A tripartite rheostat controls self-regulated host plant resistance to insects.

Plants deploy receptor-like kinases and nucleotide-binding leucine-rich repeat receptors to confer host plant resistance (HPR) to herbivores1. These gene-for-gene interactions between insects and their hosts have been proposed for more than 50 years2. However, the molecular and cellular mechanisms that underlie HPR have been elusive, as the identity and sensing mechanisms of insect avirulence effectors have remained unknown. Here we identify an insect salivary protein perceived by a plant immune receptor. The BPH14-interacting salivary protein (BISP) from the brown planthopper (Nilaparvata lugens Stål) is secreted into rice (Oryza sativa) during feeding. In susceptible plants, BISP targets O. satvia RLCK185 (OsRLCK185; hereafter Os is used to denote O. satvia-related proteins or genes) to suppress basal defences. In resistant plants, the nucleotide-binding leucine-rich repeat receptor BPH14 directly binds BISP to activate HPR. Constitutive activation of Bph14-mediated immunity is detrimental to plant growth and productivity. The fine-tuning of Bph14-mediated HPR is achieved through direct binding of BISP and BPH14 to the selective autophagy cargo receptor OsNBR1, which delivers BISP to OsATG8 for degradation. Autophagy therefore controls BISP levels. In Bph14 plants, autophagy restores cellular homeostasis by downregulating HPR when feeding by brown planthoppers ceases. We identify an insect saliva protein sensed by a plant immune receptor and discover a three-way interaction system that offers opportunities for developing high-yield, insect-resistant crops.

Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis.

Histone acetylation plays critical roles in chromatin remodeling, DNA repair, and epigenetic regulation of gene expression, but the underlying mechanisms are unclear. Proteasomes usually catalyze ATP- and polyubiquitin-dependent proteolysis. Here, we show that the proteasomes containing the activator PA200 catalyze the polyubiquitin-independent degradation of histones. Most proteasomes in mammalian testes ("spermatoproteasomes") contain a spermatid/sperm-specific α subunit α4 s/PSMA8 and/or the catalytic ß subunits of immunoproteasomes in addition to PA200. Deletion of PA200 in mice abolishes acetylation-dependent degradation of somatic core histones during DNA double-strand breaks and delays core histone disappearance in elongated spermatids. Purified PA200 greatly promotes ATP-independent proteasomal degradation of the acetylated core histones, but not polyubiquitinated proteins. Furthermore, acetylation on histones is required for their binding to the bromodomain-like regions in PA200 and its yeast ortholog, Blm10. Thus, PA200/Blm10 specifically targets the core histones for acetylation-mediated degradation by proteasomes, providing mechanisms by which acetylation regulates histone degradation, DNA repair, and spermatogenesis.

OPEN STOMATA 1 phosphorylates CYCLIC NUCLEOTIDE-GATED CHANNELs to trigger Ca2+ signaling for abscisic acid-induced stomatal closure in Arabidopsis.

Multiple cyclic nucleotide-gated channels (CNGCs) are abscisic acid (ABA)-activated Ca2+ channels in Arabidopsis (Arabidopsis thaliana) guard cells. In particular, CNGC5, CNGC6, CNGC9, and CNGC12 are essential for ABA-specific cytosolic Ca2+ signaling and stomatal movements. However, the mechanisms underlying ABA-mediated regulation of CNGCs and Ca2+ signaling are still unknown. In this study, we identified the Ca2+-independent protein kinase OPEN STOMATA 1 (OST1) as a CNGC activator in Arabidopsis. OST1-targeted phosphorylation sites were identified in CNGC5, CNGC6, CNGC9, and CNGC12. These CNGCs were strongly inhibited by Ser-to-Ala mutations and fully activated by Ser-to-Asp mutations at the OST1-targeted sites. The overexpression of individual inactive CNGCs (iCNGCs) under the UBIQUITIN10 promoter in wild-type Arabidopsis conferred a strong dominant-negative-like ABA-insensitive stomatal closure phenotype. In contrast, expressing active CNGCs (aCNGCs) under their respective native promoters in the cngc5-1 cngc6-2 cngc9-1 cngc12-1 quadruple mutant fully restored ABA-activated cytosolic Ca2+ oscillations and Ca2+ currents in guard cells, and rescued the ABA-insensitive stomatal movement mutant phenotypes. Thus, we uncovered that ABA elicits cytosolic Ca2+ signaling via an OST1-CNGC module, in which OST1 functions as a convergence point of the Ca2+-dependent and -independent pathways in Arabidopsis guard cells.

Clinical efficacy of tumor organoid-guided cancer therapy for locally advanced unresectable or metastatic breast cancer.

Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.

Organoid forming potential as complementary parameter for accurate evaluation of breast cancer neoadjuvant therapeutic efficacy.

BACKGROUND: 13-15% of breast cancer/BC patients diagnosed as pathological complete response/pCR after neoadjuvant systemic therapy/NST suffer from recurrence. This study aims to estimate the rationality of organoid forming potential/OFP for more accurate evaluation of NST efficacy. METHODS: OFPs of post-NST residual disease/RD were checked and compared with clinical approaches to estimate the recurrence risk. The phenotypes of organoids were classified via HE staining and ER, PR, HER2, Ki67 and CD133 immuno-labeling. The active growing organoids were subjected to drug sensitivity tests. RESULTS: Of 62 post-NST BC specimens, 24 were classified as OFP-I with long-term active organoid growth, 19 as OFP-II with stable organoid growth within 3 weeks, and 19 as OFP-III without organoid formation. Residual tumors were overall correlated with OFP grades (P < 0.001), while 3 of the 18 patients (16.67%) pathologically diagnosed as tumor-free (ypT0N0M0) showed tumor derived-organoid formation. The disease-free survival/DFS of OFP-I cases was worse than other two groups (Log-rank P < 0.05). Organoids of OFP-I/-II groups well maintained the biological features of their parental tumors and were resistant to the drugs used in NST. CONCLUSIONS: The OFP would be a complementary parameter to improve the evaluation accuracy of NST efficacy of breast cancers.

Neutrophil depletion attenuates antibody-mediated rejection in a renal transplantation mouse model.

Antibody-mediated rejection (AMR) can cause graft failure following renal transplantation. Neutrophils play a key role in AMR progression, but the exact mechanism remains unclear. We investigated the effect of neutrophils on AMR in a mouse kidney transplantation model. The mice were divided into five groups: syngeneic transplantation (Syn), allograft transplantation (Allo), and three differently treated AMR groups. The AMR mouse model was established using skin grafts to pre-sensitize recipient mice. Based on the AMR model, Ly6G-specific monoclonal antibodies were administered to deplete neutrophils (NEUT-/- + AMR) and TACI-Fc was used to block B-cell-activating factor (BAFF)/a proliferation-inducing ligand (APRIL) signaling (TACI-Fc + AMR). Pathological changes were assessed using hematoxylin-eosin and immunohistochemical staining. Banff values were evaluated using the Banff 2015 criteria. Donor-specific antibody (DSA) levels were assessed using flow cytometry, and BAFF and APRIL concentrations were measured using ELISA. Compared to the Syn and Allo groups, a significantly increased number of neutrophils and increased C4d and IgG deposition were observed in AMR mice, accompanied by elevated DSA levels. Neutrophil depletion inhibited inflammatory cell infiltration and reduced C4d and IgG deposition. Neutrophil depletion significantly decreased DSA levels after transplantation and suppressed BAFF and APRIL concentrations, suggesting a mechanism for attenuating AMR-induced graft damage. Similar results were obtained after blockading BAFF/APRIL using a TACI-Fc fusion protein. In summary, neutrophil infiltration increased in the AMR mouse renal transplantation model. Neutrophil depletion or blockading the BAFF/APRIL signaling pathway significantly alleviated AMR and may provide better options for the clinical treatment of AMR.

Evaluation of TikTok videos on acute pancreatitis: content quality and reliability analysis.

BACKGROUND: Acute pancreatitis (AP) is a common acute digestive system disorder, with patients often turning to TikTok for AP-related information. However, the platform's video quality on AP has not been thoroughly investigated. OBJECTIVE: The main purpose of this study is to evaluate the quality of videos about AP on TikTok, and the secondary purpose is to study the related factors of video quality. METHODS: This study involved retrieving AP-related videos from TikTok, determining, and analyzing them based on predefined inclusion and exclusion criteria. Relevant data were extracted and compiled for evaluation. Video quality was scored using the DISCERN instrument and the Health on the Net (HONcode) score, complemented by introducing the Acute Pancreatitis Content Score (APCS). Pearson correlation analysis was used to assess the correlation between video quality scores and user engagement metrics such as likes, comments, favorites, retweets, and video duration. RESULTS: A total of 111 TikTok videos were included for analysis, and video publishers were composed of physicians (89.18%), news media organizations (13.51%), individual users (5.41%), and medical institutions (0.9%). The majority of videos focused on AP-related educational content (64.87%), followed by physicians' diagnostic and treatment records (15.32%), and personal experiences (19.81%). The mean scores for DISCERN, HONcode, and APCS were 33.05 ± 7.87, 3.09 ± 0.93, and 1.86 ± 1.30, respectively. The highest video scores were those posted by physicians (35.17 ± 7.02 for DISCERN, 3.31 ± 0.56 for HONcode, and 1.94 ± 1.34 for APCS, respectively). According to the APCS, the main contents focused on etiology (n = 55, 49.5%) and clinical presentations (n = 36, 32.4%), followed by treatment (n = 24, 21.6%), severity (n = 20, 18.0%), prevention (n = 19, 17.1%), pathophysiology (n = 17, 15.3%), definitions (n = 13, 11.7%), examinations (n = 10, 9%), and other related content. There was no correlation between the scores of the three evaluation tools and the number of followers, likes, comments, favorites, and retweets of the video. However, DISCERN (r = 0.309) and APCS (r = 0.407) showed a significant positive correlation with video duration, while HONcode showed no correlation with the duration of the video. CONCLUSIONS: The general quality of TikTok videos related to AP is poor; however, the content posted by medical professionals shows relatively higher quality, predominantly focusing on clinical presentations and etiologies. There is a discernible correlation between video duration and quality ratings, indicating that a combined approach incorporating the guideline can comprehensively evaluate AP-related content on TikTok.

GSDMA at the crossroads between pyroptosis and tumor immune evasion in glioma.

Pyroptosis, an inflammatory and programmed cell death process, has been controversial in its role in tumor immunity. However, as the first molecule in the gasdermin family, the mechanism of GSDMA in glioma growth is not well understood. We identified the differentially expressed gene GSDMA from Treg cells-related genes using the TCGA database. The biological functions of GSDMA and the relationship between GSDMA expression and tumor immune cell infiltration and cancer patient survival were investigated using open-source databases and platforms. Additionally, flow cytometry analysis was used to examine the effect of GSDMA on tumor immune cell infiltration. Our study showed that GSDMA expression played an important role in immune evasion in glioma. Patients with high GSDMA expression had a worse prognosis. In vivo studies demonstrated that GSDMA knockdown could enhance the infiltration level of CD8+ T cells. High GSDMA expression was also positively correlated with poor anti-PD-L1 treatment outcomes in GBM patients, suggesting that GSDMA may be a potential biomarker that should be considered in combination with anti-PD-L1 therapy for glioma patients. In conclusion, our study demonstrates that high GSDMA expression in gliomas is associated with immune-infiltrating cells CD8+ T cells and Treg cells, and indicates a worse prognosis in glioma. Therefore, GSDMA may serve as a therapeutic target for glioma progression and should be applied in immunotherapy for glioma patients.

Deep learning parametric response mapping from inspiratory chest CT scans: a new approach for small airway disease screening.

OBJECTIVES: Parametric response mapping (PRM) enables the evaluation of small airway disease (SAD) at the voxel level, but requires both inspiratory and expiratory chest CT scans. We hypothesize that deep learning PRM from inspiratory chest CT scans can effectively evaluate SAD in individuals with normal spirometry. METHODS: We included 537 participants with normal spirometry, a history of smoking or secondhand smoke exposure, and divided them into training, tuning, and test sets. A cascaded generative adversarial network generated expiratory CT from inspiratory CT, followed by a UNet-like network predicting PRM using real inspiratory CT and generated expiratory CT. The performance of the prediction is evaluated using SSIM, RMSE and dice coefficients. Pearson correlation evaluated the correlation between predicted and ground truth PRM. ROC curves evaluated predicted PRMfSAD (the volume percentage of functional small airway disease, fSAD) performance in stratifying SAD. RESULTS: Our method can generate expiratory CT of good quality (SSIM 0.86, RMSE 80.13 HU). The predicted PRM dice coefficients for normal lung, emphysema, and fSAD regions are 0.85, 0.63, and 0.51, respectively. The volume percentages of emphysema and fSAD showed good correlation between predicted and ground truth PRM (|r| were 0.97 and 0.64, respectively, p < 0.05). Predicted PRMfSAD showed good SAD stratification performance with ground truth PRMfSAD at thresholds of 15%, 20% and 25% (AUCs were 0.84, 0.78, and 0.84, respectively, p < 0.001). CONCLUSION: Our deep learning method generates high-quality PRM using inspiratory chest CT and effectively stratifies SAD in individuals with normal spirometry.

Elevated NT-proBNP predicts unfavorable outcomes in patients with acute ischemic stroke after thrombolytic therapy.

OBJECTIVE: Few studies correlated n-terminal pro-brain natriuretic peptide (NT-proBNP) with early neurological deterioration (END) and prognosis of acute ischaemic stroke (AIS) patients with rt-PA intravenous thrombolysis. Therefore this study aimed to investigate the relationship between NT-proBNP and END, and prognosis after intravenous thrombolysis in patients with AIS. METHODS: A total of 325 patients with AIS were enrolled. We performed the natural logarithm transformation on the NT-proBNP [ln(NT-proBNP)]. Univariate and multivariate logistic regression analyses were performed to assess the relationship between ln(NT-proBNP) and END, and prognosis and receiver operating characteristic (ROC) curves were used to show the sensitivity and specificity of NT-proBNP. RESULTS: After thrombolysis, among 325 patients with AIS, 43 patients (13.2%) developed END. In addition, three months follow-up showed a poor prognosis in 98 cases (30.2%) and a good prognosis in 227 cases (69.8%). Multivariate logistic regression analysis showed that ln(NT-proBNP) was an independent risk factor for END (OR = 1.450,95%CI:1.072 ~ 1.963, P = 0.016) and poor prognosis at three months follow-up (OR = 1.767, 95%CI: 1.347 ~ 2.317, P < 0.001) respectively. According to ROC curve analysis, ln(NT-proBNP) (AUC 0.735, 95%CI: 0.674 ~0.796, P < 0.001) had a good predictive value for poor prognosis, with a predictive value of 5.12 and sensitivity and specificity of 79.59% and 60.35% respectively. When combined with NIHSS to predict END(AUC 0.718, 95%CI: 0.631 ~ 0.805, P < 0.001) and poor prognosis(AUC 0.780, 95%CI: 0.724 ~ 0.836, P < 0.001), the predictive value of the model is further improved. CONCLUSION: NT-proBNP is independently associated with END and poor prognosis in patients with AIS following intravenous thrombolysis and has a particular predictive value for END and poor prognosis.

Large scale rice germplasm screening for identification of novel brown planthopper resistance sources.

Rice (Oryza sativa L.) is a staple food crop globally. Brown planthopper (Nilaparvata lugens Stål, BPH) is the most destructive insect that threatens rice production annually. More than 40 BPH resistance genes have been identified so far, which provide valuable gene resources for marker-assisted breeding against BPH. However, it is still urgent to evaluate rice germplasms and to explore more new wide-spectrum BPH resistance genes to combat newly occurring virulent BPH populations. To this end, 560 germplasm accessions were collected from the International Rice Research Institute (IRRI), and their resistance to current BPH population of China was examined. A total of 105 highly resistant materials were identified. Molecular screening of BPH resistance genes in these rice germplasms was conducted by developing specific functional molecular markers of eight cloned resistance genes. Twenty-three resistant germplasms were found to contain none of the 8 cloned BPH resistance genes. These accessions also exhibited a variety of resistance mechanisms as indicated by an improved insect weight gain (WG) method, suggesting the existence of new resistance genes. One new BPH resistance gene, Bph44(t), was identified in rice accession IRGC 15344 and preliminarily mapped to a 0-2 Mb region on chromosome 4. This study systematically sorted out the corresponding relationships between BPH resistance genes and germplasm resources using a functional molecular marker system. Newly explored resistant germplasms will provide valualble donors for the identification of new resistance genes and BPH resistance breeding programs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01416-x.

An L-Shaped Three-Level and Single Common Element Sparse Sensor Array for 2-D DOA Estimation.

The degree of freedom (DOF) is an important performance metric for evaluating the design of a sparse array structure. Designing novel sparse arrays with higher degrees of freedom, while ensuring that the array structure can be mathematically represented, is a crucial research direction in the field of direction of arrival (DOA) estimation. In this paper, we propose a novel L-shaped sparse sensor array by adjusting the physical placement of the sensors in the sparse array. The proposed L-shaped sparse array consists of two sets of three-level and single-element sparse arrays (TSESAs), which estimate the azimuth and elevation angles, respectively, through one-dimensional (1-D) spatial spectrum search. Each TSESA is composed of a uniform linear subarray and two sparse subarrays, with one single common element in the two sparse subarrays. Compared to existing L-shaped sparse arrays, the proposed array achieves higher degrees of freedom, up to 4Q1Q2+8Q1-5, when estimating DOA using the received signal covariance. To facilitate the correct matching of azimuth and elevation angles, the cross-covariance between the two TSESA arrays is utilized for estimation. By comparing and analyzing performance parameters with commonly used L-shaped and other sparse arrays, it is found that the proposed L-shaped TSESA has higher degrees of freedom and array aperture, leading to improved two-dimensional (2-D) DOA estimation results. Finally, simulation experiments validate the excellent performance of the L-shaped TSESA in 2-D DOA estimation.

Designing an optimization model for the vaccine supply chain during the COVID-19 pandemic.

The COVID-19 pandemic has affected people's lives worldwide. Among various strategies being applied to addressing such a global crisis, public vaccination has been arguably the most appropriate approach to control a pandemic. However, vaccine supply chain and management have become a new challenge for governments. In this study, a solution for the vaccine supply chain is presented to address the hurdles in the public vaccination program according to the concerns of the government and the organizations involved. For this purpose, a robust bi-level optimization model is proposed. At the upper level, the risk of mortality due to the untimely supply of the vaccine and the risk of inequality in the distribution of the vaccine is considered. All costs related to the vaccine supply chain are considered at the lower level, including the vaccine supply, allocation of candidate centers for vaccine injection, cost of maintenance and injection, transportation cost, and penalty cost due to the vaccine shortage. In addition, the uncertainty of demand for vaccines is considered with multiple scenarios of different demand levels. Numerical experiments are conducted based on the vaccine supply chain in Kermanshah, Iran, and the results show that the proposed model significantly reduces the risk of mortality and inequality in the distribution of vaccines as well as the total cost, which leads to managerial insights for better coordination of the vaccination network during the COVID-19 pandemic.

Necessity of rice resistance to planthoppers for OsEXO70H3 regulating SAMSL excretion and lignin deposition in cell walls.

The planthopper resistance gene Bph6 encodes a protein that interacts with OsEXO70E1. EXO70 forms a family of paralogues in rice. We hypothesized that the EXO70-dependent trafficking pathway affects the excretion of resistance-related proteins, thus impacting plant resistance to planthoppers. Here, we further explored the function of EXO70 members in rice resistance against planthoppers. We used the yeast two-hybrid and co-immunoprecipitation assays to identify proteins that play roles in Bph6-mediated planthopper resistance. The functions of the identified proteins were characterized via gene transformation, plant resistance evaluation, insect performance, cell excretion observation and cell wall component analyses. We discovered that another EXO70 member, OsEXO70H3, interacted with BPH6 and functioned in cell excretion and in Bph6-mediated planthopper resistance. We further found that OsEXO70H3 interacted with an S-adenosylmethionine synthetase-like protein (SAMSL) and increased the delivery of SAMSL outside the cells. The functional impairment of OsEXO70H3 and SAMSL reduced the lignin content and the planthopper resistance level of rice plants. Our results suggest that OsEXO70H3 may recruit SAMSL and help its excretion to the apoplast where it may be involved in lignin deposition in cell walls, thus contributing to rice resistance to planthoppers.

Charge state depletion nanoscopy with a nitrogen-vacancy center in nanodiamonds.

The development of super-resolution imaging has driven research into biological labeling, new materials' characterization, and nanoscale sensing. Here, we studied the photoinduced charge state conversion of nitrogen-vacancy (NV) centers in nanodiamonds (NDs), which show the potential for multifunction sensing and labeling at the nanoscale. Charge state depletion (CSD) nanoscopy is subsequently demonstrated for the diffraction-unlimited imaging of NDs in biological cells. A resolution of 77 nm is obtained with 50 nm NDs. The depletion laser power of CSD nanoscopy is approximately 1/16 of stimulated emission depletion (STED) microscopy with the same resolution. The results can be used to improve the spatial resolution of biological labeling and sensing with NDs and other nanoparticles.

Rapid determination and dietary intake risk assessment of 249 pesticide residues in Panax notoginseng.

UPLC-MS/MS and GC-MS/MS were used to establish a method to simultaneously determine various pesticide residues in Panax notoginseng. Results showed that the limits of detection of 249 pesticides were all 5-10 µg/kg. The detection rate of pesticides in 121 P. notoginseng samples was 93.39%, and 19 pesticides were detected. According to the US Code of Federal Regulations, the Chinese Pharmacopoeia recommended algorithm, and the Japanese "positive list system", the pass rates of pesticide residues were 100%, 99.17%, and 89.26%, respectively. The chronic risk quotient (ADI%) and acute risk quotient (ARfD%) of P. notoginseng were 0.00-0.12% and 0.00-0.15%, respectively. In summary, the detection method established in this study can be used for routine analysis of various P. notoginseng pesticide residues. The pesticide residues in the main root samples of P. notoginseng were at a safe level and unlikely pose health risks to consumers.

Transcriptome and Metabolome Profiling Reveal the Resistance Mechanisms of Rice against Brown Planthopper.

Brown planthopper (Nilaparvata lugens Stål, BPH) is one of the most destructive insects affecting rice production. To better understand the physiological mechanisms of how rice responds to BPH feeding, we analyzed BPH-induced transcriptomic and metabolic changes in leaf sheaths of both BPH-susceptible and -resistant rice varieties. Our results demonstrated that the resistant rice reduced the settling, feeding and growth of BPH. Metabolic analyses indicated that BPH infestation caused more drastic overall metabolic changes in the susceptible variety than the resistant rice. Differently accumulated metabolites (DAMs) belonging to flavonoids were downregulated in the susceptible rice but upregulated in resistant variety. Transcriptomic analyses revealed more differentially expressed genes (DEGs) in susceptible rice than resistant rice, and DEGs related to stimulus were significantly upregulated in resistant rice but downregulated in susceptible rice. Combined analyses of transcriptome and metabolome showed that many DEGs and DAMs were enriched in phenylpropane biosynthesis, flavonoid biosynthesis, and plant hormone signal transduction. We conducted correlation analyses of DEGs and DAMs in these pathways and found a high correlation between DEGs and DAMs. Then, we found that the contents of endogenous indole 3-acetic acid (IAA) in resistant rice was lower than that of susceptible rice after BPH feeding, while the salicylic acid (SA) content was the opposite. For functional analysis, an exogenous application of IAA decreased rice resistance to BPH, but the exogenous application of SA increased resistance. In addition, biochemical assessment and quantitative PCR analysis showed that the lignin content of resistant accession was constitutively higher than in susceptible accession. By adding epigallocatechin, the substrate of anthocyanidin reductase (ANR), to the artificial diet decreased the performance of BPH. We first combined a transcriptome-metabolome-wide association study (TMWAS) on rice resistance to BPH in this study. We demonstrated that rice promoted resistance to BPH by inducing epigallocatechin and decreasing IAA. These findings provided useful transcriptomic and metabolic information for understanding the rice-BPH interactions.

Positive Periodic Solution for Second-Order Nonlinear Differential Equations with Variable Coefficients and Mixed Delays.

In this paper, we study two types of second-order nonlinear differential equations with variable coefficients and mixed delays. Based on Krasnoselskii's fixed point theorem, the existence results of positive periodic solution are established. It should be pointed out that the equations we studied are more general. Therefore, the results of this paper have better applicability.

Integrating GIS in reorganizing blood supply network in a robust-stochastic approach by combating disruption damages.

As supplying adequate blood in multiple countries has failed due to the Covid-19 pandemic, the importance of redesigning a sensible protective-resilience blood supply chain is underscored. The outbreak-as an extensive disruption-has caused a delay in ordering and delivering blood and its by-products, which leads to severe social and financial loss to healthcare organizations. This paper presents a robust multi-phase optimization approach to model a blood supply network ensuring blood is collected efficiently. We evaluate the effectiveness of the model using real-world data from two mechanisms. Firstly, a Geographic Information System (GIS)-based method is presented to find potential alternative locations for blood donation centers to maximize availability, accessibility, and proximity to blood donors. Then, a protective mathematical model is developed with the incorporation of (a) blood perishability, (b) efficient collation centers, (c) multiple-source of suppliers, (d) back-up centers, (e) capacity limitation, and (f) uncertain demand. Emergency back-up for laboratory centers to supplement and offset the processing plants against the possible disorders is applied in a two-stage stochastic robust optimization model to maximize the level of hospitals' coverage. The results highlight the fraction cost of considering back-up facilities in the total costs and provide more resilient decisions with lower risks by examining resource limitations.

Molecular and functional analysis of a brown planthopper resistance protein with two nucleotide-binding site domains.

The brown planthopper (Nilaparvata lugens Stål, BPH) resistance gene BPH9 encodes an unusual coiled-coil (CC) nucleotide-binding leucine-rich repeat (LRR) protein with two nucleotide-binding site (NBS) domains. To understand how this CC-NBS-NBS-LRR (CNNL) protein regulates defense signaling and BPH resistance, we dissected each domain's functions. The CC domain of BPH9 self-associated and was sufficient to induce cell death. The region of 97-115 residues in the CC domain is crucial for self-association and activation. NBS2, which contains a complete set of NBS function motifs and inhibits CC domain activation, rather than NBS1, acts as a molecular switch to regulate the activity of BPH9. We demonstrated that the CC domain, the NBS domain, and the LRR domain of BPH9 associate with each other and themselves in planta. Further domain swapping experiments revealed that the CC domains of BPH9 and susceptible alleles were similarly competent to induce resistance and the hypersensitive response, while the LRR domain of BPH9 confers resistance specificity to BPH. These findings provide new insights into the regulatory mechanisms governing the activity of CNNL proteins.