. So far, only some plant RNA viruses have been demonstrated to replicate in insect vectors and plant hosts. How plant viruses evolved to replicate in the animal kingdom remains largely unknown. Geminiviruses comprise a large family of plant-infecting, single-stranded DNA viruses that cause serious crop losses worldwide. Here, we report evidence and insight into the replication of the geminivirus tomato yellow leaf curl virus (TYLCV) in the whitefly (Bemisia tabaci) vector and that replication is mainly in the salivary glands. We found that TYLCV induces DNA synthesis machinery, proliferating cell nuclear antigen (PCNA) and DNA polymerase δ (Polδ), to establish a replication-competent environment in whiteflies. TYLCV replication-associated protein (Rep) interacts with whitefly PCNA, which recruits DNA Polδ for virus replication. In contrast, another geminivirus, papaya leaf curl China virus (PaLCuCNV), does not replicate in the whitefly vector. PaLCuCNV does not induce DNA-synthesis machinery, and the Rep does not interact with whitefly PCNA. Our findings reveal important mechanisms by which a plant DNA virus replicates across the kingdom barrier in an insect and may help to explain the global spread of this devastating pathogen.

The transcriptional regulator JAZ8 interacts with the C2 protein from geminiviruses and limits the geminiviral infection in Arabidopsis.

Jasmonates (JAs) are phytohormones that finely regulate critical biological processes, including plant development and defense. JASMONATE ZIM-DOMAIN (JAZ) proteins are crucial transcriptional regulators that keep JA-responsive genes in a repressed state. In the presence of JA-Ile, JAZ repressors are ubiquitinated and targeted for degradation by the ubiquitin/proteasome system, allowing the activation of downstream transcription factors and, consequently, the induction of JA-responsive genes. A growing body of evidence has shown that JA signaling is crucial in defending against plant viruses and their insect vectors. Here, we describe the interaction of C2 proteins from two tomato-infecting geminiviruses from the genus Begomovirus, tomato yellow leaf curl virus (TYLCV) and tomato yellow curl Sardinia virus (TYLCSaV), with the transcriptional repressor JAZ8 from Arabidopsis thaliana and its closest orthologue in tomato, SlJAZ9. Both JAZ and C2 proteins colocalize in the nucleus, forming discrete nuclear speckles. Overexpression of JAZ8 did not lead to altered responses to TYLCV infection in Arabidopsis; however, knock-down of JAZ8 favors geminiviral infection. Low levels of JAZ8 likely affect the viral infection specifically, since JAZ8-silenced plants neither display obvious developmental phenotypes nor present differences in their interaction with the viral insect vector. In summary, our results show that the geminivirus-encoded C2 interacts with JAZ8 in the nucleus, and suggest that this plant protein exerts an anti-geminiviral effect.

Chemical Topology and Complexity of Protein Architectures.

Chemical topology has emerged as one intriguing feature in protein engineering. Nature demonstrates the elegance and power of protein topology engineering in the unique biofunctions and exceptional stabilities of cyclotides and lasso peptides. With entangling protein motifs and genetically encoded peptide-protein chemistry, artificial proteins with complex topologies, including cyclic proteins, star proteins, and protein catenanes, have become accessible. Among them, proteins with mechanical bonds ('mechanoproteins') are of special interest, owing to their potential functional benefits such as structure stabilization, quaternary structure control, synergistic multivalency effect, and dynamic mechanical sliding/switching properties. In this review article, we summarize recent progress in the field of protein topology engineering as well as the challenges and opportunities that it holds.

A vector whitefly endocytic receptor facilitates the entry of begomoviruses into its midgut cells via binding to virion capsid proteins.

Many circulative plant viruses transmitted by insect vectors are devastating to agriculture worldwide. The midgut wall of vector insects represents a major barrier and at the same time the key gate a circulative plant virus must cross for productive transmission. However, how these viruses enter insect midgut cells remains poorly understood. Here, we identified an endocytic receptor complex for begomoviruses in the midgut cells of their whitefly vector. Our results show that two whitefly proteins, BtCUBN and BtAMN, compose a receptor complex BtCubam, for which BtCUBN contributes a viral-binding region and BtAMN contributes to membrane anchorage. Begomoviruses appear to be internalized together with BtCubam via its interaction with the 12-19 CUB domains of BtCUBN via clathrin-dependent endocytosis. Functional analysis indicates that interruption of BtCUBN and BtAMN lead to reduction of virus acquisition and transmission by whitefly. In contrast, CUBN-begomovirus interaction was not observed in two non-competent whitefly-begomovirus combinations. These observations suggest a major role of the specific endocytic receptor in facilitating viral entry into vector midgut cells.

Armet from whitefly saliva acts as an effector to suppress plant defences by targeting tobacco cystatin.

Arginine rich, mutated in early stage of tumours (Armet), is a well-characterized bifunctional protein as an unfolded protein response component intracellularly and a neurotrophic factor extracellularly in mammals. Recently, a new role of Armet as an effector protein mediating insect-plant interactions has been reported; however, its molecular mechanisms underlying the regulation of plant defences remain unclear. We investigated the molecular mechanisms underlying whitefly-secreted Armet-mediated regulation of insect-plant interaction by agrobacterium-mediated transient expression, RNA interference, electrical penetration graph, protein-protein interaction studies, virus-induced gene silencing assay, phytohormone analysis and whitefly bioassays. Armet, secreted by Bemisia tabaci whitefly, is highly expressed in the primary salivary gland and is delivered into tobacco plants during feeding. Overexpression of the BtArmet gene in tobacco enhanced whitefly performance, while silencing the BtArmet gene in whitefly interrupted whitefly feeding and suppressed whitefly performance on tobacco plants. BtArmet was shown to interact with NtCYS6, a cystatin protein essential for tobacco anti-whitefly resistance, and counteract the negative effects of NtCYS6 on whitefly. These results indicate that BtArmet is a salivary effector and acts to promote whitefly performance on tobacco plants through binding to the tobacco cystatin NtCYS6. Our findings provide novel insight into whitefly-plant interactions.

Reducing circuit complexity in optical quantum computation using 3D architectures.

Integrated photonic architectures based on optical waveguides are one of the leading candidates for the future realisation of large-scale quantum computation. One of the central challenges in realising this goal is simultaneously minimising loss whilst maximising interferometric visibility within waveguide circuits. One approach is to reduce circuit complexity and depth. A major constraint in most planar waveguide systems is that beamsplitter transformations between distant optical modes require numerous intermediate SWAP operations to couple them into nearest neighbour proximity, each of which introduces loss and scattering. Here, we propose a 3D architecture which can significantly mitigate this problem by geometrically bypassing trivial intermediate operations. We demonstrate the viability of this concept by considering a worst-case 2D scenario, where we interfere the two most distant optical modes in a planar structure. Using femtosecond laser direct-writing technology we experimentally construct a 2D architecture to implement Hong-Ou-Mandel interference between its most distant modes, and a 3D one with corresponding physical dimensions, demonstrating significant improvement in both fidelity and efficiency in the latter case. In addition to improving fidelity and efficiency of individual non-adjacent beamsplitter operations, this approach provides an avenue for reducing the optical depth of circuits comprising complex arrays of beamsplitter operations.

Direct Observation of Dynamically Localized Quantum Optical States.

Quantum-correlated biphoton states play an important role in quantum communication and processing, especially considering the recent advances in integrated photonics. However, it remains a challenge to flexibly transport quantum states on a chip, when dealing with large-scale sophisticated photonic designs. The equivalence between certain aspects of quantum optics and solid-state physics makes it possible to utilize a range of powerful approaches in photonics, including topologically protected boundary states, graphene edge states, and dynamic localization. Optical dynamic localization allows efficient protection of classical signals in photonic systems by implementing an analogue of an external alternating electric field. Here, we report on the observation of dynamic localization for quantum-correlated biphotons, including both the generation and the propagation aspects. As a platform, we use sinusoidal waveguide arrays with cubic nonlinearity. We record biphoton coincidence count rates as evidence of robust generation of biphotons and demonstrate the dynamic localization features in both spatial and temporal space by analyzing the quantum correlation of biphotons at the output of the waveguide array. Experimental results demonstrate that various dynamic modulation parameters are effective in protecting quantum states without introducing complex topologies. Our Letter opens new avenues for studying complex physical processes using photonic chips and provides an alternative mechanism of protecting communication channels and nonclassical quantum sources in large-scale integrated quantum optics.

Deciphering the Inhibition of Ethane on Anaerobic Ammonium Oxidation.

Anaerobic ammonium oxidation (anammox) and nitrification, two common biological ammonium oxidation pathways, are critical for the microbial nitrogen cycle. Short chain alkanes (C2-C8) have been well-known as inhibitors for nitrification through interaction with the ammonia monooxygenase, while whether these alkanes affect anammox is an open question. Here, this work demonstrated significant inhibition of ethane on anammox and revealed the inhibitory mechanism. The acute inhibition of ethane on anammox was concentration-dependent and reversible; 0.86 mM dissolved ethane caused 50% inhibition (IC50), and 1.72 mM ethane almost completely inhibited anammox. After long-term exposure to 0.09 mM ethane for 30 days, the ammonium (nitrite) removal rate dropped from 202 (267) mg N L-1 d-1 to 1 (1) mg N L-1 d-1, and the abundance of anammox bacteria decreased from 61.9% to 9.5%. The intercellular ammonium concentration of anammox bacteria decreased after ethane exposure, while metatranscriptome analysis showed significant upregulation of genes for ammonium transport of anammox bacteria. Thus, ethane could suppress ammonium uptake resulting in the inhibition of anammox activities. As ethane is the second most prevalent alkane after methane in various anoxic environments, ethane may have an important effect on the nitrogen cycle driven by anammox that should be investigated in future research.

Research progress in targeted therapies for gastric cancer.

Patients with advanced gastric cancer experience rapid disease progression with limited survival, high mortality, and a lack of surgical options. Thus, radiochemotherapy or a combination of chemotherapeutics with targeted therapy is the mainstay of treatment. In comparison to the treatment of other malignant tumors, in gastric cancer, the development of molecularly targeted drugs has been relatively slow. Currently, there are two major classes of molecularly targeted drug regimens that have achieved a certain efficacy in clinical practice: anti-vascular endothelial growth factor (anti-VEGF) therapy and anti-epidermal growth factor receptor (anti-EGFR) therapy. Trastuzumab has been approved as the standard of care for first-line treatment in advanced human epidermal growth factor receptor 2 (HER2)-positive gastric cancer. Ramucirumab in combination with paclitaxel is the recommended regimen for second-line treatment, and apatinib is recommended as third-line treatment. This review summarizes the current status of targeted therapies in the treatment of gastric cancer and gives a perspective on the future.

Novel mutation signatures in the prognosis of EGFR-TKIs targeted therapy for non-small cell lung cancer patients based on the 1000-gene panel sequencing.

The application of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) may be affected by somatic mutations. The purpose of this study was to explore the effect of mutations on the prognosis and tumor markers of NSCLC patients treated with EGFR-TKIs. 21 NSCLC patients treated with EGFR-TKIs were selected, and the targeted sequencing of the tumor tissues or whole blood samples with the 1000-gene panel was conducted to screen mutations. Afterward, functional enrichment analysis was performed based on mutant genes. Subsequently, the correlation between mutations and clinical indicators, prognosis, and tumor markers were analyzed. Finally, the prognosis after taking osimertinib was compared between NSCLC patients with EGFR p.T790M positive and negative mutations, and the EGFR p.T790M concomitant and uncommon mutations were screened. A total of 485 mutations in 251 genes were identified, in which MTOR, AXIN2, AR, EGFR, NOTCH1, and HRAS mutations were significantly correlated with PFS and/or tumor markers. There was no significant difference in PFS, therapeutic effect, and prognosis between EGFR p.T790M positive and negative patients who received osimertinib treatment. Besides, we also found 80 concomitant mutations and 54 uncommon mutations of EGFR p.T790M. AR, HRAS, EGFR, AXIN2, NOTCH1, and MTOR might be key genes to the prognosis of NSCLC treated with EGFR-TKIs. Osimertinib has certain efficacy in EGFR p.T790M negative NSCLC patients.

A salivary effector enables whitefly to feed on host plants by eliciting salicylic acid-signaling pathway.

Phloem-feeding insects feed on plant phloem using their stylets. While ingesting phloem sap, these insects secrete saliva to circumvent plant defenses. Previous studies have shown that, to facilitate their feeding, many phloem-feeding insects can elicit the salicylic acid- (SA-) signaling pathway and thus suppress effective jasmonic acid defenses. However, the molecular basis for the regulation of the plant's defense by phloem-feeding insects remains largely unknown. Here, we show that Bt56, a whitefly-secreted low molecular weight salivary protein, is highly expressed in the whitefly primary salivary gland and is delivered into host plants during feeding. Overexpression of the Bt56 gene in planta promotes susceptibility of tobacco to the whitefly and elicits the SA-signaling pathway. In contrast, silencing the whitefly Bt56 gene significantly decreases whitefly performance on host plants and interrupts whitefly phloem feeding with whiteflies losing the ability to activate the SA pathway. Protein-protein interaction assays show that the Bt56 protein directly interacts with a tobacco KNOTTED 1-like homeobox transcription factor that decreases whitefly performance and suppresses whitefly-induced SA accumulation. The Bt56 orthologous genes are highly conserved but differentially expressed in different species of whiteflies. In conclusion, Bt56 is a key salivary effector that promotes whitefly performance by eliciting salicylic acid-signaling pathway.