Synergistic intravesical instillation for bladder cancer: CRISPR-Cas13a and fenbendazole combination therapy.

BACKGROUND: CRISPR-Cas13a is renowned for its precise and potent RNA editing capabilities in cancer therapy. While various material systems have demonstrated efficacy in supporting CRISPR-Cas13a to execute cellular functions in vitro efficiently and specifically, the development of CRISPR-Cas13a-based therapeutic agents for intravesical instillation in bladder cancer (BCa) remains unexplored. METHODS: In this study, we introduce a CRISPR-Cas13a nanoplatform, which effectively inhibits PDL1 expression following intravesical instillation. This system utilizes a fusion protein CAST, created through the genetic fusion of CRISPR-Cas13 and the transmembrane peptide TAT. CAST acts as a potent transmembrane RNA editor and is assembled with the transepithelial delivery carrier fluorinated chitosan (FCS). Upon intravesical administration into the bladder, the CAST-crRNAa/FCS nanoparticles (NPs) exhibit remarkable transepithelial capabilities, significantly suppressing PDL1 expression in tumor tissues.To augment immune activation within the tumor microenvironment, we integrated a fenbendazole (FBZ) intravesical system (FBZ@BSA/FCS NPs). This system is formulated through BSA encapsulation followed by FCS coating, positioning FBZ as a powerful chemo-immunological agent. RESULTS: In an orthotropic BCa model, the FBZ@BSA/FCS NPs demonstrated pronounced tumor cell apoptosis, synergistically reduced PDL1 expression, and restructured the immune microenvironment. This culminated in an enhanced synergistic intravesical instillation approach for BCa. Consequently, our study unveils a novel RNA editor nanoagent formulation and proposes a potential synergistic therapeutic strategy. This approach significantly bolsters therapeutic efficacy, holding promise for the clinical translation of CRISPR-Cas13-based cancer perfusion treatments.

A Dopamine-Modified Hyaluronic Acid-Based Mucus Carrying Phytoestrogen and Urinary Exosome for Thin Endometrium Repair.

Thin endometrium (TE) is closely associated with infertility in reproductive medicine. Estrogen therapy gains unsatisfactory outcomes. In this study, an artificial mucus based on dopamine (L-DOPA)-modified hyaluronic acid combining phytoestrogen cajaninstilbene acid and rat urinary exosomes (CUEHD) is constructed for TE treatment using a rat TE model. In the rat TE model, the dominant elastic behavior and adhesive properties of CUEHD guarantee adequate retention, rendering superior synergistic treatment efficacy and favorable biosafety characteristics. CUEHD treatment significantly increases endometrial thickness and promotes receptivity and fertility. Mechanistically, estrogen homeostasis, inflammation inhibition, and endometrial regeneration are achieved through the crosstalk between ER-NLRP3-IL1ß and Wnt-ß catenin-TGFß-smad signaling pathways. Moreover, the therapeutic potential of exosomes from human urine and adipose tissue-derived stem cells (ADSCs) and rat ADSCs are also demonstrated, indicating extensive use of the artificial mucus system. Thus, this study illustrates a platform combining phytoestrogen and exosomes with promising implications for TE treatment.

Partitioning polar-slush strategy in relaxors leads to large energy-storage capability.

Relaxor ferroelectric (RFE) films are promising energy-storage candidates for miniaturizing high-power electronic systems, which is credited to their high energy density (Ue) and efficiency. However, advancing their Ue beyond 200 joules per cubic centimeter is challenging, limiting their potential for next-generation energy-storage devices. We implemented a partitioning polar-slush strategy in RFEs to push the boundary of Ue. Guided by phase-field simulations, we designed and fabricated high-performance Bi(Mg0.5Ti0.5)O3-SrTiO3-based RFE films with isolated slush-like polar clusters, which were realized through suppression of the nonpolar cubic matrix and introduction of highly insulating networks. The simultaneous enhancement of the reversible polarization and breakdown strength leads to a Ue of 202 joules per cubic centimeter with a high efficiency of ~79%. The proposed strategy provides a design freedom for next-generation high-performance dielectrics.

Antibiotic Resistance and Genomic Analysis of Shiga Toxin-Producing Escherichia coli from Dairy Cattle, Raw Milk, and Farm Environment in Shaanxi Province, China.

To investigate the epidemiology of Shiga toxin-producing Escherichia coli (STEC) in dairy cattle, 975 samples (185 feces, 34 silage, 36 cattle drinking water, 360 raw milk, and 360 teat skin swabs) were collected from two dairy farms in Baoji and Yangling, Shaanxi Province, China, and were screened for STEC. Whole-genome sequencing was used to analyze the genomic characteristics and potential transmission of STEC isolates. A total of 32 samples were contaminated with STEC, including 4.0% (19/479) in Farm A and 2.6% (13/496) in Farm B. Compared with adult cows (4.5%), nonadult cows had a higher rate (21.3%) of STEC colonization. A total of 14 serotypes and 11 multilocus sequence typing were identified in 32 STEC isolates, among which O55:H12 (25.0%) and ST101 (31.3%) were the most predominant, respectively. Six stx subtypes/combinations were identified, including stx1a (53.1%), stx2g (15.6%), stx2d, stx2a+stx2d, stx1a+stx2a (6.3%, for each), and stx2a (3.1%). Of 32 STEC isolates, 159 virulence genes and 27 antibiotic resistance genes were detected. Overall, STEC isolates showed low levels of resistance to the 16 antibiotics tested (0-40.6%), with most common resistance to ampicillin (40.6%). The phylogenetic analysis confirmed that STEC in the gut of cattle can be transmitted through feces. The results of this study help to improve our understanding of the epidemiological aspects of STEC in dairy cattle and provide early warning and control of the prevalence and spread of the bacterium.

Collaborative Optimization of Curie Temperature and Piezoelectricity in Ternary BiFeO3-BiScO3-PbTiO3.

The enhancement of piezoelectricity without compromising the Curie temperature of a piezoelectric is challenging due to phenomenological incompatibility. In the present work, the phase diagram of (0.68-x)BiFeO3-xBiScO3-0.32PbTiO3, with varied addition of BiScO3 (x = 0, 0.05, 0.10, 0.15, and 0.20), was constructed through systematic studies of the dielectric, ferroelectric, and piezoelectric properties. A rhombohedral-tetragonal phase boundary was observed near x = 0.10 BiScO3 addition, of which the piezoelectricity was found to be seven times larger than that without BiScO3 (∼208 pm/V vs ∼38 pm/V). Most importantly, a high Curie temperature of 430 °C is successfully inherited from binary 0.68BiFeO3-0.32PbTiO3. This is explained by optimized Bi compensation, which is observed critical regulating Curie temperature in BFO-based binary and ternary systems. These results open up a paradigm for collaboratively optimizing the Curie temperature and piezoelectric response for a number of ferroelectrics and provide a promising BiFeO3-BiScO3-PbTiO3 film with integrated prominent performance for potential applications at elevated temperatures.

The combination of modified acupuncture needle and melittin hydrogel as a novel therapeutic approach for rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) involves chronic joint inflammation. Combining acupuncture and medication for RA treatment faces challenges like spatiotemporal variability, limited drug loading in acupuncture needles, and premature or untargeted drug release. Here, we designed a new type of tubular acupuncture needles, with an etched hollow honeycomb-like structure to enable the high loading of therapeutics, integrating the traditional acupuncture and drug repository into an all-in-one therapeutic platform. In these proof-of-concept experiments, we fabricated injectable hollow honeycomb electroacupuncture needles (HC-EA) loaded with melittin hydrogel (MLT-Gel), enabling the combination treatment of acupuncture stimulation and melittin therapy in a spatiotemporally synchronous manner. Since the RA microenvironment is mildly acidic, the acid-responsive chitosan (CS)/sodium beta-glycerophosphate (ß-GP)/ hyaluronic acid (HA) composited hydrogel (CS/GP/HA) was utilized to perform acupuncture stimulation and achieve the targeted release of injected therapeutics into the specific lesion site. Testing our therapeutic platform involved a mouse model of RA and bioinformatics analysis. MLT-Gel@HC-EA treatment restored Th17/Treg-mediated immunity balance, reduced inflammatory factor release (TNF-α, IL-6, IL-1ß), and alleviated inflammation at the lesion site. This novel combination of modified acupuncture needle and medication, specifically melittin hydrogel, holds promise as a therapeutic strategy for RA treatment.

Total coliforms, microbial diversity and multiple characteristics of Salmonella in soil-irrigation water-fresh vegetable system in Shaanxi, China.

Global occurrences of foodborne disease outbreaks have been documented, involving fresh agricultural produce contaminated by various pathogens. This contamination can occur at any point in the supply chain. However, studies on the prevalence of total coliforms, Salmonella and microbial diversity in vegetable and associated environments are limited. This study aimed to assess 1) the number of total coliforms (n = 299) and diversity of microbial communities (n = 52); 2) the prevalence, antibiotic susceptibility, genomic characteristics, and potential transmission relationships of Salmonella in soil-irrigation water-vegetable system (n = 506). Overall, 84.28 % samples were positive to total coliforms, with most frequently detected in soil (100 %), followed by irrigation water (79.26 %) and vegetables (62.00 %). A seasonal trend in coliform prevalence was observed, with significantly higher levels in summer (P < 0.05). Detection rates of Salmonella in soil, vegetable and irrigation water were 2.21 %, 4.74 % and 9.40 %. Fourteen serotypes and sequence types (STs) were respectively annotated in 56 Salmonella isolates, ST13 S. Agona (30.36 %, 17/56), ST469 S. Rissen (25.00 %, 14/56), and ST36 S. Typhimurium (12.50 %, 7/56) were dominant serotypes and STs. Thirty-one (55.36 %) isolates were multi-drug resistant, and the resistance was most frequently found to ampicillin (55.36 %, 31/56), followed by to sulfamethoxazole (51.79 %, 29/56) and tetracycline (50.00 %, 28/56). The genomic characteristics and antibiotic resistance patterns of Salmonella isolates from soil, vegetables, and irrigation water within a coherent geographical locale exhibited remarkable similarities, indicating Salmonella may be transmitted among these environments or have a common source of contamination. Microbial alpha diversity indices in soil were significantly higher (P < 0.05) than that in vegetable and irrigation water. The microbial phylum in irrigation water covered that in the vegetable, demonstrating a significant overlap in the microbial communities between the vegetables and the irrigation water.

Immune cell-derived extracellular vesicles for precision therapy of inflammatory-related diseases.

Inflammation-related diseases impose a significant global health burden, necessitating urgent exploration of novel treatment modalities for improved clinical outcomes. We begin by discussing the limitations of conventional approaches and underscore the pivotal involvement of immune cells in the inflammatory process. Amidst the rapid growth of immunology, the therapeutic potential of immune cell-derived extracellular vesicles (EVs) has garnered substantial attention due to their capacity to modulate inflammatory response. We provide an in-depth examination of immune cell-derived EVs, delineating their promising roles across diverse disease conditions in both preclinical and clinical settings. Additionally, to direct the development of the next-generation drug delivery systems, we comprehensively investigate the engineered EVs on their advanced isolation methods, cargo loading techniques, and innovative engineering strategies. This review ends with a focus on the prevailing challenges and considerations regarding the clinical translation of EVs in future, emphasizing the need of standardized characterization and scalable production processes. Ultimately, immune cell-derived EVs represent a cutting-edge therapeutic approach and delivery platform, holding immense promise in precision medicine.

Bioresponsive nanocomplex integrating cancer-associated fibroblast deactivation and immunogenic chemotherapy for rebuilding immune-excluded tumors.

Cancer-associated fibroblasts (CAFs) play a crucial role in creating an immunosuppressive environment and remodeling the extracellular matrix within tumors, leading to chemotherapy resistance and limited immune cell infiltration. To address these challenges, integrating CAFs deactivation into immunogenic chemotherapy may represent a promising approach to the reversal of immune-excluded tumor. We developed a tumor-targeted nanomedicine called the glutathione-responsive nanocomplex (GNC). The GNC co-loaded dasatinib, a CAF inhibitor, and paclitaxel, a chemotherapeutic agent, to deactivate CAFs and enhance the effects of immunogenic chemotherapy. Due to the modification with hyaluronic acid, the GNC preferentially accumulated in the tumor periphery and responsively released cargos, mitigating the tumor stroma as well as overcoming chemoresistance. Moreover, GNC treatment exhibited remarkable immunostimulatory efficacy, including CD8+ T cell expansion and PD-L1 downregulation, facilitating immune checkpoint blockade therapy. In summary, the integration of CAF deactivation and immunogenic chemotherapy using the GNC nanoplatform holds promise for rebuilding immune-excluded tumors.

Antibiotic susceptibility and genomic analysis of ciprofloxacin-resistant and ESBLs-producing Escherichia coli in vegetables and their irrigation water and growing soil.

The rise of antibiotic resistance in Escherichia coli has become a major global public health concern. While there is extensive research on antibiotic-resistant E. coli from human and animal sources, studies on vegetables and their environments are limited. This study investigated the prevalence and characteristics of ciprofloxacin-resistant (CIPR) E. coli in 13 types of edible raw vegetables, along with their irrigation water and soil in Shaanxi, China. Of 349 samples collected (157 vegetables, 59 water, and 133 soil), a total of 48 positive samples were detected, with one CIPRE. coli strain isolated from each sample being selected for further analyses. A striking observation was its high prevalence in irrigation water at 44.1 %, markedly exceeding that in vegetables (12.0 %) and soil (4.5 %). The susceptibility of Forty-eight CIPRE. coli isolates was evaluated using the disc diffusion method for 18 different antibiotics, all these isolates were not only resistant to the tested fluoroquinolones antibiotics (levofloxacin, nalidixic acid), but also displayed a multi-drug resistance (MDR) pattern. Twenty-eight (58.3 %) of 48 CIPRE. coli isolates exhibited extended spectrum ß-lactamases (ESBLs) (CIPR-ESBLs) producing phenotype. Subsequently, whole-genome sequencing was performed on these 28 isolates. We identified 12 serotypes and STs each, with O101: H9 (35.7 %, 10/28) and ST10 (21.4 %, 6/28) being the most common. Further classification placed these isolates into five phylogenetic groups: A (57.1 %, 16/28), B1 (32.1 %, 9/28), D (3.6 %, 1/28), B2 (3.6 %,1/28), and F (3.6 %,1/28). Notelly, Identical ST types, serotypes and phylogroups were found in certain CIPR-ESBLs-producing E. coli from both vegetables and adjacent irrigation water. Genomic analysis of the 28 CIPR-ESBLs-producing E. coli isolates unveiled 73 resistance genes, associated with 13 amino acid mutations in resistance-determining regions (QRDRs) and resistance to 12 types of antibiotics. Each isolate was confirmed to carry both ESBLs and fluoroquinolone resistance genes, with the Ser83Ala mutation in GyrA (96.4 %, 27/28) being the most prevalent. A detailed analysis of Mobile Genetic Elements (MGEs) revealed that IncFIB and IncFII plasmid subtypes were most prevalent in 60.7 % and 67.9 % of isolates, respectively, with 75 % containing over 10 insertion sequences (IS) each. Furthermore, we observed that certain ESBL and PMQR genes were located on plasmids or in proximity to insertion sequences. In conclusion, our research highlights the widespread presence of CIPRE. coli in irrigation water and thoroughly examines the genetic characteristics of CIPR-ESBLs-producing E. coli strains, underlining the need for ongoing monitoring and management to reduce multidrug-resistant bacteria in vegetables and their environment.

The efficacy of natural products for the treatment of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant tumor originating in the nasopharyngeal epithelium with a high incidence in southern China and parts of Southeast Asia. The current treatment methods are mainly radiotherapy and chemotherapy. However, they often have side effects and are not suitable for long-term exposure. Natural products have received more and more attention in cancer prevention and treatment because of their its high efficiency, low toxic side effects, and low toxicity. Natural products can serve as a viable alternative, and this study aimed to review the efficacy and mechanisms of natural products in the treatment of NPC by examining previous literature. Most natural products act by inhibiting cell proliferation, metastasis, inducing cell cycle arrest, and apoptosis. Although further research is needed to verify their effectiveness and safety, natural products can significantly improve the treatment of NPC.

Navigating the landscape: Prospects and hurdles in targeting vascular smooth muscle cells for atherosclerosis diagnosis and therapy.

Vascular smooth muscle cells (VSMCs) have emerged as pivotal contributors throughout all phases of atherosclerotic plaque development, effectively dispelling prior underestimations of their prevalence and significance. Recent lineage tracing studies have unveiled the clonal nature and remarkable adaptability inherent to VSMCs, thereby illuminating their intricate and multifaceted roles in the context of atherosclerosis. This comprehensive review provides an in-depth exploration of the intricate mechanisms and distinctive characteristics that define VSMCs across various physiological processes, firmly underscoring their paramount importance in shaping the course of atherosclerosis. Furthermore, this review offers a thorough examination of the significant strides made over the past two decades in advancing imaging techniques and therapeutic strategies with a precise focus on targeting VSMCs within atherosclerotic plaques, notably spotlighting meticulously engineered nanoparticles as a promising avenue. We envision the potential of VSMC-targeted nanoparticles, thoughtfully loaded with medications or combination therapies, to effectively mitigate pro-atherogenic VSMC processes. These advancements are poised to contribute significantly to the pivotal objective of modulating VSMC phenotypes and enhancing plaque stability. Moreover, our paper also delves into recent breakthroughs in VSMC-targeted imaging technologies, showcasing their remarkable precision in locating microcalcifications, dynamically monitoring plaque fibrous cap integrity, and assessing the therapeutic efficacy of medical interventions. Lastly, we conscientiously explore the opportunities and challenges inherent in this innovative approach, providing a holistic perspective on the potential of VSMC-targeted strategies in the evolving landscape of atherosclerosis research and treatment.

Spatiotemporal epidemiology and risk factors of scrub typhus in Hainan Province, China, 2011-2020.

Background: The re-emergence of scrub typhus in the southern provinces of China in recent decades has been validated, thereby attracting the attention of public health authorities. There has been a spatial and temporal expansion of scrub typhus in Hainan Province, but the epidemiological characteristics, environmental drivers, and potential high-risk areas for scrub typhus have not yet been investigated. Objective: The aims of this study were to characterize the spatiotemporal epidemiology of scrub typhus, identify dominant environmental risk factors, and map potential risk areas in Hainan Province from 2011 to 2020. Methods: The spatiotemporal dynamics of scrub typhus in Hainan Province between 2011 and 2020 were analyzed using spatial analyses and seasonal-trend decomposition using regression (STR). The maximum entropy (MaxEnt) model was applied to determine the key environmental predictors and environmentally suitable areas for scrub typhus, and the demographic diversity of the predicted suitable zones was evaluated. Results: During 2011-2020, 3260 scrub typhus cases were recorded in Hainan Province. The number of scrub typhus cases increased continuously each year, particularly among farmers (67.61%) and individuals aged 50-59 years (23.25%) who were identified as high-risk groups. A dual epidemic peak was detected, emerging annually from April to June and from July to October. The MaxEnt-based risk map illustrated that highly suitable areas, accounting for 25.36% of the total area, were mainly distributed in the northeastern part of Hainan Province, where 75.43% of the total population lived. Jackknife tests revealed that ground surface temperature, elevation, cumulative precipitation, evaporation, land cover, population density, and ratio of dependents were the most significant environmental factors. Conclusion: In this study, we gained insights into the spatiotemporal epidemiological dynamics, pivotal environmental drivers, and potential risk map of scrub typhus in Hainan Province. These results have important implications for researchers and public health officials in guiding future prevention and control strategies for scrub typhus.

Cancer-Associated Fibroblast-Induced Remodeling of Tumor Microenvironment in Recurrent Bladder Cancer.

Bladder carcinoma (BC) recurrence is a major clinical challenge, and targeting the tumor microenvironment (TME) is a promising therapy. However, the relationship between individual TME components, particularly cancer-associated fibroblasts (CAFs), and tumor recurrence is unclear. Here, TME heterogeneity in primary and recurrent BC is investigated using single-cell RNA sequence profiling of 62 460 cells. Two cancer stem cell (CSC) subtypes are identified in recurrent BC. An inflammatory CAF subtype, ICAM1+ iCAFs, specifically associated with BC recurrence is also identified. iCAFs are found to secrete FGF2, which acts on the CD44 receptor of rCSC-M, thereby maintaining tumor stemness and epithelial-mesenchymal transition. Additionally, THBS1+ monocytes, a group of myeloid-derived suppressor cells (MDSCs), are enriched in recurrent BC and interacted with CAFs. ICAM1+ iCAFs are found to secrete CCL2, which binds to CCR2 in MDSCs. Moreover, elevated STAT3, NFKB2, VEGFA, and CTGF levels in iCAFs reshape the TME in recurrent tumors. CCL2 inhibition in an in situ BC mouse model suppressed tumor growth, decreased MDSCs and Tregs, and fostered tumor immune suppression. The study results highlight the role of iCAFs in TME cell-cell crosstalk during recurrent BC. The identification of pivotal signaling factors driving BC relapse is promising for the development of novel therapies.

MiR-5189-3p Suppresses cell Proliferation, Invasion and Migration Through Targeting EIF5A2 in Laryngeal Squamous Cell Carcinoma.

A growing body of evidence suggests that miR-5189-3p plays a critical role in multiple diseases. This study aimed to investigate the function of miR-5189-3p in laryngeal squamous cell carcinoma (LSCC) and explore its underlying mechanisms. qRT-PCR was designed to determine the expression levels of miR-5189-3p and eukaryotic translation initiation factor 5A2 (EIF5A2), while CCK-8 assay was performed to measure the effects of miR-5189-3p on cell proliferation. Transwell assay was performed to evaluate cell invasion as well as migration, and wound healing assay was applied to demonstrate cell migratory ability. Target gene prediction and luciferase reporter assay were developed to screen the possible target gene of miR-5189-3p, and Western blot was designed to measure EIF5A2 protein expression. MiR-5189-3p was down-regulated in LSCC tissues and cell lines. Up-regulation of miR-5189-3p notably inhibited cell proliferation, invasion, and migration in HEP2 and FADU cells. EIF5A2 was the potential downstream gene of miR-5189-3p, and overexpression of miR-5189-3p apparently reduced EIF5A2 expression. Moreover, reintroduction of EIF5A2 rescued the tumor suppressive effects of miR-5189-3p. MiR-5189-3p functions as a tumor inhibitor in LSCC progression via directly regulating EIF5A2 and may be a potential therapeutic target for LSCC.

Exosome miR-552 Promotes Laryngocarcinoma Cells Malignant Progression via the PTEN/TOB1 Axis.

INTRODUCTION: Tumor exosome-derived miRNAs play important roles in the human laryngocarcinoma. However, it is still unknown if exosome miR-552 is involved in the laryngocarcinoma. The aim of the current study was to explore exosome miR-552's role in laryngocarcinoma and its underlying mechanisms. METHODS: Hep-2 exosome was characterized by transmission electron microscopy and nanoparticle tracking technology. CCK-8 was used to determine cell viability, and a xenograft animal model was used to determine the tumorigenicity. qPCR and Western blotting were used to measure the changes in target biomarkers. Luciferase reporter assay was used to evaluate the interactions between miR-552 and PTEN. miRNA sequencing was used to check the changes in miRNA profiles. RESULTS: miR-552 was upregulated in the laryngocarcinoma patients and was positively correlated to the cell proliferation and tumor growth. PTEN was identified as a direct target of miR-552. Hep-2 exosome is featured by high expression of miR-552 and treatment of Hep-2 exosome enhanced cell proliferation and tumorigenicity. The underlying mechanisms revealed that treatment of exosomes enhanced the malignant transformation of recipient cells in part by regulating epithelial-mesenchymal transition. CONCLUSION: Exosome miR-552 promotes laryngocarcinoma cells' malignant progression in part by the regulation of the PTEN/TOB1 axis.

Green synthesis of Fe3O4 nanoparticles using Alliaceae waste (Allium sativum) for a sustainable landscape enhancement using support vector regression.

The synthesis of metal nanoparticles using green chemistry methods has gained significant attention in the field of landscape enhancement. Researchers have paid close attention to the development of very effective green chemistry approaches for the production of metal nanoparticles (NPs). The primary goal is to create an environmentally sustainable technique for generating NPs. At the nanoscale, ferro- and ferrimagnetic minerals such as magnetite exhibit superparamagnetic properties (Fe3O4). Magnetic nanoparticles (NPs) have received increased interest in nanoscience and nanotechnology due to their physiochemical properties, small particle size (1-100 nm), and low toxicity. Biological resources such as bacteria, algae, fungus, and plants have been used to manufacture affordable, energy-efficient, non-toxic, and ecologically acceptable metallic NPs. Despite the growing demand for Fe3O4 nanoparticles in a variety of applications, typical chemical production processes can produce hazardous byproducts and trash, resulting in significant environmental implications. The purpose of this study is to look at the ability of Allium sativum, a member of the Alliaceae family recognized for its culinary and medicinal benefits, to synthesize Fe3O4 NPs. Extracts of Allium sativum seeds and cloves include reducing sugars like glucose, which may be used as decreasing factors in the production of Fe3O4 NPs to reduce the requirement for hazardous chemicals and increase sustainability. The analytic procedures were carried out utilizing machine learning as support vector regression (SVR). Furthermore, because Allium sativum is widely accessible and biocompatible, it is a safe and cost-effective material for the manufacture of Fe3O4 NPs. Using the regression indices metrics of root mean square error (RMSE) and coefficient of determination (R2), the X-ray diffraction (XRD) study revealed the lighter, smoother spherical forms of NPs in the presence of aqueous garlic extract and 70.223 nm in its absence. The antifungal activity of Fe3O4 NPs against Candida albicans was investigated using a disc diffusion technique but exhibited no impact at doses of 200, 400, and 600 ppm. This characterization of the nanoparticles helps in understanding their physical properties and provides insights into their potential applications in landscape enhancement.

Self-assembled thioether-bridged paclitaxel-dihydroartemisinin prodrug for amplified antitumor efficacy-based cancer ferroptotic-chemotherapy.

Ferroptosis has been proposed as one form of iron-dependent cell death, overgeneration of high-toxicity hydroxyl radicals (˙OH) tumor sites via Fenton reactions induced cell membrane damage. However, the insufficient intracellular concentrations of both iron and H2O2 limited the anticancer performance of ferroptosis. In this study, ROS-sensitive prodrug nanoassemblies composed of a PEG2000-ferrous compound and a single thioether bond bridged dihydroartemisinin-paclitaxel prodrug were constructed, which fully tapped ex/endogenous iron, ferroptosis inducers, and chemotherapeutic agents. Following cellular uptake, the intracellular oxidizing environment accelerated the self-destruction of nanoassemblies and triggered drug release. In addition to the chemotherapeutic effect, the activated dihydroartemisinin was capable of acting as a toxic ˙OH amplifier via the reinforced Fenton reaction, simultaneously depleting intracellular GSH, as well as inducing glutathione peroxidase 4 inactivation, further enhancing ferroptosis-dependent cancer cell proliferation inhibition. Meanwhile, the ROS generation-inductive and cell cycle arrest effect from the paclitaxel augmented synergetic ferroptotic-chemotherapy of cancer. Thus, the prodrug integrating dihydroartemisinin with paclitaxel via a single thioether bond represents a potent nanoplatform to exert amplified ferroptotic-chemotherapy for improved anticancer efficacy.

Tuning Piezoelectricity via Thermal Annealing at a Freestanding Ferroelectric Membrane.

Tuning the ferroelectric domain structure by a combination of elastic and electrostatic engineering provides an effective route for enhanced piezoelectricity. However, for epitaxial thin films, the clamping effect imposed by the substrate does not allow aftergrowth tuning and also limits the electromechanical response. In contrast, freestanding membranes, which are free of substrate constraints, enable the tuning of a subtle balance between elastic and electrostatic energies, giving new platforms for enhanced and tunable functionalities. Here, highly tunable piezoelectricity is demonstrated in freestanding PbTiO3 membranes, by varying the ferroelectric domain structures from c-dominated to c/a and a domains via aftergrowth thermal treatment. Significantly, the piezoelectric coefficient of the c/a domain structure is enhanced by a factor of 2.5 compared with typical c domain PbTiO3. This work presents a new strategy to manipulate the piezoelectricity in ferroelectric membranes, highlighting their great potential for nano actuators, transducers, sensors and other NEMS device applications.