Mechanistic insights into tris(2-chloroisopropyl) phosphate biomineralization coupled with lead (II) biostabilization driven by denitrifying bacteria.

The ubiquity and persistence of organophosphate esters (OPEs) and heavy metal (HMs) pose global environmental risks. This study explored tris(2-chloroisopropyl)phosphate (TCPP) biomineralization coupled to lead (Pb2+) biostabilization driven by denitrifying bacteria (DNB). The domesticated DNB achieved synergistic bioremoval of TCPP and Pb2+ in the batch bioreactor (efficiency: 98 %).TCPP mineralized into PO43- and Cl-, and Pb2+ precipitated with PO43-. The TCPP-degrading/Pb2+-resistant DNB: Achromobacter, Pseudomonas, Citrobacter, and Stenotrophomonas, dominated the bacterial community, and synergized TCPP biomineralization and Pb2+ biostabilization. Metagenomics and metaproteomics revealed TCPP underwent dechlorination, hydrolysis, the TCA cycle-based dissimilation, and assimilation; Pb2+ was detoxified via bioprecipitation, bacterial membrane biosorption, EPS biocomplexation, and efflux out of cells. TCPP, as an initial donor, along with NO3-, as the terminal acceptor, formed a respiratory redox as the primary energy metabolism. Both TCPP and Pb2+ can stimulate phosphatase expression, which established the mutual enhancements between their bioconversions by catalyzing TCPP dephosphorylation and facilitating Pb2+ bioprecipitation. TCPP may alleviate the Pb2+-induced oxidative stress by aiding protein phosphorylation. 80 % of Pb2+ converted into crystalized pyromorphite. These results provide the mechanistic foundations and help develop greener strategies for synergistic bioremediation of OPEs and HMs.

Psychometric evaluation of the Chinese version of the febrile convulsion knowledge scale for parents/caregivers: translation and validation study.

BACKGROUND: Fever is one of the most common clinical symptoms of respiratory diseases in children. Once the child has a fever, parents and caregivers are mainly concerned that the child may have a febrile convulsion. A lack of cognitive ability not only leads to anxiety but also aggravates or delays the time of children's medical treatment and even seriously affects the prognosis because of improper management of fever patients.Therefore, it is necessary to clarify the degree of mastery of knowledge related to febrile convulsions, implement targeted guidance and health education, and ensure that parents and caregivers receive correct and reasonable first aid treatment. The purpose of this study was to translate the Febrile Convulsion Knowledge Scale for Parents/Caregivers into Chinese and to verify its reliability and validity for Chinese parents and caregivers of children. METHODS: The Brislin traditional translation model was used to translate the Febrile Convulsion Knowledge Scale for Parents/Caregivers from English to Chinese, following authorization from the original author of the scale. This involved literal translation, back translation, and cultural adaptation. A convenience sampling method was used to select 402 parents and caregivers of children in the pediatric ward and pediatric infusion clinic of a Grade III hospital in Liaoning Province. The item analysis method was employed to assess item differentiation, while the Delphi method was used to analyze content validity. Scale reliability was evaluated through the calculation of internal consistency and test-retest reliability. Exploratory and confirmatory factor analyses were conducted to explore and verify the underlying factor structure and scale validity. RESULTS: The Chinese version of the Febrile Convulsion Knowledge Scale for Parents/Caregivers consists of 3 dimensions and 8 items. The Cronbach's alpha coefficient was 0.828, with each dimension having coefficients of 0.806, 0.720, and 0.702. The split-half reliability and test-retest reliability were 0.716 and 0.790, respectively. The Chinese version has good reliability. Exploratory factor analysis revealed that the Bartlett sphericity test was 394.52 (p < 0.001) and that the KMO value was 0.802 > 0.600, indicating suitability for factor analysis. Principal component analysis and orthogonal rotation of maximum variance were performed on the data, and items with a load greater than 0.40 within a single factor were selected for inclusion. The resulting three-factor structure explained 70.78% of the total variance. All model fitting indices were within the acceptable range, indicating the good structural validity of the Chinese version. The results of both exploratory and confirmatory factor analyses support this conclusion. CONCLUSIONS: The Chinese version of the Febrile Convulsion Knowledge Scale for Parents/Caregivers has good reliability and validity. It can be used as a tool for clinical pediatric nurses to evaluate the knowledge of parents and caregivers of children with febrile convulsion and provide the basis for the design and implementation of targeted training plans according to the results obtained from the Chinese scale.

Impulsivity is a stable, measurable, and predictive psychological trait.

Impulsivity is a personality construct frequently employed to explain and predict important human behaviors. Major inconsistencies in its definition and measurement, however, have led some researchers to call for an outright rejection of impulsivity as a psychological construct. We address this highly unsatisfactory state with a large-scale, preregistered study (N = 1,676) in which each participant completed 48 measures of impulsivity derived from 10 self-report scales and 10 behavioral tasks and reported frequencies of seven impulsivity-related behaviors (e.g., impulsive buying and social media usage); a subsample (N = 196) then completed a retest session 3 mo later. We found that correlations between self-report measures were substantially higher than those between behavioral tasks and between self-report measures and behavioral tasks. Bifactor analysis of these measures exacted one general factor of impulsivity I, akin to the general intelligence factor g, and six specific factors. Factor I was related mainly to self-report measures, had high test-retest reliability, and could predict impulsivity-related behaviors better than existing measures. We further developed a scale named the adjustable impulsivity scale (AIMS) to measure I. AIMS possesses excellent psychometric properties that are largely retained in shorter versions and could predict impulsivity-related behaviors equally well as I. These findings collectively support impulsivity as a stable, measurable, and predictive trait, indicating that it may be too early to reject it as a valid and useful psychological construct. The bifactorial structure of impulsivity and AIMS, meanwhile, significantly advance the conceptualization and measurement of construct impulsivity.

Carrier-free self-assembled nanoparticles based on prochloraz and fenhexamid for reducing toxicity to aquatic organism.

Nanoformulations of pesticides are an effective way to increase utilization efficiency and alleviate the adverse impacts on the environments caused by conventional pesticide formulations. However, the complex preparation process, high cost, and potential environmental risk of nanocarriers severely restricted practical applications of carrier-based pesticide nanoformulations in agriculture. Herein, carrier-free self-assembled nanoparticles (FHA-PRO NPs) based on fenhexamid (FHA) and prochloraz (PRO) were developed by a facile co-assembly strategy to improve utilization efficiency and reduce toxicity to aquatic organism of pesticides. The results showed that noncovalent interactions between negatively charged FHA and positively charged PRO led to core-shell structured nanoparticles arranged in an orderly manner dispersing in aqueous solution with a diameter of 256 nm. The prepared FHA-PRO NPs showed a typical pH-responsive release profile and exhibited excellent physicochemical properties including low surface tension and high max retention. The photostability of FHA-PRO NPs was improved 2.4 times compared with free PRO. The FHA-PRO NPs displayed superior fungicidal activity against Sclerotinia sclerotiorum and Botrytis cinerea and longer duration against Sclerotinia sclerotiorum on potted rapeseed plants. Additionally, the FHA-PRO NPs reduced the acute toxicity of PRO to zebrafish significantly. Therefore, this work provided a promising strategy to develop nanoformulations of pesticides with stimuli-responsive controlled release characteristics for precise pesticide delivery.

Hallmarks of cancer resistance.

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. The role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are studied. The chapter emphasizes future directions, encompassing advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches, aiming to navigate the complex landscape of cancer resistance and enhance patient outcomes.

Parecoxib inhibits tumorigenesis and angiogenesis in hepatocellular carcinoma through ERK-VEGF/MMPs signaling pathway.

Parecoxib, a well-recognized nonsteroidal anti-inflammatory drug, has been reported to possess anticancer properties in various tumor types. In this work, we aimed to investigate the potential anticancer effects of parecoxib on hepatocellular carcinoma (HCC) cells. To assess the impact of parecoxib on HCC cell proliferation, we employed Cell Counting Kit-8, colony formation, and 5-ethynyl-2'-deoxyuridine assays. Hoechst/propidium iodide (PI) double staining and flow cytometry were performed to evaluate apoptosis and cell cycle analysis. Wound healing and transwell assays were utilized to assess cell migration and invasion. Tube formation assay was employed to analyze angiogenesis. Protein levels were determined using western blotting, and mRNA expression levels were assessed using quantitative real-time polymerase chain reaction (PCR). A xenograft mouse model was used to confirm the antitumor effects of parecoxib on HCC tumors in vivo. Our data demonstrated that parecoxib effectively inhibited the proliferation of HCC cells in a dose- and time-dependent manner. In addition, parecoxib induced cell cycle arrest in the G2 phase and promoted apoptosis. Moreover, parecoxib hindered tumor migration and invasion by impeding the epithelial-mesenchymal transition process. Further investigation showed that parecoxib could significantly suppress angiogenesis through the inhibition of extracellular signal-regulated kinase (ERK)-vascular endothelial growth factor (VEGF) axis. Notably, treatment with the ERK activator phorbol myristate acetate upregulated the expression of matrix metalloproteinase (MMP)-2, MMP-9, and VEGF and reversed the function of parecoxib in HCC cells. Besides, parecoxib displayed its antitumor efficacy in vivo. Collectively, our results suggest that parecoxib ameliorates HCC progression by regulating proliferation, cell cycle, apoptosis, migration, invasion, and angiogenesis through the ERK-VEGF/MMPs signaling pathway.

Developing trustworthy artificial intelligence: insights from research on interpersonal, human-automation, and human-AI trust.

The rapid advancement of artificial intelligence (AI) has impacted society in many aspects. Alongside this progress, concerns such as privacy violation, discriminatory bias, and safety risks have also surfaced, highlighting the need for the development of ethical, responsible, and socially beneficial AI. In response, the concept of trustworthy AI has gained prominence, and several guidelines for developing trustworthy AI have been proposed. Against this background, we demonstrate the significance of psychological research in identifying factors that contribute to the formation of trust in AI. Specifically, we review research findings on interpersonal, human-automation, and human-AI trust from the perspective of a three-dimension framework (i.e., the trustor, the trustee, and their interactive context). The framework synthesizes common factors related to trust formation and maintenance across different trust types. These factors point out the foundational requirements for building trustworthy AI and provide pivotal guidance for its development that also involves communication, education, and training for users. We conclude by discussing how the insights in trust research can help enhance AI's trustworthiness and foster its adoption and application.

Diagnostic value associated with the combination of saliva pepsin and microorganisms in functional heartburn and gastroesophageal reflux disease.

Heartburn is a common symptom shared by both gastroesophageal reflux disease (GERD) and functional heartburn (FHB), which can make it challenging to differentiate between the two conditions. However, examining oral manifestations of GERD can be a cost-effective and readily available method to aid in this differentiation process. It may serve as a valuable tool in distinguishing GERD from FHB.

A Stimulus-Responsive Ternary Heterojunction Boosting Oxidative Stress, Cuproptosis for Melanoma Therapy.

Cuproptosis, a recently discovered copper-dependent cell death, presents significant potential for the development of copper-based nanoparticles to induce cuproptosis in cancer therapy. Herein, a unique ternary heterojunction, denoted as HACT, composed of core-shell Au@Cu2O nanocubes with surface-deposited Titanium Dioxide quantum dots and modified with hyaluronic acid is introduced. Compared to core-shell AC NCs, the TiO2/Au@Cu2O exhibits improved energy structure optimization, successfully separating electron-hole pairs for redox use. This optimization results in a more rapid generation of singlet oxygen and hydroxyl radicals triggering oxidative stress under ultrasound radiation. Furthermore, the HACT NCs initiate cuproptosis by Fenton-like reaction and acidic environment, leading to the sequential release of cupric and cuprous ions. This accumulation of copper induces the aggregation of lipoylated proteins and reduces iron-sulfur proteins, ultimately initiating cuproptosis. More importantly, HACT NCs show a tendency to selectively target cancer cells, thereby granting them a degree of biosecurity. This report introduces a ternary heterojunction capable of triggering both cuproptosis and oxidative stress-related combination therapy in a stimulus-responsive manner. It can energize efforts to develop effective melanoma treatment strategies using Cu-based nanoparticles through rational design.

Role of arylalkylamine N-acetyltransferase 7 in reproduction and limb pigmentation of Aedes aegypti.

Arylalkylamine N-acetyltransferase (aaNAT) is a crucial enzyme that catalyses the transfer of acetyl groups from acetyl coenzyme A to arylalkylamines and arylamines. Evolutionary studies have identified a distinct class of aaNATs specific to mosquitoes, yet their functions remain elusive. This study focuses on Ae-aaNAT7, a mosquito-unique gene in Aedes aegypti (Diptera:Culicidae), to explore its functionality. Temporal and spatial expression analysis of Ae-aaNAT7 mRNA revealed high expression during embryonic development and in first-instar larvae, with notable expression in the limbs of adult mosquitoes based on tissue expression profiling. By further employing CRISPR/Cas9 technology for loss-of-function studies, our investigation revealed a reduction in the area of white spotting in the limbs of Ae-aaNAT7 mutant adult mosquitoes. Further investigation revealed a significant decrease in the fecundity and hatchability of the mutants. Dissection of the ovaries from Ae-aaNAT7 heterozygous mutants showed a noticeable reduction in the oocyte area compared with wild type. Dissection of the exochorion of the eggs from Ae-aaNAT7 homozygous mutants consistently revealed a striking absence of mature embryos. In addition, RNA interference experiments targeting Ae-aaNAT7 in males resulted in a reduction in fecundity, but no effect on hatchability was observed. These collective insights underscore the substantial impact of Ae-aaNAT7 on reproduction and its pivotal contribution to adult limb pigmentation in Ae. aegypti. These revelations offer insights pivotal for the strategic design of future insecticide targets.

Ternary heterostructure-driven photoinduced electron-hole separation enhanced oxidative stress for triple-negative breast cancer therapy.

Zinc oxide nanoparticles (ZnO NPs) stand as among the most significant metal oxide nanoparticles in trigger the formation of reactive oxygen species (ROS) and induce apoptosis. Nevertheless, the utilization of ZnO NPs has been limited by the shallowness of short-wavelength light and the constrained production of ROS. To overcome these limitations, a strategy involves achieving a red shift towards the near-infrared (NIR) light spectrum, promoting the separation and restraining the recombination of electron-hole (e--h+) pairs. Herein, the hybrid plasmonic system Au@ZnO (AZ) with graphene quantum dots (GQDs) doping (AZG) nano heterostructures is rationally designed for optimal NIR-driven cancer treatment. Significantly, a multifold increase in ROS generation can be achieved through the following creative initiatives: (i) plasmonic Au nanorods expands the photocatalytic capabilities of AZG into the NIR domain, offering a foundation for NIR-induced ROS generation for clinical utilization; (ii) elaborate design of mesoporous core-shell AZ structures facilitates the redistribution of electron-hole pairs; (iii) the incorporation GQDs in mesoporous structure could efficiently restrain the recombination of the e--h+ pairs; (iv) Modification of hyaluronic acid (HA) can enhance CD44 receptor mediated targeted triple-negative breast cancer (TNBC). In addition, the introduced Au NRs present as catalysts for enhancing photothermal therapy (PTT), effectively inducing apoptosis in tumor cells. The resulting HA-modified AZG (AZGH) exhibits efficient hot electron injection and e--h+ separation, affording unparalleled convenience for ROS production and enabling NIR-induced PDT for the cancer treanment. As a result, our well-designed mesoporous core-shell AZGH hybrid as photosensitizers can exhibit excellent PDT efficacy.

Psychometric properties of the Chinese version of the oncology nurses health behaviors determinants scale: a cross-sectional study.

Objective: To test the validity and reliability of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON) in oncology nurses, the Chinese version was developed. Methods: The Brislin double translation-back translation approach was employed to forward translation, back translation, synthesis, cross-cultural adaptation, and pre-survey, resulting in the first Chinese version of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON). A convenience sample technique was used to select 350 study participants in Liaoning, Shandong, and Jiangsu, China, who satisfied the inclusion and exclusion criteria, to assess the validity and reliability of the scale. Results: The Chinese version of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON) had six subscales (perceived threat, perceived benefits, perceived barriers, self-efficacy, cues to action, and personal protective equipment availability and accessibility), including 29 items. The average scale level was 0.931, and the content validity level of the items varied from 0.857 to 1.000. Each Cronbach's α coefficient had an acceptable internal consistency reliability range of 0.806 to 0.902. X2/df = 1.667, RMSEA = 0.044, RMR = 0.018, CFI = 0.959, NFI = 0.905, TLI = 0.954, and IFI = 0.960 were the model fit outcomes in the validation factor analysis. All of the model fit markers fell within reasonable bounds. Conclusion: The Chinese version of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON) has good reliability and validity and can be used as a tool to assess the influencing factors of chemotherapy exposure for oncology nurses in China.

MDR49 coding for both P-glycoprotein and TMOF transporter functions in ivermectin resistance, trypsin activity inhibition, and fertility in the yellow fever mosquito, Aedes aegypti.

This study investigated the function of the MDR49 gene in Aedes aegypti. MDR49 mutants were constructed using CRISPR/Cas9 technology; the mutation led to increased sensitivity to ivermectin (LC50: from 1.3090 mg L-1 to 0.5904 mg L-1), and a reduction in midgut trypsin activity. These findings suggest that the P-gp encoded by MDR49 confers resistance to ivermectin and impacts the reproductive function in Ae. aegypti. RNA interference technology showed that knockdown of MDR49 gene resulted in a significant decrease in the expression of VGA1 after a blood meal, as well as a decrease in the number of eggs laid and their hatching rate. LC-MS revealed that following ivermectin treatment, the MDR493d+2s/3d+2s strain larvae exhibited significantly higher drug concentrations in the head and fat body compared to the wild type. Modeling of inward-facing P-gp and molecular docking found almost no difference in the affinity of P-gp for ivermectin before and after the mutation. However, modeling of the outward-facing conformation demonstrated that the flexible linker loop between TM5 and TM6 of P-gp undergoes changes after the mutation, resulting in a decrease in trypsin activity and an increase in sensitivity to ivermectin. These results provide useful insights into ivermectin resistance and the other roles played by the MDR49 gene.

Importance of DNA nanotechnology for DNA methyltransferases in biosensing assays.

DNA methylation is the process by which specific bases on a DNA sequence acquire methyl groups under the catalytic action of DNA methyltransferases (DNMT). Abnormal changes in the function of DNMT are important markers for cancers and other diseases; therefore, the detection of DNMT and the selection of its inhibitors are critical to biomedical research and clinical practice. DNA molecules can undergo intermolecular assembly to produce functional aggregates because of their inherently stable physical and chemical properties and unique structures. Conventional DNMT detection methods are cumbersome and complicated processes; therefore, it is necessary to develop biosensing technology based on the assembly of DNA nanostructures to achieve rapid analysis, simple operation, and high sensitivity. The design of the relevant program has been employed in life science, anticancer drug screening, and clinical diagnostics. In this review, we explore how DNA assembly, including 2D techniques like hybridization chain reaction (HCR), rolling circle amplification (RCA), catalytic hairpin assembly (CHA), and exponential isothermal amplified strand displacement reaction (EXPAR), as well as 3D structures such as DNA tetrahedra, G-quadruplexes, DNA hydrogels, and DNA origami, enhances DNMT detection. We highlight the benefits of these DNA nanostructure-based biosensing technologies for clinical use and critically examine the challenges of standardizing these methods. We aim to provide reference values for the application of these techniques in DNMT analysis and early cancer diagnosis and treatment, and to alert researchers to challenges in clinical application.

An enzymatically activated AND-gate DNA logic circuit for tumor cells recognition via multi-microRNAs detection.

The DNA-based logic circuit, constructed to mimic biochemical reaction networks, is highly significant in detecting biomarkers at the molecular level. The differences in the expression levels of microRNAs (miRNAs) within different types of cells provide hope for distinguishing cell subtypes. However, reliance on a single miRNA often leads to unreliable results. Herein, we constructed an enzyme-triggered cascade logic circuit based on the AND gate, which is capable of generating corresponding fluorescence signals in the presence of target miRNAs. The introduction of apurinic/apyrimidinic (AP) sites effectively reduces the likelihood of false signal generation. Amplification of the fluorescence signal relies on the catalytic hairpin assembly and the repetitive reuse of the multicomponent nucleic acid enzyme (MNAzyme). We demonstrated that the logic circuit can not only distinguish cancer cells from normal cells but also identify different types of cancer cells. The programmability of the logic circuits and the simplicity of the assay system allow us to modify the functional sequences to recognize different types of biomarkers, thus providing a reference for the identification of various cell subtypes.

Leveraging Bayesian network to reveal the importance of water level in a shallow lake ecosystem: A study based on Paleo-diatom and fish community.

Lake ecological processes and nutrient patterns are increasingly affected by water level variation around the world. Still, the long-term effects of water level change on lake ecosystems and their implications for suitable lake level management have rarely been studied. Here, we studied the ecosystem dynamics of a mesotrophic lake located in the cold and arid region of northern China based on long-term paleo-diatom and fishery records. Utilizing a novel Copula-Bayesian Network model, possible hydrological-driven ecosystem evolution was discussed. Results show that increased nutrient concentration caused by the first water level drop in the early 1980s incurred a transition of sedimental diatoms towards pollution-resistant species, and the following water level rise in the mid-1980s brought about considerable external loading, which attributed to eutrophication and caused the miniaturization of fishery structure. In the 21st century, a continuous water level plummet further reduced the sediment diatom biomass and the fish biomass by altering nutrient concentration. However, with the implementation of the water diversion project in 2011, oligotrophic species increased, and the ecosystem developed for the better. From the perspective of water quality protection requirements and the ecological well-being of Lake Hulun, the appropriate water level should be around 542.42-544.15 m. In summary, our study highlights the coupling effect of water level and water quality on Lake Hulun ecosystem and gives shed to lake water level operation and management under future climate change and human activities.

The application of drug behavior management methods in the treatment of dental fear and oral diseases in children: A review.

Oral behavior management methods include basic behavior management methods and drug behavior management methods. In many cases, dental treatment that cannot be done simply through basic behavior management is not possible. The uncooperative behavior of children with dental fear in oral treatment has increased the demand for medication based behavior management methods. Drug sedation can provide more effective analgesic and anti-anxiety effects, thereby helping to provide comfortable, efficient, and high-quality dental services. This article will review the drug sedation methods selected in clinical treatment of pediatric dental fear in recent years, as well as the safety and effectiveness of commonly used drugs, in order to provide guidance for dental professionals in clinical practice.

Disposable Plastic Waste and Associated Antioxidants and Plasticizers Generated by Online Food Delivery Services in China: National Mass Inventories and Environmental Release.

China's online food delivery (OFD) services consume enormous amounts of disposable plastics. Here, we investigated and modeled the national mass inventories and environmental release of plastics and chemical additives in the plastic. The extra-tree regression identified six key descriptors in determining OFD sales in Chinese cities. Approximately 847 kt of OFD plastic waste was generated in 2021 (per capita 1.10 kg/yr in the megacities and 0.39 kg/yr in other cities). Various additives were extensively detected, with geomean concentrations of 140.96, 4.76, and 0.25 µg/g for ∑8antioxidants, ∑21phthalates, and bisphenol A (BPA), respectively. The estimated mass inventory of these additives in the OFD plastics was 164.7 t, of which 51.1 t was released into the atmosphere via incineration plants and 51.0 t was landfilled. The incineration also released 8.07 t of polycyclic aromatic hydrocarbons and 39.1 kt of particulate matter into the atmosphere. Takeout food may increase the dietary intake of phthalates and BPA by 30% to 50% and raise concerns about considerable exposure to antioxidant transformation products. This study provides profound environmental implications for plastic waste in the Chinese OFD industry. We call for a sustainable circular economy action plan for waste disposal, but mitigating the hazardous substance content and their emissions is urgent.

A proteomic landscape of pharmacologic perturbations for functional relevance.

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Gelatin-Encapsulated Tetrahedral DNA Nanostructure Enhances Cellular Internalization for Treating Noise-Induced Hearing Loss.

Nanoparticle-based drug delivery strategies have emerged as a crucial avenue for comprehensive sensorineural hearing loss treatment. Nevertheless, developing therapy vectors crossing both biological and cellular barriers has encountered significant challenges deriving from various external factors. Herein, the rational integration of gelatin nanoparticles (GNPs) with tetrahedral DNA nanostructures (TDNs) to engineer a distinct drug-delivery nanosystem (designed as TDN@GNP) efficiently enhances the biological permeability and cellular internalization, further resolving the dilemma of noise-induced hearing loss via loading epigallocatechin gallate (EGCG) with anti-lipid peroxidation property. Rationally engineering of TDN@GNP demonstrates dramatic alterations in the physicochemical key parameters of TDNs that are pivotal in cell-particle interactions and promote cellular uptake through multiple endocytic pathways. Furthermore, the EGCG-loaded nanosystem (TDN-EGCG@GNP) facilitates efficient inner ear drug delivery by superior permeability through the biological barrier (round window membrane), maintaining high drug concentration within the inner ear. The TDN-EGCG@GNP actively overcomes the cell membrane, exhibiting hearing protection from noise insults via reduced lipid peroxidation in outer hair cells and spiral ganglion neurons. This work exemplifies how integrating diverse vector functionalities can overcome biological and cellular barriers in the inner ear, offering promising applications for inner ear disorders.