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DNA origami-based nanorobot presents thrombin to cause tumor infarction after specific recognition of a tumor vessel marker. Nanoscale robots have potential as intelligent drug delivery systems that respond to molecular triggers 1 , 2 , 3 , 4 . Using DNA origami we constructed an autonomous DNA robot programmed to transport payloads and present them specifically in tumors. Our nanorobot is functionalized on the outside with a DNA aptamer that binds nucleolin, a protein specifically expressed on tumor-associated endothelial cells 5 , and the blood coagulation protease thrombin within its inner cavity. The nucleolin-targeting aptamer serves both as a targeting domain and as a molecular trigger for the mechanical opening of the DNA nanorobot. The thrombin inside is thus exposed and activates coagulation at the tumor site. Using tumor-bearing mouse models, we demonstrate that intravenously injected DNA nanorobots deliver thrombin specifically to tumor-associated blood vessels and induce intravascular thrombosis, resulting in tumor necrosis and inhibition of tumor growth. The nanorobot proved safe and immunologically inert in mice and Bama miniature pigs. Our data show that DNA nanorobots represent a promising strategy for precise drug delivery in cancer therapy.

Since the discovery of metal nanoparticles (NPs) in the 1960s, unknown toxicity, cost and the ethical hurdles of research in humans have hindered the translation of these NPs to clinical use. In this work, we demonstrate that Pt NPs with protein coronas are generated in vivo in human blood when a patient is treated with cisplatin. These self-assembled Pt NPs form rapidly, accumulate in tumors, and remain in the body for an extended period of time. Additionally, the Pt NPs are safe for use in humans and can act as anti-cancer agents to inhibit chemotherapy-resistant tumor growth by consuming intracellular glutathione and activating apoptosis. The tumor inhibitory activity is greatly amplified when the Pt NPs are loaded in vitro with the chemotherapeutic drug, daunorubicin, and the formulation is effective even in daunorubicin-resistant models. These in vivo-generated metal NPs represent a biocompatible drug delivery platform for chemotherapy resistant tumor treatment. Platinum based drugs like cisplatin are common chemotherapy treatments for cancer. Here, the authors report on the in situ formation of platinum nanoparticles in patients and demonstrated how platinum nanoparticles can be synthesized using patients’ blood and provide effective drug delivery and cancer treatments.

Background Gestational diabetes mellitus (GDM) is a common pregnancy complication with far-reaching implications for maternal and offspring health, strongly tied to epigenetic modifications, particularly DNA methylation. However, the precise molecular mechanisms by which GDM increases long-term metabolic disease risk in offspring remain insufficiently understood. Methods We integrated multiple publicly available whole-genome methylation datasets focusing on neonates born to mothers with GDM. Using differentially methylated positions (DMPs) identified in these datasets, we developed a machine learning model to predict GDM-associated epigenetic changes, then validated its performance in a clinical target cohort. Results In the public datasets, we identified DMPs corresponding to genes involved in glucose homeostasis and insulin sensitivity, with marked enrichment in insulin signaling, AMPK activation, and adipocytokine signaling pathways. The predictive model exhibited strong performance in public data (AUC = 0.89) and moderate performance in the clinical cohort (AUC = 0.82). Although CpG sites in the PPARG and INS genes displayed similar methylation trends in both datasets, the small validation cohort did not yield statistically significant differences. Conclusions By integrating robust public data with a targeted validation cohort, this study provides a comprehensive epigenetic profile of GDM-exposed offspring. Owing to the limited sample size and lack of statistical significance, definitive conclusions cannot yet be drawn; however, the observed directional consistency suggests promising avenues for future research. Larger and more diverse cohorts are warranted to confirm these preliminary findings, clarify their clinical implications, and enhance early risk assessment for metabolic disorders in children born to GDM mothers.

In biological systems, molecular network functionalities are usually switched in a flexible, facile, and programmable manner. Mimicking this, substantial studies are directed towards developing synthetic DNA networks that exhibit similar function-switching capabilities, though often hindered by extensive molecular architecture changes and stringent condition controls, which result in a time-consuming and labor-intensive process. Here, we develop a base stacking-mediated allostery strategy to manipulate the DNA computing function switching with minimal molecular architecture changes, usually as few as 1-2 nucleotide changes. We implement up to 20 distinct logic function switching within DNAzyme networks. We also validate our function switching platform to implement totally 84 kinds of gene regulation patterns in cancer cell lines, demonstrating its utility in RNA sensing and green fluorescent protein regulation. This strategy offers a simplified alternative approach to enrich DNA regulations, with potential applications in DNA computing and bioengineering. DNA computing systems face challenges in switching functions due to complex molecular redesigns. Here, the authors introduce a base Stacking-Mediated Allostery (SMALL) strategy enabling efficient function switching with minimal architecture changes (1-2 nucleotides), implemented across diverse logic operations and cellular gene regulation patterns.

Background Hepatocellular carcinoma (HCC) is among the deadliest cancers due to its heterogeneity, contributing to chemoresistance and recurrence. Cancer stem-like cells (CSCs) are suggested to play an important role in HCC tumorigenesis. This study investigates the role of Wnt/β-catenin pathway in CSC enrichment and the capabilities of these CSCs in tumor initiation in orthotopic immunocompetent mouse model. Methods HCC-CSCs were enriched using established serum-free culture method. Wnt/β-catenin pathway activation and its components were analyzed by western blot and qRT-PCR. The role of β-catenin in enrichment of CSC spheroids was confirmed using siRNA interference. Tumorigenic capabilities were confirmed using orthotopic immunocompetent mouse model by injecting 2 × 10 6 Hepa1–6 CSC spheroids or control cells in upper left liver lobe. Results The serum-free cultured Hepa1–6 cells demonstrated self-renewal, spheroid formation, higher EpCAM expression, increased Hoechst-33342 efflux, and upregulated Wnt/β-catenin signaling. Wnt/β-catenin pathway upregulation was implicated with the downstream targets, i.e., c-MYC, Cyclin-D1, and LEF1. Also, we found that GSK-3β serine-9 phosphorylation increased in Hepa1–6 spheroids. Silencing β-catenin by siRNA reversed spheroid formation phenotype. Mice injected with Hepa1–6 CSC spheroids showed aggressive tumor initiation and growth compared with mice injected with control cells. Conclusions Successfully induced Hepa1–6 spheroids were identified with CSC-like properties. Aberrant β-catenin upregulation mediated by GSK-3β was observed in the Hepa1–6 spheroids. The β-catenin mediated CSC enrichment in the induced spheroids possesses the capability of tumor initiation in immunocompetent mice. Our study suggests plausible cell dedifferentiation mediated by β-catenin contributes to CSC-initiated HCC tumor growth in vivo.

Autistic children often exhibit atypical brain lateralization of language processing, but it is unclear what aspects of language contribute to this phenomenon. This study employed functional near-infrared spectroscopy to measure hemispheric lateralization by estimating hemodynamic responses associated with processing linguistic and non-linguistic auditory stimuli. The study involved a group of autistic children ( N  = 20, mean age = 5.8 years) and a comparison group of nonautistic peers ( N  = 20, mean age = 6.5 years). The children were presented with stimuli with systematically decreasing linguistic relevance: naturalistic native speech, meaningless native speech with scrambled word order, nonnative speech, and music. The results revealed that both groups showed left lateralization in the temporal lobe when listening to naturalistic native speech. However, the distinction emerged between autism and nonautistic in terms of processing the linguistic hierarchy. Specifically, the nonautistic comparison group demonstrated a systematic reduction in left lateralization as linguistic relevance decreased. In contrast, the autism group displayed no such pattern and showed no lateralization when listening to scrambled native speech accompanied by enhanced response in the right hemisphere. These results provide evidence of atypical neural specialization for spoken language in preschool- and school-age autistic children and shed new light on the underlying linguistic correlates contributing to such atypicality at the sublexical level.

This study aimed to develop and evaluate [ 64 Cu]Cu-PSMA-Q as a novel positron emission tomography (PET) imaging agent for prostate cancer detection, assessing its diagnostic accuracy and clinical applicability in comparison to [ 18 F]FDG PET imaging. [ 64 Cu]Cu-PSMA-Q was synthesized, purified, and subjected to comprehensive quality control. Its binding affinity, cellular uptake, and internalization were assessed in vitro using prostate-specific membrane antigen (PSMA)-positive LNCaP C4-2B cells. In vivo toxicity studies were conducted in 12 mouse models (6 per group). Small-animal PET/CT (positron emission tomography/computed tomography) imaging and biodistribution studies were performed on tumor-bearing mice. Clinical evaluation involved PET/CT imaging with [ 64 Cu]Cu-PSMA-Q in 29 prostate cancer patients, with comparative analysis against [ 18 F]FDG PET/CT imaging. Radiation dosimetry was calculated using OLINDA/EXM software, and diagnostic performance metrics, including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and tumor-to-background ratio, were analyzed using SPSS v24.0, with P  < 0.05 considered statistically significant. Comparative analyses utilized t-tests or Mann–Whitney U tests as appropriate. [ 64 Cu]Cu-PSMA-Q achieved over 99% radiochemical purity and a specific activity of 20.5  ±  1 GBq/μmol. In vitro studies demonstrated a dissociation constant (Kd) of 4.083 nM, along with high cellular uptake and internalization in LNCaP C4-2B cells. No significant toxicity was observed in mouse models. Small -animal PET/CT imaging revealed peak tumor uptake at 4 h post-injection in LNCaP C4-2B tumor xenografts. In clinical evaluations, [ 64 Cu]Cu-PSMA-Q PET/CT detected more lesions than [ 18 F]FDG, with significantly higher SUVmax, SUVmean, and tumor-to-background ratios. The mean effective radiation dose was calculated as 4.48 ± 0.99 mSv. [ 64 Cu]Cu-PSMA-Q PET/CT demonstrated superior lesion detection and higher tumor-to-background ratios compared to [ 18 F]FDG PET/CT for prostate cancer visualization. Its advantageous properties, including a favorable half-life, excellent safety profile, and enhanced diagnostic accuracy, support its potential for broad clinical adoption. This study establishes a foundation for further validation of [ 64 Cu]Cu-PSMA-Q in prostate cancer management.

Biochar is considered as a universal conditioner to improve soil quality, but its effects of different addition rates on soil properties, bacterial community structure and plant growth are still unclear, particularly in the typical acid purple soil in the southwest of China. In this study, 110 days of rape growth pot experiment under the application rate of 0.0% rice husk biochar (CK), 0.8% (CT1), 2.0% (CT2) and 4.0% (CT3) to the acid purple soil. Results showed that all biochar additions improved soil pH, soil organic carbon (SOC), total phosphorus, available phosphorus, available potassium concentrations in the acid purple soil. The activity of both invertase and catalase, not urease, was significantly increased with the increasing of biochar addition rates. The 16s-gene sequencing results showed that the Chao1 index was increased only under CT3, and the Shannon index was increased after all biochar applications. Furthermore, biochar increased the relative abundance of bacteria that play important roles in soil carbon and nitrogen cycles, SOC decomposition, plant diseases control and growth. The plant height and biomass production of rapes were increased under the low biochar level (CT1), but not under the higher rates of CT2 and CT3. These results demonstrated that biochar, as a soil conditioner to the acid purple soil, could increase soil pH value, SOC, available phosphorus and potassium and affect carbon and nitrogen cycles related to bacterial communities for promoting plant performance under low application rate.

Conformational cooperativity is a universal molecular effect mechanism and plays a critical role in signaling pathways. However, it remains a challenge to develop artificial molecular networks regulated by conformational cooperativity, due to the difficulties in programming and controlling multiple structural interactions. Herein, we develop a cooperative strategy by programming multiple conformational signals, rather than chemical signals, to regulate protein-oligonucleotide signal transduction, taking advantage of the programmability of allosteric DNA constructs. We generate a cooperative regulation mechanism, by which increasing the loop lengths at two different structural modules induced the opposite effects manifesting as down- and up-regulation. We implement allosteric logic operations by using two different proteins. Further, in cell culture we demonstrate the feasibility of this strategy to cooperatively regulate gene expression of PLK1 to inhibit tumor cell proliferation, responding to orthogonal protein-signal stimulation. This programmable conformational cooperativity paradigm has potential applications in the related fields. Conformational cooperativity is a universal molecular effect mechanism and plays a critical role in signalling pathways. Here the authors present a programmable conformational cooperativity strategy to construct the oligo-protein signal transduction platform for logic operations and gene regulations which can be cooperatively regulated by conformational signals.

Due to strong photoluminescence, extraordinary photostability, excellent biocompatibility, and good water-solubility, metal nanoclusters have attracted enormous attention since discovered. They are found to be novel fluorescence labels for biological applications and environmental monitoring. Recently the chemiluminescence （CL） or electrochemiluminescence （ECL） of metal nanoclusters has received increasing attention. This review covers recent vibrant developments in this field of the past 5 years, and highlights different functions of metal nanoclusters in various CL and ECL systems, such as luminophores, catalysts, and quenchers. Latest synthetic methods of metal nanoclusters used in CL or ECL are also summarized. Furthermore, we discuss some perspectives and critical challenges of this field in the near future.