ß-Ga2O3 Air-Channel Field-Emission Nanodiode with Ultrahigh Current Density and Low Turn-On Voltage.

Field-emission nanodiodes with air-gap channels based on single ß-Ga2O3 nanowires have been investigated in this work. With a gap of ∼50 nm and an asymmetric device structure, the proposed nanodiode achieves good diode characteristics through field emission in air at room temperature. Measurement results show that the nanodiode exhibits an ultrahigh emission current density, a high enhancement factor of >2300, and a low turn-on voltage of 0.46 V. More impressively, the emission current almost keeps constant over a wide range (8 orders of magnitude) of air pressures below 1 atm. Meanwhile, the fluctuation in field-emission current is below 8.7% during long-time monitoring, which is better than the best reported field-emission device based on ß-Ga2O3 nanostructures. All of these results indicate that ß-Ga2O3 air-gapped nanodiodes are promising candidates for vacuum electronics that can also operate in air.

Spatio-Temporal Study of Galactolipid Biosynthesis in Duckweed Using Mass Spectrometry Imaging and in vivo Isotope Labeling.

Isotope labeling coupled with mass spectrometry imaging (MSI) presents a potent strategy for elucidating the dynamics of metabolism at cellular resolution, yet its application to plant systems is scarce. It has the potential to reveal the spatio-temporal dynamics of lipid biosynthesis during plant development. In this study, we explore its application to galactolipid biosynthesis of an aquatic plant, Lemna minor, with D2O labeling. Specifically, matrix-assisted laser desorption/ionization-MSI data of two major galactolipids in L. minor, monogalactosyldiacylglycerol and digalactosyldiacylglycerol, were studied after growing in 50% D2O media over a 15-day time period. When they were partially labeled after 5 d, three distinct binomial isotopologue distributions were observed corresponding to the labeling of partial structural moieties: galactose only, galactose and a fatty acyl chain and the entire molecule. The temporal change in the relative abundance of these distributions follows the expected linear pathway of galactolipid biosynthesis. Notably, their mass spectrometry images revealed the localization of each isotopologue group to the old parent frond, the intermediate tissues and the newly grown daughter fronds. Besides, two additional labeling experiments, (i) 13CO2 labeling and (ii) backward labeling of completely 50% D2O-labeled L. minor in H2O media, confirm the observations in forward labeling. Furthermore, these experiments unveiled hidden isotopologue distributions indicative of membrane lipid restructuring. This study suggests the potential of isotope labeling using MSI to provide spatio-temporal details in lipid biosynthesis in plant development.

Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study.

Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers. Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers. Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023. Exposure: Pregnancy after breast cancer. Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes. Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival. Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03673306.

Predicting Fingerprint Age Based on Ozonolysis Kinetics of Unsaturated Triacylglycerol Degradation.

Answering the question, "How old is a fingerprint?", is a highly sought-after aim in forensic science. Despite several decades of studies to find an empirical correlation in fingerprint aging, there has been no reliable method so far. In this study, we attempt to determine the time since deposition (TSD) of aged fingerprints from the chemical profile captured within a matrix-assisted laser desorption/ionization mass spectrometry data set. Our approach is based on the chemical kinetics associated with the ambient ozonolysis of unsaturated triacylglycerols (TGs), a major component in fingerprint lipids. First, ozone concentration and ambient temperature were determined to be the major factors in the degradation of unsaturated TGs. A simple kinetics model is then developed to describe the decay of unsaturated TGs, dictated only by the temperature and ozone concentration. This model is then applied to the degradation of TGs in a mixture of TG standards and multiple individuals' fingerprints. The overall decay of unsaturated TGs follows the pseudo-first-order reaction kinetics, validating our hypothesis; however, there are significant person-to-person variations in the initial abundance of unsaturated TGs and the decay rate, hampering the accurate prediction of TSD unless they are corrected for each individual. Nevertheless, the model's applicability for ambient fingerprint aging data was successfully demonstrated.

Disrupted intestinal mucosal barrier mediated by alcohol consumption aggravates systemic microplastic accumulation.

Waste plastics are degraded into microplastics (MPs), which are easily accumulated in the human body through digestive tracts, via the food chain. Alcohol is a widely consumed chemical throughout the world with the ability to alter the intestinal barrier. For this reason, this study was aimed to investigate exact relevance between alcohol consumption and organ distributions of MPs in an ethanol feeding animal model characterized by disrupted intestinal mucosal barriers. In this study, C57BL/6 mice were separated into control, control + MP, ethanol (EtOH), and EtOH + MP groups. Mice in the EtOH group ingested a Lieber-DeCarli diet containing EtOH. Mice in the MP groups ingested 0.1 mg/kg fluorophore polymerized polystyrene microplastics via oral gavage polystyrene MPs via oral gavage. The EtOH + MP group showed higher MP accumulation in the liver than the control + MP group. The same pattern was observed in the intestines, spleen, and brain. This pattern was more prominent in the intestines, with the EtOH + MP group showing the most severe damage due to EtOH ingestion. This result suggests that the intestinal mucosa disruption caused by EtOH ingestion exacerbates MP accumulation in the organs. Moreover, hepatic steatosis was more severe in the EtOH + MP group than in the EtOH group, suggesting the secondary manifestation mediated by MP accumulation. This study reports a novel MP accumulation pattern in the body by providing novel insights into alcohol-induced gut permeability and microplastics toxicity from the perspective of gut-liver axis.

Apocrine cystomatosis: From the aspect of epithelial-mesenchymal transition.

Apocrine cystomatosis, also called epitrichial sweat gland cystomatosis, is a non-neoplastic condition characterised by multiple dilated cysts of sweat gland origin. Histopathologically, these cysts comprise two layers of cells: an inner layer of glandular epithelial cells and an outer layer of myoepithelial cells. A case of apocrine cystomatosis was admitted to a local hospital. The microscopic investigation revealed that some enlarged cysts showed the transition of glandular epithelial cells into a spindle, mesenchymal cell-like morphology. The epithelial-to-mesenchymal transition (EMT) has long been studied as a pathway for embryogenesis, organ development, and carcinogenesis. While various molecular factors, including cytokines and growth factors, are known to induce EMT, mechanical forces have also been proposed to initiate EMT. The present case describes a possible relationship between EMT occurring in a cystic condition and further pathological inspection.

Measurement of the NOx reduction effect on food wastewater during waste incineration.

Incineration is the most effective method for reducing the increasing waste volume. However, as the pollutants generated during incineration may cause secondary pollution, blocking them in advance is necessary. During incineration, prevention facilities are operated to reduce the amount of pollutants. Conventional selective non-catalytic reduction (SNCR) reduces nitrogen oxides (NOx) by injecting ammonia and urea as reducing agents. In this study, the NOx reduction effect on food wastewater (FW) was examined. In addition, the removal efficiency was compared at different concentrations of urea mixed with FW. When different concentrations of urea were injected in SNCR facilities A, B and C, NOx removal efficiencies of up to 75% were observed; with FW injection only, removal efficiency was 56%; and when both urea and FW were injected, removal efficiency was up to 79%. Although FW showed a lower NOx removal efficiency than urea, injecting both increased the efficiency. In addition, when air pollutant emissions and the incinerator temperature were analysed, we found that they could be managed without exceeding the allowed limits. However, for the injection and incineration of reducing agents, the characteristics of the incineration facility and reducing agents must be considered.

Efficient Hydrogen-Deuterium Exchange in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging for Confident Metabolite Identification.

Highly efficient hydrogen-deuterium exchange (HDX) is developed for mass spectrometry imaging (MSI) with low-vacuum matrix-assisted laser desorption/ionization (MALDI). A HDX efficiency of 73-85% is achieved by introducing D2O vapor into a heated MALDI source in combination with a deuterium-labeled matrix, which allows correct determination of the number of possible H/D exchanges for up to 17 labile hydrogens. This provides valuable orthogonal information to supplement m/z, allowing for increased confidence in metabolite identification while retaining the spatial information MSI supplies. When combined with high-throughput METASPACE annotation, this approach can systematically improve untargeted metabolite annotations in MALDI-MS imaging. The developed method was applied to MALDI-MS imaging of the top surface, bottom surface, and middle section of Lemna minor fronds. Out of a total of 56 on-sample annotations made with the BraChem database using a 10% false discovery rate, 31 of these annotations (55%) matched our HDX data, providing additional confidence. For the remaining 45%, our data allowed us to narrow down structural possibilities and eliminate incorrect structures, greatly increasing confidence in metabolite identification.

Rapid and Automatic Annotation of Multiple On-Tissue Chemical Modifications in Mass Spectrometry Imaging with Metaspace.

On-tissue chemical derivatization is a valuable tool for expanding compound coverage in untargeted metabolomic studies with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Applying multiple derivatization agents in parallel increases metabolite coverage even further but results in large and more complex datasets that can be challenging to analyze. In this work, we present a pipeline to provide rigorous annotations for on-tissue derivatized MSI data using Metaspace. To test and validate the pipeline, maize roots were used as a model system to obtain MSI datasets after chemical derivatization with four different reagents, Girard's T and P for carbonyl groups, coniferyl aldehyde for primary amines, and 2-picolylamine for carboxylic acids. Using this pipeline helped us annotate 631 unique metabolites from the CornCyc/BraChem database compared to 256 in the underivatized dataset, yet, at the same time, shortening the processing time compared to manual processing and providing robust and systematic scoring and annotation. We have also developed a method to remove false derivatized annotations, which can clean 5-25% of false derivatized annotations from the derivatized data, depending on the reagent. Taken together, our pipeline facilitates the use of broadly targeted spatial metabolomics using multiple derivatization reagents.

Effect of Colloidal Interactions and Hydrodynamic Stress on Particle Deposition in a Single Micropore.

Clogging is ubiquitous. It happens in a wide range of material processing and causes severe performance degradation or process breakdown. In this study, we investigate clogging dynamics in a single micropore by controlling the surface property of the particle and processing condition. Microfluidic observation is conducted to investigate particle deposition in a contraction microchannel where polystyrene suspension is injected as a feed solution. The particle deposition area is quantified using the images taken using a CCD camera in both upstream and downstream of the microchannel. Pressure drop across the microchannel is also measured. When the particle interaction is repulsive, the deposition occurs mostly in downstream, while an opposite tendency is identified when the particle interaction is attractive. More complex deposition characteristics are found as the flow rate is changed. Particle flux density and the ratio of lift force to colloidal force are introduced to explain the clogging dynamics. This study provides a useful insight to alleviate clogging issues by controlling the colloidal interaction and hydrodynamic stress.

Knowledge, attitudes, and perceptions associated with HPV vaccination among female Korean and Chinese university students.

BACKGROUND: Human papillomavirus (HPV) vaccination is a form of primary prevention for cervical cancer. The HPV vaccination rate of female university students is not high in Korea and China. Therefore, the purpose of this study was to identify and compare the factors associated with intention to receive HPV vaccination between Korean and Chinese female university students. METHODS: The participants were 273 Korean and 317 Chinese female university students who had not been vaccinated for HPV, and data were collected using a self-reported questionnaire about attitudes toward HPV vaccination, HPV knowledge, perceptions of HPV infection, and intention to receive HPV vaccine. RESULTS: There were no significant differences between the Korean and Chinese female university students in HPV knowledge, attitudes, perceptions, and vaccination intention. The factors influencing the intention of HPV vaccination in Korean students were a positive attitude toward the HPV vaccine and a high HPV knowledge score. For Chinese students, sexual experience, awareness of genital warts, a positive attitude toward the HPV vaccine, a high HPV knowledge scores, a perception of the seriousness of HPV infection, and negative emotions regarding HPV infection were significant factors. CONCLUSIONS: It is important to improve attitudes and knowledge about HPV and the HPV vaccine in order to enhance HPV vaccination both in Korea and China. Perceived seriousness and negative emotions regarding HPV infection should be used as a framework to develop subject-tailored interventions in China.

Evaluation of Toxicity and Efficacy of Inotodiol as an Anti-Inflammatory Agent Using Animal Model.

Chaga mushroom (Inonotus obliquus) comprises polyphenolic compounds, triterpenoids, polysaccharides, and sterols. Among the triterpenoid components, inotodiol has been broadly examined because of its various biological activities. The purpose of this study is to examine inotodiol from a safety point of view and to present the potential possibilities of inotodiol for medical usage. From chaga mushroom extract, crude inotodiol (INO20) and pure inotodiol (INO95) were produced. Mice were treated with either INO20 or INO95 once daily using oral administration for repeated dose toxicity evaluation. Serum biochemistry parameters were analyzed, and the level of pro-inflammatory cytokines in the serum was quantified. In parallel, the effect of inotodiol on food allergic symptoms was investigated. Repeated administration of inotodiol did not show any mortality or abnormalities in organs. In food allergy studies, the symptoms of diarrhea were ameliorated by administration with INO95 and INO20. Furthermore, the level of MCPT-1 decreased by treatment with inotodiol. In this study, we demonstrated for the first time that inotodiol does not cause any detrimental effect by showing anti-allergic activities in vivo by inhibiting mast cell function. Our data highlight the potential to use inotodiol as an immune modulator for diseases related to inflammation.

Policy responses to COVID-19 and stock market reactions - An international evidence.

The COVID-19 pandemic has caused escalating levels of business, economic and societal uncertainty and created extensive disruptions around the world. Policymakers have responded with a variety of measures to combat this unprecedented crisis. This paper investigates the stock market reactions to the national policy responses. We focus on the two influential policy actions: the nationwide lockdown order aiming to slow down the spread of the Coronavirus, and the interest rate cut policy aiming to minimize the negative economic impact of the pandemic. The Difference-In-Difference method is employed to conduct a cross-country analysis. We find that both policy actions have a significant and positive impact on the stock market performance. We also document a larger stock market reaction to the announcement of an interest rate cut policy than that of a lockdown order.

Single-Cell Metabolomics by Mass Spectrometry Imaging.

Multicellular organisms achieve their complex living activities through the highly organized metabolic interplay of individual cells and tissues. This complexity has driven the need to spatially resolve metabolomics down to the cellular and subcellular level. Recent technological advances have enabled mass spectrometry imaging (MSI), especially matrix-assisted laser desorption/ionization (MALDI), to become a powerful tool for the visualization of molecular species down to subcellular spatial resolution. In the present chapter, we summarize recent advances in the field of MALDI-MSI, with respect to single-cell level resolution metabolomics directly on tissue. In more detail, we focus on advancements in instrumentation for MSI at single-cell resolution, and the applications towards metabolomic scale imaging. Finally, we discuss new computational tools to aid in metabolite identification, future perspective, and the overall direction that the field of single-cell metabolomics directly on tissue may take in the years to come.

Transcriptional regulatory control of mammalian nephron progenitors revealed by multi-factor cistromic analysis and genetic studies.

Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. However, little is known about the regulatory intersection of these players. Here, we have mapped nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and Wt1. We identified 373 multi-factor associated 'regulatory hotspots' around genes closely associated with progenitor programs. To examine their functional significance, we deleted 'hotspot' enhancer elements for Six2 and Wnt4. Removal of the distal enhancer for Six2 leads to a ~40% reduction in Six2 expression. When combined with a Six2 null allele, progeny display a premature depletion of nephron progenitors. Loss of the Wnt4 enhancer led to a significant reduction of Wnt4 expression in renal vesicles and a mildly hypoplastic kidney, a phenotype also enhanced in combination with a Wnt4 null mutation. To explore the regulatory landscape that supports proper target gene expression, we performed CTCF ChIP-seq to identify insulator-boundary regions. One such putative boundary lies between the Six2 and Six3 loci. Evidence for the functional significance of this boundary was obtained by deep sequencing of the radiation-induced Brachyrrhine (Br) mutant allele. We identified an inversion of the Six2/Six3 locus around the CTCF-bound boundary, removing Six2 from its distal enhancer regulation, but placed next to Six3 enhancer elements which support ectopic Six2 expression in the lens where Six3 is normally expressed. Six3 is now predicted to fall under control of the Six2 distal enhancer. Consistent with this view, we observed ectopic Six3 in nephron progenitors. 4C-seq supports the model for Six2 distal enhancer interactions in wild-type and Br/+ mouse kidneys. Together, these data expand our view of the regulatory genome and regulatory landscape underpinning mammalian nephrogenesis.

A 3D Printable Electroconductive Biocomposite Bioink Based on Silk Fibroin-Conjugated Graphene Oxide.

Reduced graphene oxide (rGO) has wide application as a nanofiller in the fabrication of electroconductive biocomposites due to its exceptional properties. However, the hydrophobicity and chemical stability of rGO limit its ability to be incorporated into precursor polymers for physical mixing during biocomposite fabrication. Moreover, until now, no suitable rGO-combining biomaterials that are stable, soluble, biocompatible, and 3D printable have been developed. In this study, we fabricated digital light processing (DLP) printable bioink (SGOB1), through covalent reduction of graphene oxide (GO) by glycidyl methacrylated silk fibroin (SB). Compositional analyses showed that SGOB1 contains approximately 8.42% GO in its reduced state. Our results also showed that the rGO content of SGOB1 became more thermally stable and highly soluble. SGOB1 hydrogels demonstrated superior mechanical, electroconductive, and neurogenic properties than (SB). Furthermore, the photocurable bioink supported Neuro2a cell proliferation and viability. Therefore, SGOB1 could be a suitable biocomposite for neural tissue engineering.

FERONIA mutation induces high levels of chloroplast-localized Arabidopsides which are involved in root growth.

The FERONIA (FER) signaling pathway is known to have diverse roles in Arabidopsis thaliana, such as growth, reproduction, and defense, but how this receptor kinase is involved in various biological processes is not well established. In this work, we applied multiple mass spectrometry techniques to identify metabolites involved in the FER signaling pathway and to understand their biological roles. A direct infusion Fourier transform ion cyclotron resonance (FT-ICR)-MS approach was used for initial screening of wild-type and feronia (fer) mutant plant extracts, and Arabidopsides were found to be significantly enriched in the mutant. As Arabidopsides are known to be induced by wounding, further experiments on wounded and non-wounded leaf samples were carried out to investigate these oxylipins as well as related phytohormones using a quadrupole-time-of-flight (Q-TOF) MS by direct injection and LC-MS/MS. In a root growth bioassay with Arabidopside A isolated from fer mutants, the wild-type showed significant root growth inhibition compared with the fer mutant. Our results therefore implicated Arabidopsides, and Arabidopside A specifically, in FER functions and/or signaling. Finally, matrix-assisted laser desorption/ionization MS imaging (MALDI-MSI) was used to visualize the localization of Arabidopsides, and we confirmed that Arabidopsides are highly abundant at wounding sites in both wild-type and fer mutant leaves. More significantly, five micron high-spatial resolution MALDI-MSI revealed that Arabidopsides are localized to the chloroplasts where many stress signaling molecules are made.

Determining Fingerprint Age with Mass Spectrometry Imaging via Ozonolysis of Triacylglycerols.

Despite the common use of fingerprints as a trusted means of identification, no method currently exists to reliably establish the time since deposition of latent fingerprints. A reproducible method of establishing latent fingerprint age would allow forensic personnel to determine if a latent fingerprint was relevant to a crime. This work investigates the ambient aging of triacylglycerols (TGs) and other lipids in latent fingerprint residue utilizing matrix-assisted laser desorption/ionization mass spectrometry imaging. Unsaturated TGs were found to undergo ambient ozonolysis resulting in a decrease over time. At the same time, two series of compounds related to the degradation of unsaturated TGs due to ambient ozonolysis emerged with time and were detectable within a single day of aging. Tracking the degradation of unsaturated TGs over time proved to be relatively reproducible in multiple individuals and is suggested as a means of establishing latent fingerprint age.

Protein arginine methyltransferase-1 stimulates dopaminergic neuronal cell death in a Parkinson's disease model.

Recent studies have revealed that protein arginine methyltransferases (PRMTs) are responsible for diverse neurodegenerative diseases. However, their pathophysiological role in dopaminergic neuronal death in Parkinson's disease (PD) has not been evaluated. In this study, we demonstrated that 1-Methyl-4-phenylpyridinium iodide (MPP+), rotenone and paraquat, which cause dopaminergic neuronal cell death, increased PRMT1 expression in dopaminergic cell line. Dopaminergic neuronal cell death was increased by PRMT1 overexpression. MPP+-induced cell death was attenuated by PRMT1 knockdown. Poly (ADP-ribose) polymerase-1 (PARP1) expression and activity, poly-ADP-ribosylation (PARylation), were elevated by MPP+. Moreover, we found that PRMT1 positively regulates nuclear translocation of apoptosis-inducing factor (AIF). Elevated PRMT1 expression was observed in the substantia nigra pars compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected mice. Furthermore, MPTP-induced dopaminergic neuronal death was reduced in PRMT1 haploinsufficient (prmt1+/-) mice. These data suggest that PRMT1 is implicated in PARP1/AIF-mediated dopaminergic neuronal cell death, which might be involved in the pathology of PD. Therefore, our results propose PRMT1 as a new target to develop a potential treatment of PD.

Development of elastin-like polypeptide for targeted specific gene delivery in vivo.

BACKGROUND: The successful deliveries of siRNA depend on their stabilities under physiological conditions because greater in vivo stability enhances cellular uptake and enables endosomal escape. Viral-based systems appears as most efficient approaches for gene delivery but often compromised in terms of biocompatibility, patient safety and high cost scale up process. Here we describe a novel platform of gene delivery by elastin-like polypeptide (ELP) based targeting biopolymers. RESULTS: For better tumor targeting and membrane penetrating characteristics, we designed various chimeric ELP-based carriers containing a cell penetrating peptide (Tat), single or multiple copies of AP1 an IL-4 receptor targeting peptide along with coding sequence of ELP and referred as Tat-A1E28 or Tat-A4V48. These targeted polypeptides were further analyzed for its ability to deliver siRNA (Luciferase gene) in tumor cells in comparison with non-targeted controls (Tat-E28 or E28). The positively charged amino acids of these polypeptides enabled them to readily complex with negatively charged nucleic acids. The complexation of nucleic acid with respective polypeptides facilitated its transfection efficiency as well as stability. The targeted polypeptides (Tat-A1E28 or Tat-A4V48) selectively delivered siRNA into tumor cells in a receptor-specific fashion, achieved endosomal and lysosomal escape, and released gene into cytosol. The target specific delivery of siRNA by Tat-A1E28 or Tat-A4V48 was further validated in murine breast carcinoma 4T1 allograft mice model. CONCLUSION: The designed delivery systems efficiently delivered siRNA to the target site of action thereby inducing significant gene silencing activity. The study shows Tat and AP1 functionalized ELPs constitute a novel gene delivery system with potential therapeutic applications.