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Anlotinib has strong antiangiogenic effects and leads to vessel normalization. However, the "window period" characteristic in regulating vessel normalization by anlotinib cannot fully explain the long-term survival benefits achieved through combining it with other drugs. In this study, through RNA sequencing (RNA-seq) and label-free quantitative proteomics analysis, we discovered that anlotinib regulated the expression of components of the extracellular matrix (ECM), leading to a significant reduction in ECM stiffness. Our bioinformatic analysis revealed a potential positive relationship between the ECM pathway and gefitinib resistance, poor treatment outcomes for programmed death 1 (PD-1) targeting, and unfavourable prognosis following chemotherapy in lung cancer patients. We administered anlotinib in combination with these antitumour drugs and visualized their distribution using fluorescent labelling in various tumour types. Notably, our results demonstrated that anlotinib prolonged the retention time and distribution of antitumour drugs at the tumour site. Moreover, the combination therapy induced notable loosening of the tumour tissue structure. This reduction was associated with decreased interstitial fluid pressure and tumour solid pressure. Additionally, we observed that anlotinib effectively suppressed the Ras homologue family member A (RhoA)/Rho-associated protein kinase (ROCK) signalling pathway. These findings suggest that, in addition to its antiangiogenic and vessel normalization effects, anlotinib can increase the distribution and retention of antitumour drugs in tumours by modulating ECM expression and physical properties through the RhoA/ROCK signalling pathway. These valuable insights contribute to the development of combination therapies aimed at improving tumour targeting in cancer treatment.

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Recently, hydrogel sensors have been widely applied in wearable and portable electronics, but the low mechanical property, intolerance of fatigue, and low sensitivity and adhesion limit their further applications. In this study, sulfonated nanocellulose (SCNF) with dual functionality was blended into polyacrylamide (PAM) hydrogel matrix to reinforce the mechanical strength and facilitate the homogeneous dispersion of carbon nanotubes (CNTs). The SCNF-CNT/PAM hydrogel was designed through free radical polymerization to achieve commendable mechanical, electrical, and multifunctional properties. The environmental-friendly SCNF serves as bio-templates to facilitate the assembling of CNT into integrated SCNF-CNT structures with good dispersity, thus enabling the establishment of an integrated conducting and reinforcing network. The fabricated SCNF-CNT/PAM hydrogel exhibited outstanding compressive strength (∼0.45 MPa at 50 % strain), tensile strength (∼169.12 kPa), and antifatigue capacity under cyclic stretching and pressing. Furthermore, the multifunctional sensors assembled using this hydrogel demonstrated high strain sensitivity (gauge factor ~ 3.7 at 100-400 % strain) and effectively detected human motions. This design principle provides promising prospects for constructing next-generation multifunctional flexible sensors, and the integration of these distinctive properties enables the prepared composite hydrogels to find potential applications in various areas, such as implantable soft electronic devices, electronic skin, and human movement monitoring.

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PURPOSE: Nonalcoholic steatohepatitis (NASH) has been an increasingly significant contributor to hepatocellular carcinoma (HCC). Understanding the progression from NASH to HCC is critical to early diagnosis and elucidating the underlying mechanisms. RESULTS: 5 significant prognostic genes related to NASH-HCC transformation were identified through algorithm selection, which were ME1, TP53I3, SOCS2, GADD45G and CYP7A1. A diagnostic model for NASH prediction was established (AUC=0.988). TP53I3 and SOCS2 were selected as potential critical genes in the progression of NASH-HCC by external dataset validation and in vitro experiments on NASH and HCC cell lines. Immune infiltration analysis illustrated the correlation between 5 significant prognostic genes and immune cells. Single-cell analysis identified hepatocytes related to NASH-HCC transformation markers, revealing their promoting role in the transformation from NASH to HCC. CONCLUSION: With bulk-seq analysis and single-cell analysis, 5 significant prognostic genes related to NASH-HCC transformation were identified and validated at both dataset and in vitro experiment level. Among them, TP53I3 and SOCS2 might be potential critical genes in NASH-HCC progression. Single-cell analysis identified and revealed the critical role that NASH-HCC related hepatocytes play in NASH-HCC tansformation. Our research may introduce a new perspective to the diagnosis, treatment of NASH-related HCC.

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BACKGROUND: Phosphorus (P) deficiency, a major nutrient stress, greatly hinders plant growth. Phosphate (Pi) uptake in plant roots relies on PHT1 family transporters. However, melon (Cucumis melo L.) lacks comprehensive identification and characterization of PHT1 genes, particularly their response patterns under diverse stresses. RESULTS: This study identified and analyzed seven putative CmPHT1 genes on chromosomes 3, 4, 5, 6, and 7 using the melon genome. Phylogenetic analysis revealed shared motifs, domain compositions, and evolutionary relationships among genes with close histories. Exon number varied from 1 to 3. Collinearity analysis suggested segmental and tandem duplications as the primary mechanisms for CmPHT1 gene family expansion. CmPHT1;4 and CmPHT1;5 emerged as a tandemly duplicated pair. Analysis of cis-elements in CmPHT1 promoters identified 14 functional categories, including putative PHR1-binding sites (P1BS) in CmPHT1;4, CmPHT1;6, and CmPHT1;7. We identified that three WRKY transcription factors regulated CmPHT1;5 expression by binding to its W-box element. Notably, CmPHT1 promoters harbored cis-elements responsive to hormones and abiotic factors. Different stresses regulated CmPHT1 expression differently, suggesting that the adjusted expression patterns might contribute to plant adaptation. CONCLUSIONS: This study unveils the characteristics, evolutionary diversity, and stress responsiveness of CmPHT1 genes in melon. These findings lay the foundation for in-depth investigations into their functional mechanisms in Cucurbitaceae crops.

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As a contribution to expand accessibility in the territory of bio-based nanomaterials, we demonstrate a novel material strategy to convert amorphous xylan preserved in wood biomass to hierarchical assemblies of crystalline nanoxylan on a multi-length scale. By reducing the end group in pressurized hot water extracted (PHWE) xylan to primary alcohol as a xylitol form with borohydride reduction, the endwise-peeling depolymerization is effectively impeded in the alkali-catalyzed hydrolytic cleavage of side substitutions in xylan. Nanoprecipitation by a gradual pH decrease resulted in a stable hydrocolloid dispersion in the form of worm-like nanoclusters assembled with primary crystallites, owing to the self-assembly of debranched xylan driven by strong intra- and inter-chain H-bonds. With evaporation-induced self-assembly, we can further construct the hydrocolloids as dry submicron spheroids of crystalline nanoxylan (CNX) with a high average elastic modulus of 47-83 GPa. Taking the advantage that the chain length and homogeneity of PHWE-xylan can be tailored, a structure-performance correlation was established between the structural order in CNX and the phosphorescent emission of this crystalline biopolymer. Rigid clusterization and high crystallinity that are constructed by strong intra- and inter-molecule interactions within the nanoxylan effectively restrict the molecular motion, thereby promoting the emission of ultralong organic phosphorescence.

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Global climate change exerts a significant impact on sustainable horticultural crop production and quality. Rising Global temperatures have compelled the agricultural community to adjust planting and harvesting schedules, often necessitating earlier crop cultivation. Notably, climate change introduces a suite of ominous factors, such as greenhouse gas emissions (CGHs), including elevated temperature, increased carbon dioxide (CO2) concentrations, nitrous oxide (N2O) and methane (CH4) ozone depletion (O3), and deforestation, all of which intensify environmental stresses on crops. Consequently, climate change stands poised to adversely affect crop yields and livestock production. Therefore, the primary objective of the review article is to furnish a comprehensive overview of the multifaceted factors influencing horticulture production, encompassing fruits, vegetables, and plantation crops with a particular emphasis on greenhouse gas emissions and environmental stressors such as high temperature, drought, salinity, and emission of CO2. Additionally, this review will explore the implementation of novel horticultural crop varieties and greenhouse technology that can contribute to mitigating the adverse impact of climate change on agricultural crops.

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Breast cancer poses a significant risk to women worldwide, yet specific role of SERPINA gene family in breast cancer remains unclarified. Data were collected from online databases. SERPINA family gene expression was presented, and prognosis value was evaluated. Multi-omics methods were employed to explore the SERPINA-related biological processes, followed by comprehensive analyses of their roles in breast cancer. Single-cell data were analyzed to characterize the SERPINA family gene expression in different cell clusters. We selected SERPINA5 as the target gene. Via pan-cancer analysis, SERPINA5 was also investigated in various cancers. The experimental validation was conducted in MDA-MB-231 cell line eventually. SERPINA family showed differential expression in breast cancer, which were mainly expressed in myeloid cells, epithelial cells, and dendritic cells. SERPINA5 expression was upregulated in breast cancer, which was associated with a better prognosis. Immune infiltration illustrated the positive correlativity between SERPINA5 intensity and eosinophilic recruitment. Pan-cancer analysis indicated the function of SERPINA5 as a potential biomarker in other cancers. Finally, experimental validation demonstrated that SERPINA5 contributes to lower invasion and metastatic potential of breast cancer cells. With bioinformatics analysis, the significant role SERPINA family genes functioned in breast cancer was comprehensively explored, with SERPINA5 emerging as a key gene in suppressing breast cancer progression.

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The analysis of longitudinal data from electronic health records (EHRs) has the potential to improve clinical diagnoses and enable personalized medicine, motivating efforts to identify disease subtypes from patient comorbidity information. Here we introduce an age-dependent topic modeling (ATM) method that provides a low-rank representation of longitudinal records of hundreds of distinct diseases in large EHR datasets. We applied ATM to 282,957 UK Biobank samples, identifying 52 diseases with heterogeneous comorbidity profiles; analyses of 211,908 All of Us samples produced concordant results. We defined subtypes of the 52 heterogeneous diseases based on their comorbidity profiles and compared genetic risk across disease subtypes using polygenic risk scores (PRSs), identifying 18 disease subtypes whose PRS differed significantly from other subtypes of the same disease. We further identified specific genetic variants with subtype-dependent effects on disease risk. In conclusion, ATM identifies disease subtypes with differential genome-wide and locus-specific genetic risk profiles.

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Congo red is hard to remove from dye wastewater due to its structure stability and high chemical oxygen demand. In this study, cationic cellulose nanofibrils (CCNF) prepared from herb residues was physically crosslinked with sodium alginate (SA) in the presence of calcium ions, and the obtained CCNF/SA beads were used to adsorb Congo red. Results showed that CCNF/SA beads with porous internal structure were beneficial to adsorption. The maximum adsorption capacity of Congo red could reach to 518.4 mg/g, which was superior to most cellulose-based adsorption materials. Furthermore, the equilibrium adsorption isotherms and XPS analysis indicated the adsorption for Congo red was a physical process, and hydrogen bond and electrostatic adsorption were proposed as dominant adsorption mechanism. In addition, the Congo red removal efficiency of the beads was still higher than 70% after three cycles. Therefore, this high efficiency and green beads have great potential as adsorbents for anionic dyes removal.

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BACKGROUND/AIMS: This study aims to evaluate the clinical efficacy of botulinum toxin type A (BTXA) injection and augmented-dosed surgery in the treatment of acute acquired concomitant esotropia (AACE), and explore potential risk factors associated with recurrence. METHODS: A total of 104 patients diagnosed with AACE between October 2020 and January 2021 were included and voluntarily chose to undergo augmented surgery or BTXA injection. The follow-up assessments ended in November 2022. Multivariable linear regression analysis was used to identify potential factors that influence the dose-response of bilateral medial rectus recession (MRrec). Kaplan-Meier survival analyses and Cox proportional hazards models were performed to evaluate rate and risk factors for AACE relapse. RESULTS: A total of 31 AACE patients chose augmented-dosed esotropia surgery, and 73 chose BTXA treatment. During the 2-year follow-up, the surgical group achieved more stable postoperative results with no recurrence of diplopia, while only 68.68% (95% CI 55.31% to 78.79%) patients achieved orthophoria in the BTXA group. For patients undergoing BTXA treatment, hours of near work per day were demonstrated to be a significant risk factor for AACE relapse (HR 1.29, 95% CI 1.00 to 1.67). The dose-response of augmented-dosed bilateral MRrec was positively correlated with preoperative deviation angle (R2=0.833; ß=0.043, 95% CI 0.031 to 0.055; p<0.001). CONCLUSION: Our findings provided quantitative evidence that augmented-dosed surgery would achieve more stable and favourable surgical outcomes for AACE patients compared with BTXA injection. However, BTXA treatment is still proposed for patients with small deviation angles due to its advantages of reduced trauma, operational simplicity, low cost and quick recovery.

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Many diseases show patterns of co-occurrence, possibly driven by systemic dysregulation of underlying processes affecting multiple traits. We have developed a method (treeLFA) for identifying such multimorbidities from routine health-care data, which combines topic modeling with an informative prior derived from medical ontology. We apply treeLFA to UK Biobank data and identify a variety of topics representing multimorbidity clusters, including a healthy topic. We find that loci identified using topic weights as traits in a genome-wide association study (GWAS) analysis, which we validated with a range of approaches, only partially overlap with loci from GWASs on constituent single diseases. We also show that treeLFA improves upon existing methods like latent Dirichlet allocation in various ways. Overall, our findings indicate that topic models can characterize multimorbidity patterns and that genetic analysis of these patterns can provide insight into the etiology of complex traits that cannot be determined from the analysis of constituent traits alone.

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Carbon emission is a central factor in the study of the greenhouse effect and a crucial consideration in environmental policy making. Therefore, it is essential to establish carbon emission prediction models to provide scientific guidance for leaders in implementing effective carbon reduction policies. However, existing research lacks comprehensive roadmaps that integrate both time series prediction and analysis of influencing factors. This study combines the environmental Kuznets curve (EKC) theory to classify and qualitatively analyzes research subjects based on national development patterns and levels. Considering the autocorrelated characteristics of carbon emissions and their correlation with other influencing factors, we propose an integrated carbon emission prediction model named SSA-FAGM-SVR. This model optimizes the fractional accumulation grey model (FAGM) and support vector regression (SVR) using the sparrow search algorithm (SSA), considering both time series and influencing factors. The model is subsequently applied to predict the carbon emissions of the G20 for the next 10 years. The results demonstrate that this model significantly improves prediction accuracy compared to other mainstream prediction algorithms, exhibiting strong adaptability and high accuracy.

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Nanocellulose (NC) isolated from natural cellulose resources, which mainly includes cellulose nanofibril (CNF) and cellulose nanocrystal (CNC), has garnered increased attention in recent decades due to its outstanding physical and chemical properties. Various chemical modifications have been developed with the aim of surface-modifying NC for highly sophisticated applications. This review comprehensively summarizes the chemical modifications applied to NC so far in order to introduce new functionalities to the material, such as silanization, esterification, oxidation, etherification, grafting, coating, and others. The new functionalities obtained through such surface-modification methods include hydrophobicity, conductivity, antibacterial properties, and absorbability. In addition, the incorporation of NC in some functional materials, such as films, wearable sensors, cellulose nanospheres, aerogel, hydrogels, and nanocomposites, is discussed in relation to the tailoring of the functionality of NC. It should be pointed out that some issues need to be addressed during the preparation of NC and NC-based materials, such as the low reactivity of these raw materials, the difficulties involved in their scale-up, and their high energy and water consumption. Over the past decades, some methods have been developed, such as the use of pretreatment methods, the adaptation of low-cost starting raw materials, and the use of environmentally friendly chemicals, which support the practical application of NC and NC-based materials. Overall, it is believed that as a green, sustainable, and renewable nanomaterial, NC is will be suitable for large-scale applications in the future.

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In order to develop multifunctional quaternary ammonium salts and explore their advantages as modifiers for wastewater treatment, castor oil-based quaternary ammonium salts were synthesised and subsequently used as modifiers for attapulgite treatment. The structures of untreated and treated attapulgite were compared by Fourier transform infrared spectra and X-ray diffraction. The mechanism of modification was speculated. Various factors such as the amount of modified attapulgite, temperature and pH were also investigated in the batch experiments on the removal rates of acetone and phenol from wastewaters. The synthesis conditions were set as follows: the reaction temperature was 80 °C, the reaction time was 8 h, the molar ratio of castor oil to N,N-dimethyl-1,3-propanediamine was 1:5, the catalyst was 6% NaOH and the product yield was about 64.72%. The grafting rate of the castor oil-based quaternary ammonium salt was about 99.6% when the amount of modifier was 0.69 g per 5 g of attapulgite, the ultrasound treatment time was 11 min and the pH was 5. The quaternary ammonium salt was only associated with the surface of attapulgite and did not change the rod-like crystal structure of the silicate. The modified attapulgite is much more fibrous and exhibits a good distribution of crystal bundles. The removal rates were found to be less favourable under strongly acidic and strongly alkaline conditions. Under suitable conditions, for 50 mL industrial wastewaters (phenol: 100-160 mg/L; acetone: 680-800 mg/L), the amount of modified attapulgite was 1 g, the temperature was 80 °C and the pH was 7, and the maximum removal rates of acetone and phenol after 80 min reached about 65.71% and 78.72%, respectively, which were higher than those of ATP.

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Nanotechnology has achieved great attention due to its impressive performance especially engineered nanoparticles (ENPs). Copper-based nanoparticles offer favorable development in the fabrication of agrochemicals including fertilizers and pesticides in the field of agriculture. However, their toxic impact on melon plants (Cucumis melo) still needs to be investigated. Therefore, the aim of the current work was performed to focus on the toxic impact of Cu oxide nanoparticles (CuONPs) in hydroponically grown Cucumis melo. Our results demonstrated that CuONPs with 75, 150, and 225 mg/L significantly (P<0.005) suppressed the growth rate and badly affect physiological and biochemical activities in melon seedlings. Also, results revealed remarkable phenotypical changes besides significantly reduced fresh biomass and decreased levels of total chlorophyll contents in a dose-dependent manner. Atomic absorption spectroscopy (ASS) analysis exhibited that C. melo treated with CuONPs accumulates NPs in the shoot. Moreover, exposure to higher CuONPs (75-225mg/L) significantly increased the reactive oxygen species (ROS) accumulation, malondialdehyde (MDA), and hydrogen peroxide (H2O2) level in the shoot and induced toxicity in melon root with an increase in electrolyte leakage. Furthermore, antioxidant enzyme peroxidase (POD) and superoxide dismutase (SOD) activity in the shoot significantly increased under exposure to higher CuONPs. Exposure to higher concentrations of CuONPs (225 mg/L) significantly deformed the stomatal aperture. Furthermore, reducing the number and abnormal size of palisade mesophyll and spongy mesophyll cells were investigated especially at high doses of CuONPs. Overall, our current work demonstrates that CuONPs of 10-40 nm size provide direct evidence for a toxic effect in C. melo seedlings. Our findings were expected to inspire the safe production of NPs and agrifood security. Thus, CuONPs prepared from toxic route and its bioaccumulation into our food chain through crop plants possess a serious threat to the ecological system.

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InAs/GaAs quantum dot (QD) laser monolithically grown on silicon is one of the potential approaches to realizing silicon-based light sources. However, the mismatch between GaAs and Si generates a high density of threading dislocations (TDs) and antiphase boundaries (APBs), which trap carriers and adversely affect device performance. In this paper, we present a simple method to reduce the threading dislocation density (TDD) merely through GaAs buffer, eliminating the intricate dislocation filter layers (DFLs) as well as any intermediate buffer layers whose compositions are different from the target GaAs. An APB-free epitaxial 2.5 µm GaAs film was grown on exact Si (001) by metalorganic chemical vapor deposition (MOCVD) with a TDD of 9.4 × 106 cm-2. InAs/GaAs QDs with a density of 5.2 × 1010 cm-2 were grown on this GaAs/Si (001) virtual substrate by molecular beam epitaxy (MBE) system. The fabricated QD laser has achieved a single facet room temperature continuous-wave output power of 138 mW with a threshold current density of 397 A/cm2 and a lasing wavelength of 1306 nm. In this work, we propose a simplified method to fabricate high-power QD lasers, which is expected to promote the application of photonic integrated circuits.

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Recently, a solar-driven evaporator has been applied in seawater desalination, but the low stability, high cost, and complex fabrication limit its further application. Herein, we report a novel, low-cost, scalable, and easily fabricated pulp-natural rubber (PNR) foam with a unique porous structure, which was directly used as a solar-driven evaporator after facile surface carbonization. This surface carbonized PNR (CPNR) foam without interface adhesion or modification was composed of a top photothermal layer with light absorption ability and a bottom hydrophilic foam layer with a porous and interconnected network structure. Due to the strong light absorption ability (93.2%) of the carbonized top layer, together with the low thermal conductivity (0.1 W m K-1) and good water adsorption performance (9.9 g g-1) of the bottom layer, the evaporation rate and evaporation efficiency of the pulp foam evaporator under 1 sun of illumination attained 1.62 kg m-2 h-1 and 98.09%, respectively, which were much higher than those of most cellulose-based solar-driven evaporators. Furthermore, the CPNR foam evaporator with high cost-effectiveness presented high light-thermal conversion, heat localization, and good salt rejection properties due to the unique porous structure. Additionally, the CPNR foam evaporator exhibited potential applications in the treatments of simulated sewage, metal ion concentration, and seawater desalination. Its cost-effectiveness was clearly higher than that of most reported evaporators as well. Therefore, this novel, low-cost, and stable pulp foam evaporator demonstrated here can be a very promising solution for water desalination and purification.

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We aim to explore the association between caffeine and its metabolites and bone mineral density (BMD) in postmenopausal women. Data of 4286 postmenopausal women were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2009-14 in this cross-sectional study. Weighted linear regression and stepwise regression analyses were used to screen the covariates. Weighted univariate and multivariate linear regression analyses were used to explore the associations between caffeine and its metabolites and BMD. The evaluation index was estimated value (ß) with 95 % confidence intervals (CIs). We also explored these relationships in age subgroups. The median BMD level among the eligible women was 0⋅7 gm/cm2. After adjusting for covariates including age, body mass index (BMI), fat intake, Calcium (Ca) supplements, diabetes mellitus (DM), angina pectoris, parental history of osteoporosis (OP), anti-osteoporosis therapy, poverty income ratio (PIR), vitamin D (VD) supplements, coronary heart disease (CHD), and previous fracture, we found that caffeine intake was not significantly related to the BMD reduction (ß = 0, P = 0⋅135). However, caffeine metabolites, including MethyluricAcid3, MethyluricAcid7, MethyluricAcid37, Methylxanthine3, and Methylxanthine37, were negatively associated with the BMD (all P < 0⋅05). In addition, MethyluricAcid37 and Methylxanthine37 were negatively associated with BMD in females aged <65 years old, while MethyluricAcid3 and Methylxanthine3 were noteworthy in those who aged ≥65 years old. The roles of caffeine and its metabolites in BMD reduction and OP in postmenopausal women needed further exploration.

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In this paper, the design of low probability of intercept (LPI) radar waveforms considers not only the performance of passive interception systems (PISs), but also radar detection and resolution performance. Waveform design is an important considerations for the LPI ability of radar. Since information theory has a powerful performance-bound description ability from the perspective of information flow, LPI waveforms are designed in this paper within the constraints of the detection performance metrics of radar and PISs, both of which are measured by the Kullback-Leibler divergence, and the resolution performance metric, which is measured by joint entropy. The designed optimization model of LPI waveforms can be solved using the sequential quadratic programming (SQP) method. Simulation results verify that the designed LPI waveforms not only have satisfactory target-detecting and resolution performance, but also have a superior low interception performance against PISs.