Strictosamide promotes wound healing through activation of the PI3K/AKT pathway.

Nauclea officinalis, as a Chinese medicine in Hainan province, had the effect of treating lower limb ulcers, burn infections. In this paper, we studied the effect of Strictosamide (STR), the main bioactive compound in Nauclea officinals, on wound healing and explored its internal mechanism. Firstly, the wound healing potential of STR was evaluated in a rat model, demonstrating its ability to expedite wound healing, mitigate inflammatory infiltration, and enhance collagen deposition. Additionally, immunofluorescence analysis revealed that STR up-regulated the expression of CD31 and PCNA. Subsequently, target prediction, protein-protein interaction (PPI), gene ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of STR for the potential treatment of wound healing. Furthermore, molecular docking was conducted to predict the binding affinity between STR and its associated targets. Additionally, in vivo and in vitro experiments confirmed that STR could increase the expression of P-PI3K, P-AKT and P-mTOR by activating the PI3K/AKT signaling pathway. In summary, this study provided a new explanation for the mechanism by which STR promotes wound healing through network pharmacology, suggesting that STR may be a new candidate for treating wound.

Predicting Risk of Alzheimer's Diseases and Related Dementias with AI Foundation Model on Electronic Health Records.

Early identification of Alzheimer's disease (AD) and AD-related dementias (ADRD) has high clinical significance, both because of the potential to slow decline through initiating FDA-approved therapies and managing modifiable risk factors, and to help persons living with dementia and their families to plan before cognitive loss makes doing so challenging. However, substantial racial and ethnic disparities in early diagnosis currently lead to additional inequities in care, urging accurate and inclusive risk assessment programs. In this study, we trained an artificial intelligence foundation model to represent the electronic health records (EHR) data with a vast cohort of 1.2 million patients within a large health system. Building upon this foundation EHR model, we developed a predictive Transformer model, named TRADE , capable of identifying risks for AD/ADRD and mild cognitive impairment (MCI), by analyzing the past sequential visit records. Amongst individuals 65 and older, our model was able to generate risk predictions for various future timeframes. On the held-out validation set, our model achieved an area under the receiver operating characteristic (AUROC) of 0.772 (95% CI: 0.770, 0.773) for identifying the AD/ADRD/MCI risks in 1 year, and AUROC of 0.735 (95% CI: 0.734, 0.736) in 5 years. The positive predictive values (PPV) in 5 years among individuals with top 1% and 5% highest estimated risks were 39.2% and 27.8%, respectively. These results demonstrate significant improvements upon the current EHR-based AD/ADRD/MCI risk assessment models, paving the way for better prognosis and management of AD/ADRD/MCI at scale.

Ligand-engineering Cu-based catalysts to accelerate the electrochemical reduction of CO2.

Two typical Cu-based complex catalysts with piperazine (PR) and p-phenylenediamine (pPDA) ligands were designed to elucidate whether the ligands can tailor the reduction behavior of the Cu species and thus modulate their electrochemical CO2 reduction reaction (eCO2RR) activity. Specifically, Cu-PR underwent a significant in situ transformation into Cu nanoparticles enriched with a Cuδ+/Cu0 interface for high eCO2RR activity, compared to Cu-pPDA. This finding reveals the importance of ligand engineering in modulating the eCO2RR performance of Cu-based complexes.

Protocol for automated N-glycan sequencing using mass spectrometry and computer-assisted intelligent fragmentation.

Biological functions of glycans are intimately linked to fine details in branches and linkages, which make structural identification extremely challenging. Here, we present a protocol for automated N-glycan sequencing using multi-stage mass spectrometry (MSn). We describe steps for release/purification and derivation of glycans and procedures for MSn scanning. We then detail "glycan intelligent precursor selection" to computationally guide MSn experiments. The protocol can be used for both discrete individual glycans and isomeric glycan mixtures. For complete details on the use and execution of this protocol, please refer to Sun et al.,1 Huang et al.,2 and Huang et al.3.

Determining Cognitive Workload Using Physiological Measurements: Pupillometry and Heart-Rate Variability.

The adoption of Industry 4.0 technologies in manufacturing systems has accelerated in recent years, with a shift towards understanding operators' well-being and resilience within the context of creating a human-centric manufacturing environment. In addition to measuring physical workload, monitoring operators' cognitive workload is becoming a key element in maintaining a healthy and high-performing working environment in future digitalized manufacturing systems. The current approaches to the measurement of cognitive workload may be inadequate when human operators are faced with a series of new digitalized technologies, where their impact on operators' mental workload and performance needs to be better understood. Therefore, a new method for measuring and determining the cognitive workload is required. Here, we propose a new method for determining cognitive-workload indices in a human-centric environment. The approach provides a method to define and verify the relationships between the factors of task complexity, cognitive workload, operators' level of expertise, and indirectly, the operator performance level in a highly digitalized manufacturing environment. Our strategy is tested in a series of experiments where operators perform assembly tasks on a Wankel Engine block. The physiological signals from heart-rate variability and pupillometry bio-markers of 17 operators were captured and analysed using eye-tracking and electrocardiogram sensors. The experimental results demonstrate statistically significant differences in both cardiac and pupillometry-based cognitive load indices across the four task complexity levels (rest, low, medium, and high). Notably, these developed indices also provide better indications of cognitive load responding to changes in complexity compared to other measures. Additionally, while experts appear to exhibit lower cognitive loads across all complexity levels, further analysis is required to confirm statistically significant differences. In conclusion, the results from both measurement sensors are found to be compatible and in support of the proposed new approach. Our strategy should be useful for designing and optimizing workplace environments based on the cognitive load experienced by operators.

Termination of convulsion seizures by destabilizing and perturbing seizure memory engrams.

Epileptogenesis, arising from alterations in synaptic strength, shares mechanistic and phenotypic parallels with memory formation. However, direct evidence supporting the existence of seizure memory remains scarce. Leveraging a conditioned seizure memory (CSM) paradigm, we found that CSM enabled the environmental cue to trigger seizure repetitively, and activating cue-responding engram cells could generate CSM artificially. Moreover, cue exposure initiated an analogous process of memory reconsolidation driven by mammalian target of rapamycin-brain-derived neurotrophic factor signaling. Pharmacological targeting of the mammalian target of rapamycin pathway within a limited time window reduced seizures in animals and interictal epileptiform discharges in patients with refractory seizures. Our findings reveal a causal link between seizure memory engrams and seizures, which leads us to a deeper understanding of epileptogenesis and points to a promising direction for epilepsy treatment.

Coupling of Slack and NaV1.6 sensitizes Slack to quinidine blockade and guides anti-seizure strategy development.

Quinidine has been used as an anticonvulsant to treat patients with KCNT1-related epilepsy by targeting gain-of-function KCNT1 pathogenic mutant variants. However, the detailed mechanism underlying quinidine's blockade against KCNT1 (Slack) remains elusive. Here, we report a functional and physical coupling of the voltage-gated sodium channel NaV1.6 and Slack. NaV1.6 binds to and highly sensitizes Slack to quinidine blockade. Homozygous knockout of NaV1.6 reduces the sensitivity of native sodium-activated potassium currents to quinidine blockade. NaV1.6-mediated sensitization requires the involvement of NaV1.6's N- and C-termini binding to Slack's C-terminus and is enhanced by transient sodium influx through NaV1.6. Moreover, disrupting the Slack-NaV1.6 interaction by viral expression of Slack's C-terminus can protect against SlackG269S-induced seizures in mice. These insights about a Slack-NaV1.6 complex challenge the traditional view of 'Slack as an isolated target' for anti-epileptic drug discovery efforts and can guide the development of innovative therapeutic strategies for KCNT1-related epilepsy.

Isolation of Double-Stranded RNAs by Lithium Chloride Fractionation.

This procedure provides a comprehensive method for isolating double-stranded RNA (dsRNA) that relies on the different solubility of various nucleic acids in lithium chloride (LiC1). The approach offers several notable advantages including simplicity, avoidance of enzymatic treatments, and the ability to obtain relatively high yields of undegraded dsRNA over other conventional techniques. Moreover, it allows for the separation of different groups of cellular and viral nucleic acids from a single tissue sample. This method was further improved to increase the purity of dsRNA using plant tissues infected by RNA viruses.

Polyoxometalate Li3 PW12 O40 and Li3 PMo12 O40 Electrolytes for High-energy All-solid-state Lithium Batteries.

Solid-state lithium (Li) batteries promise both high energy density and safety while existing solid-state electrolytes (SSEs) fail to satisfy the rigorous requirements of battery operations. Herein, novel polyoxometalate SSEs, Li3 PW12 O40 and Li3 PMo12 O40 , are synthesized, which exhibit excellent interfacial compatibility with electrodes and chemical stability, overcoming the limitations of conventional SSEs. A high ionic conductivity of 0.89 mS cm-1 and a low activation energy of 0.23 eV are obtained due to the optimized three-dimensional Li+ migration network of Li3 PW12 O40 . Li3 PW12 O40 exhibits a wide window of electrochemical stability that can both accommodate the Li anode and high-voltage cathodes. As a result, all-solid-state Li metal batteries fabricated with Li/Li3 PW12 O40 /LiNi0.5 Co0.2 Mn0.3 O2 display a stable cycling up to 100 cycles with a cutoff voltage of 4.35 V and an areal capacity of more than 4 mAh cm-2 , as well as a cost-competitive SSEs price of $5.68 kg-1 . Moreover, Li3 PMo12 O40 homologous to Li3 PW12 O40 was obtained via isomorphous substitution, which formed a low-resistance interface with Li3 PW12 O40 . Applications of Li3 PW12 O40 and Li3 PMo12 O40 in Li-air batteries further demonstrate that long cycle life (650 cycles) can be achieved. This strategy provides a facile, low-cost strategy to construct efficient and scalable solid polyoxometalate electrolytes for high-energy solid-state Li metal batteries.

ADCdb: the database of antibody-drug conjugates.

Antibody-drug conjugates (ADCs) are a class of innovative biopharmaceutical drugs, which, via their antibody (mAb) component, deliver and release their potent warhead (a.k.a. payload) at the disease site, thereby simultaneously improving the efficacy of delivered therapy and reducing its off-target toxicity. To design ADCs of promising efficacy, it is crucial to have the critical data of pharma-information and biological activities for each ADC. However, no such database has been constructed yet. In this study, a database named ADCdb focusing on providing ADC information (especially its pharma-information and biological activities) from multiple perspectives was thus developed. Particularly, a total of 6572 ADCs (359 approved by FDA or in clinical trial pipeline, 501 in preclinical test, 819 with in-vivo testing data, 1868 with cell line/target testing data, 3025 without in-vivo/cell line/target testing data) together with their explicit pharma-information was collected and provided. Moreover, a total of 9171 literature-reported activities were discovered, which were identified from diverse clinical trial pipelines, model organisms, patient/cell-derived xenograft models, etc. Due to the significance of ADCs and their relevant data, this new database was expected to attract broad interests from diverse research fields of current biopharmaceutical drug discovery. The ADCdb is now publicly accessible at: https://idrblab.org/adcdb/.

Autophagy-mediated NKG2D internalization impairs NK cell function and exacerbates radiation pneumonitis.

Introduction: Radiation pneumonitis is a critical complication that constrains the use of radiation therapy for thoracic malignancies, leading to substantial morbidity via respiratory distress and lung function impairment. The role of Natural killer (NK) cells in inflammatory diseases is well-documented; however, their involvement in radiation pneumonitis is not fully understood. Methods: To explore the involvement of NK cells in radiation pneumonitis, we analyzed tissue samples for NK cell presence and function. The study utilized immunofluorescence staining, western blotting, and immunoprecipitation to investigate CXCL10 and ROS levels, autophagy activity, and NKG2D receptor dynamics in NK cells derived from patients and animal models subjected to radiation. Result: In this study, we observed an augmented infiltration of NK cells in tissues affected by radiation pneumonitis, although their function was markedly diminished. In animal models, enhancing NK cell activity appeared to decelerate the disease progression. Concomitant with the disease course, there was a notable upsurge in CXCL10 and ROS levels. CXCL10 was found to facilitate NK cell migration through CXCR3 receptor activation. Furthermore, evidence of excessive autophagy in patient NK cells was linked to ROS accumulation, as indicated by immunofluorescence and Western blot analyses. The association between the NKG2D receptor and its adaptor proteins (AP2 subunits AP2A1 and AP2M1), LC3, and lysosomes was intensified after radiation exposure, as demonstrated by immunoprecipitation. This interaction led to NKG2D receptor endocytosis and subsequent lysosomal degradation. Conclusion: Our findings delineate a mechanism by which radiation-induced lung injury may suppress NK cell function through an autophagy-dependent pathway. The dysregulation observed suggests potential therapeutic targets; hence, modulating autophagy and enhancing NK cell activity could represent novel strategies for mitigating radiation pneumonitis.

Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome.

Obesity is a metabolic disorder characterized by the hypertrophy expansion of adipose tissue, resulting in dysregulated energy metabolism, and accompanied by chronic low-grade inflammation. Adipose tissue macrophages (ATMs), a principal component of inflammation, respond to microenvironment signals and modulate adipose tissue remodeling and metabolic processes situation-specific. However, the mechanisms governing how the organism maintains equilibrium between its chronic inflammation and metabolism still need to be understood. Here, we describe a novel role of apolipoprotein E (ApoE), which associated with lipid particles, in maintaining fat deposition and system metabolic inflammation. Using human samples and mouse models, we show that ApoE is robustly downregulated in obese individuals, db/db mice, and mice of high-fat diet (HFD) feeding and increased in obese subjects with diabetes. Furthermore, we found that ApoE deficiency mice globally prevented obesity by restraining adipose tissue expansion and improved systemic glucose tolerance and insulin sensitivity. However, macrophage contributed to metabolic inflammation due to increased IL-1ß production in adipose tissue from ApoE-/- mice induced by HFD. Our results suggest that the role of ApoE in regulating obesity and obesity-associated glucose dysregulation is inconsistent. Mechanistically, ApoE modulates of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome priming and activation step. Thus, our studies might provide new sights into ApoE, which is required for obesity-induced hyperglycemia, hyperinsulinism, and adaptive inflammation responses but diminishes the tolerance towards a subsequent metabolic inflammatory challenge. Our study shed new light on the integral role of apolipoprotein APOE in immunometabolism and adipose tissue homeostasis.

Identification of ACBD3 as a new molecular biomarker in pan-cancers through bioinformatic analysis: a preclinical study.

BACKGROUND: Acyl-CoA-binding domain-containing 3 (ACBD3) is a multifunctional protein, that plays essential roles in cellular signaling and membrane domain organization. Although the precise roles of ACBD3 in various cancers remain unclear. Thus, we aimed to determine the diverse roles of ACBD3 in pan-cancers. METHODS: Relevant clinical and RNA-sequencing data for normal tissues and 33 tumors from The Cancer Genome Atlas (TCGA) database, the Human Protein Atlas, and other databases were applied to investigate ACBD3 expression in various cancers. ACBD3-binding and ACBD3-related target genes were obtained from the STRING and GEPIA2 databases. The possible functions of ACBD3-binding genes were explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We also applied the diagnostic value and survival prognosis analysis of ACBD3 in pan-cancers using R language. The mutational features of ACBD3 in various TCGA cancers were obtained from the cBioPortal database. RESULTS: When compared with normal tissues, ACBD3 expression was statistically upregulated in eleven cancers and downregulated in three cancers. ACBD3 expression was remarkably different among various pathological stages of tumors, immune and molecular subtypes of cancers, cancer phosphorylation levels, and immune cell infiltration. The survival of four tumors was correlated with the expression level of ACBD3, including pancreatic adenocarcinoma, adrenocortical carcinoma, sarcoma, and glioma. The high accuracy in diagnosing multiple tumors and its correlation with prognosis indicated that ACBD3 may be a potential biomarker of pan-cancers. CONCLUSION: According to our pan-cancer analysis, ACBD3 may serve as a remarkable prognostic and diagnostic biomarker of pan-cancers as well as contribute to tumor development. ACBD3 may also provide new directions for cancer treatment targets in the future.

Gender authorship trends of gastric cancer in the top journals of gastroenterology: A 20-year perspective.

Gender authorship trends have been explored in varied medical specialties, and no study had observed in the field of gastric cancer. Therefore, we aimed to access whether the "gender gap" in authorship existed in gastric cancer in the leading gastroenterological journals over the last 2 decades. All original articles published from 2000 to 2020 in 9 leading gastroenterological journals were collected. Information on the first and senior author's gender, country of author's institution, and impact factor of journals were collected. Chi-square tests and multivariable logistic regression were used for data analysis. A total of 5785 original articles were included and analyzed, of which 440 (7.61%) were articles on gastric cancer and 5345 (92.39%) covered other topics. Fewer female authors published original articles as first (19.32%, 85/440) and senior authors (14.32%, 63/440) compared with males. Remarkably, a significant increase in female authorship was discovered. The proportion of female first authors grown from 12.99% to 30.89% during the last 20 years (P < .001), but not in senior authors (P = .175). Multivariable logistic analysis showed that female first authors demonstrated a higher percentage when senior authors were female (odds ratio, 2.040; 95% confidence interval, 1.105-3.769). Although a statistically ascending tendency in female first authors on gastric cancer has been going on over the last 20 years, the exorbitant gender gap still exists. This gap may help explain the continued underrepresentation of women within both clinical work and academic research, and prompt us to look further for the underlying causes.

A Study on the C, N, and P Contents and Stoichiometric Characteristics of Forage Leaves Based on Fertilizer-Reconstructed Soil in an Alpine Mining Area.

In this study, we analyzed the C, N, and P contents and stoichiometric characteristics of forage leaves of five species (Elymus breviaristatus cv. Tongde, Poa crymophila cv. Qinghai, Puccinellia tenuiflora cv. Qinghai, Festuca sinensis cv. Qinghai, and Poa pratensis cv. Qinghai) in "fertilizer-reconstructed soil" through integrative soil amendment with parched sheep manure and granular organic fertilizer in an alpine mining area. A model is fitted in order to screen out the best forage species suitable for vegetation restoration in the alpine mining area and the most favorable fertilizer dosage to improve the nutrient content of forage leaves. The results showed that (1) increasing the dosages of granular organic fertilizer and sheep manure had little effect on the C content of the five types of forage grasses, but they could significantly increase the N and P contents and N/P of the manually restored grassland in the alpine mining area (p < 0.05). (2) The productivity and stability of the five species were ranked as follows: Elymus breviaristatus cv. Tongde > Puccinellia tenuiflora cv. Qinghai > Festuca sinensis cv. Qinghai > Poa pratensis cv. Qinghai > Poa crymophila cv. Qinghai. (3) According to the fitted least squares model and the willingness to maximize the C, N, and P contents of the leaves, the ranking of the five forage grasses was described by the Prediction Profiler as follows: Elymus breviaristatus cv. Tongde > Puccinellia tenuiflora cv. Qinghai > Festuca sinensis cv. Qinghai > Poa crymophila cv. Qinghai > Poa pratensis cv. Qinghai. (4) The predictive model suggested that the optimal contents of C, N, and P in Elymus breviaristatus cv. Tongde, Festuca sinensis cv. Qinghai, and Poa pratensis cv. Qinghai leaves could be achieved with the application of 3.6 kg/m2 of granular organic fertilizer and 45.0 kg/m2 of sheep manure. For Poa crymophila cv. Qinghai leaves, the ideal content was attained by applying 0 kg/m2 of granular organic fertilizer and 45.0 kg/m2 of sheep manure. Lastly, the optimal C, N, and P contents in Puccinellia tenuiflora cv. Qinghai leaves could be obtained through the application of 3.6 kg/m2 of granular organic fertilizer combined with 0 kg/m2 of sheep manure. In conclusion, the study's results highlight the significant practical value of the fertilizer-reconstructed soil for vegetation restoration in alpine mining regions.

Trends in gender disparity in the field of Helicobacter pylori research from 2000 to 2020: A cross-sectional study.

Many studies have investigated gender disparity in scientific publications, but this has been poorly studied in the field of digestive diseases. This study aimed to determine the gender difference of first and senior authors in publications related to Helicobacter pylori (H. pylori) during the past 20 years. Data were derived from original articles published in the main journals of digestive diseases (Journal of Hepatology, Gut, Gastroenterology, American Journal of Gastroenterology, Endoscopy, Gastrointestinal Endoscopy, Alimentary Pharmacology and Therapeutics, Digestive Endoscopy, Journal of Gastroenterology, Helicobacter, and Gastric Cancer) in 2000, 2005, 2010, 2015, and 2020. These original articles were classified according to the gender and nationality of the first and senior (last listed) authors. Linear-by-linear association test was used to analyze the proportion of women authors over time. Multivariable logistic regression was applied to explain the factors impacting authorship difference of first and senior authors. A total of 561 original articles on H. pylori were collected for this study, accounting for 10.70% in 2000 to 7.60% in 2020 among all articles. In these original articles, the percentage of women first authors increased from 14.60% in 2000 to 45.0% in 2020 (P < .001). The percentage of women senior authors increased from 5.60% in 2000 to 18.80% in 2020 (P < .001). Women first authors were more likely to perform research with women senior authors (18.42%) than with men senior authors (10.23%, P < .001). The proportion of women first authors from Oceania were higher than that from North and South America (P = .004), whereas there was no statistical difference regarding women senior authors. In the past 2 decades, although the percentage of women authors among both first and senior authors in the field of H. pylori research has increased significantly, women are still a minority in original research.

NAT10-dependent N4-acetylcytidine modification mediates PAN RNA stability, KSHV reactivation, and IFI16-related inflammasome activation.

N-acetyltransferase 10 (NAT10) is an N4-acetylcytidine (ac4C) writer that catalyzes RNA acetylation at cytidine N4 position on tRNAs, rRNAs and mRNAs. Recently, NAT10 and the associated ac4C have been reported to increase the stability of HIV-1 transcripts. Here, we show that NAT10 catalyzes ac4C addition to the polyadenylated nuclear RNA (PAN), a long non-coding RNA encoded by the oncogenic DNA virus Kaposi's sarcoma-associated herpesvirus (KSHV), triggering viral lytic reactivation from latency. Mutagenesis of ac4C sites in PAN RNA in the context of KSHV infection abolishes PAN ac4C modifications, downregulates the expression of viral lytic genes and reduces virion production. NAT10 knockdown or mutagenesis erases ac4C modifications of PAN RNA and increases its instability, and prevents KSHV reactivation. Furthermore, PAN ac4C modification promotes NAT10 recruitment of IFN-γ-inducible protein-16 (IFI16) mRNA, resulting in its ac4C acetylation, mRNA stability and translation, and eventual inflammasome activation. These results reveal a novel mechanism of viral and host ac4C modifications and the associated complexes as a critical switch of KSHV replication and antiviral immunity.

Network pharmacology and experimental validation of Maxing Shigan decoction in the treatment of influenza virus-induced ferroptosis.

Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide. Influenza A virus (IAV) has been found to activate multiple programmed cell death pathways, including ferroptosis. Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. However, little is known about how influenza viruses induce ferroptosis in the host cells. In this study, based on network pharmacology, we predicted the mechanism of action of Maxing Shigan decoction (MXSGD) in IAV-induced ferroptosis, and found that this process was related to biological processes, cellular components, molecular function and multiple signaling pathways, where the hypoxia inducible factor-1(HIF-1) signaling pathway plays a significant role. Subsequently, we constructed the mouse lung epithelial (MLE-12) cell model by IAV-infected in vitro cell experiments, and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage, increased reactive oxygen species (ROS) release, increased total iron and iron ion contents, decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4 (GPX4), increased expression of acyl-CoA synthetase long chain family member 4 (ACSL4), and enhanced activation of hypoxia inducible factor-1α (HIF-1α), induced nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in the HIF-1 signaling pathway. Treatment with MXSGD effectively reduced intracellular viral load, while reducing ROS, total iron and ferrous ion contents, repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway. Finally, based on animal experiments, it was found that MXSGD effectively alleviated pulmonary congestion, edema and inflammation in IAV-infected mice, and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.

A dual-cycle amplification-based electrochemical platform for sensitive detection of tobramycin.

BACKGROUND: Tobramycin (TOB), an essential aminoglycoside antibiotic in human life, poses potential threats due to its residues in the environment. The primary concern is the adverse impact of excessive TOB on human kidneys, hearing, and other organs, significantly affecting human health. Constructing a sensitive electrochemical platform for simple and rapid trace detection is crucial. Herein, to enhance the sensitivity of TOB detection in the environment and mitigate the risks associated with residual antibiotics, an ultrasensitive electrochemical aptasensor was developed. RESULTS: The sensor employs a dual-cycle amplification strategy involving catalytic hairpin assembly (CHA) and exonuclease III (Exo III) for efficient signal amplification. Simultaneously, the electrode performance was optimized by incorporating gold nanowires (AuNWs) onto the surface of reduced graphene oxide (PDA-rGO). Specifically, in the presence of TOB, which binds to the aptamer (Apt), dsDNA dissociates, releasing cDNA to open hairpin 1 (HP1) and initiate the CHA cycle with the participation of hairpin 2 (HP2). Exo III shears HP1 in the HP1/HP2 complex, freeing HP2 to participate in the CHA cycle again. Ultimately, a significant amount of signal label is retained on the electrode by hybridizing with sheared HP1, generating a robust electrical signal. SIGNIFICANCE: Through the signal amplification strategy, the aptasensor design provides a broad linear range of 0.005-500 nM, with a low detection limit of 0.112 pM for TOB. It is worth mentioning that the aptasensor displayed favorable stability, specificity, and reproducibility, and has been successfully applied to practical samples, demonstrating its utility in practical applications.