Identification of KRAS G12V associated clonal neoantigens and immune microenvironment in long-term survival of pancreatic adenocarcinoma.

OBJECTIVE: To investigate the molecular characteristics in tumor immune microenvironment that affect long-term survival of patients with pancreatic adenocarcinoma (PAAD). METHODS: The tumor related genetic features of a female PAAD patient (over 13-year survival) who suffered from multiple recurrences and metastases, and six operations over one decade were investigated deeply. Genomic features and immune microenvironment signatures of her primary lesion as well as six metastatic tumors at different time-points were characterized. RESULTS: High-frequency clonal neoantigenic mutations identified in these specimens revealed the significant associations between clonal neoantigens with her prognosis after each surgery. Meanwhile, the TCGA and ICGC databases were employed to analyse the function of KRAS G12V in pancreatic cancer. CONCLUSIONS: The genomic analysis of clonal neoantigens combined with tumor immune microenvironment could promote the understandings of personalized prognostic evaluation and the stratification of resected PAAD individuals with better outcome.

The synthesis of Cu nanoclusters and their dual mode colorimetric and fluorescent sensing for 2,4-dinitrophenol.

Herein, we have reported a facile one-pot strategy to synthesize fluorescent Cu nanclusters (Cu NCs) by using ʟ-histidine as stabilizer, and ascorbic acid as reducing agent. Cu NCs are stable, water-dispersible, and emit bright cyan emission with a quantum yield 26.08%. The Cu NCs can be employed as colorimetric and fluorimetric dual-mode detector, exhibiting excellent selectivity and sensitivity for detecting 2,4-dinitrophenol (DNP) specifically. Notably, Cu NCs were a sensitive sensor, which had speciality to detect DNP in range of linearity from 0.01 to 0.15 mM with a discernable limit as low as 3.96µM. The mechanism of efficiently selective detection of DNP by Cu NCs was analyzed by UV absorption, fluorescence decay spectrum, and the performance of 'turn off' towards DNP was determined as the inner filter effect and static quenching effect. Further, the environmental tolerance of the Cu NCs probe was estimated by using the different natural water samples, demonstrating its great promise in the field of DNP monitoring and water sample analysis.

A peptide-based pH-sensitive antibacterial hydrogel for healing drug-resistant biofilm-infected diabetic wounds.

Diabetic foot ulcers are a significant complication affecting roughly 15% of diabetic patients. These chronic wounds can be incredibly burdensome, leading to high treatment costs, potential amputations, and additional health complications. Microbiological studies reveal that bacterial infections are the primary culprit behind delayed wound healing. To solve the problem of infection at the wound site, the most fundamental thing is to kill the pathogenic bacteria. Herein, a neoteric strategy to construct novel antibacterial hydrogel COA-T3 that combined photosensitizers (PSs) and antimicrobial peptides (AMPs) via covalent coupling was proposed. Hydrogel COA-T3 composed of quaternized chitosan (QCS) and oxidized dextran (OD) was constructed for co-delivery of the photosensitizer TPI-PN and the antimicrobial peptide HHC10. In vitro and in vivo experiments demonstrated remarkable effectiveness of COA-T3 against drug-resistant bacteria. Furthermore, the hydrogel significantly promoted healing of diabetic infected wounds. This enhanced antibacterial activity is attributed to the pH-sensitive release of both PSs and AMPs within the hydrogel. Additionally, COA-T3 exhibits excellent biocompatibility, making it a promising candidate for wound dressing materials. These findings indicated that the COA-T3 hydrogel is a promising wound dressing material for promoting the healing of diabetic foot ulcers by providing an environment conducive to improved wound healing in diabetic patients.

Dual-mode fluorimetric and colorimetric sensors based on iron and nitrogen co-doped carbon dots for the detection of dopamine.

Determination of dopamine (DA) is crucial for its intimate relationship with clinical trials and biological environment. Herein, Fe, N co-doped carbon dots (AFC-CDs) were fabricated by optimizing precursors and reaction conditions for fluorimetric/colorimetric dual-mode sensing of DA. With synergistic influence of Förster resonance energy transfer and static quenching effect, DA significantly quenched the blue luminescence of AFC-CDs at 442 nm, the production of recognizable tan-brown complex caused evident colorimetric response, achieved the dual-mode fluorimetric/colorimetric sensing for DA. The excellent selectivity and satisfied sensitivity can be confirmed with the limit of detection at 0.29 µM and 2.31 µM via fluorimetric/colorimetric mode respectively. The reliability and practicability were proved by recovery of 94.81-101.61% in real samples. Notably, the proposed electron transfer way between AFC-CDs and DA was hypothesized logically, indicated dual-mode probe provided a promising platform for the sensing of trace DA, and could be expanded in environment and food safety.

Engineering Versatile Bacteria-Derived Outer Membrane Vesicles: An Adaptable Platform for Advancing Cancer Immunotherapy.

In recent years, cancer immunotherapy has undergone a transformative shift toward personalized and targeted therapeutic strategies. Bacteria-derived outer membrane vesicles (OMVs) have emerged as a promising and adaptable platform for cancer immunotherapy due to their unique properties, including natural immunogenicity and the ability to be engineered for specific therapeutic purposes. In this review, a comprehensive overview is provided of state-of-the-art techniques and methodologies employed in the engineering of versatile OMVs for cancer immunotherapy. Beginning by exploring the biogenesis and composition of OMVs, unveiling their intrinsic immunogenic properties for therapeutic appeal. Subsequently, innovative approaches employed to engineer OMVs are delved into, ranging from the genetic engineering of parent bacteria to the incorporation of functional molecules. The importance of rational design strategies is highlighted to enhance the immunogenicity and specificity of OMVs, allowing tailoring for diverse cancer types. Furthermore, insights into clinical studies and potential challenges utilizing OMVs as cancer vaccines or adjuvants are also provided, offering a comprehensive assessment of the current landscape and future prospects. Overall, this review provides valuable insights for researchers involved in the rapidly evolving field of cancer immunotherapy, offering a roadmap for harnessing the full potential of OMVs as a versatile and adaptable platform for cancer treatment.

Controllable synthesis of bifunctional magnetic carbon dots for rapid fluorescent detection and reversible removal of Hg2.

Mercury is one of the most toxic heavy metals, whose identification and separation are crucial for environmental remediation. Till now, it remains a significant challenge upon simultaneous detection and removal of Hg2+. Herein, bifunctional probe magnetic carbon dots were synthesized and optimized via systematic structure manipulation of the carbon and iron precursors towards fluorescence, Hg2+ adsorption and magnetic separation. The probe exhibited blue emission at 440 nm with high quantum yield of 55 % and a high paramagnetism with the saturation magnetization value of 22.70 emu/g. Furthermore, the fluorescent detection of Hg2+ with limit of 5.40 nM and high selectivity were achieved through surface structure manipulation with moderate -NH2, -SH and Fe contents. As a result, the magnetic removal of Hg2+ was consecutively effectuated with high removal efficiency of 98.30 %. The detection and recovery of Hg2+ in real samples were further verified and demonstrated the excellent environmental tolerance of probe. The reusability was viable with recycling at least three turns by external magnet. This work not only provides a promising approach for simultaneous detection and removal of heavy metal pollution, but also provides an excellent example as a versatile platform for multifunction integration via the structure manipulation for other applications.

The synthesis of gold nanoclusters with high stability and their application in fluorometric detection for Hg2+ and cell imaging.

Sensing Hg2+ is significant to protecting human health and environmental ecosystems, for its toxicity and genotoxicity. Here, highly stable fluorescent folic acid (FA)-protected Au nanoclusters (FA-AuNCs) were synthesized by optimizing the reactive parameters with high quantum yield of 34.7%. Main components of Au4L were confirmed by MALDI-TOF, and the electron-rich residues of FA shell enabled FA-AuNCs excellent photostability. FA-AuNCs exhibited sensitive response behavior to Hg2+ with a minimum detectability of 1.3 nM, and presented extreme effect to the detection of Hg2+ in real water. Notably, the cellular imaging and in-situ detection of Hg2+ in cells can be achieved visually. The high selectivity was attributed to the chemical bond formed between Au+ (4f145d10) and Hg2+ (4f145d10). And the internal filter effect and static quenching effect were proved triggering the quenching of FA-AuNCs. The ultra-stable FA-AuNCs provide a potential promising opportunity for the in-situ tracing Hg2+ from environmental and biological samples.

Portable smartphone-integrated AuAg nanoclusters electrospun membranes for multivariate fluorescent sensing of Hg2+, Cu2+ and l-histidine in water and food samples.

Detection of heavy metals have been pivotal due to their non-biodegradability and food chain accumulation. Herein, a multivariate ratiometric sensor was developed by in situ integrating AuAg nanoclusters (NCs) into electrospun cellulose acetate nanofibrous membranes (AuAg-ENM) for visual detection of Hg2+, Cu2+ and consecutive sensing of l-histidine (His), which was integrated into a smartphone platform for quantitative on-site detection. AuAg-ENM achieved multivariate detection of Hg2+ and Cu2+ by fluorescence quenching, and subsequent selective recovery of the Cu2+-quenched fluorescence by His, which distinguished Hg2+ and Cu2+ and fulfilled determination of His simultaneously. Notably, AuAg-ENM achieved selective monitoring of Hg2+, Cu2+ and His in water, food and serum samples with high accuracy comparable to ICP and HPLC tests. A logic gate circuit was devised to further explain and promote the application of AuAg-ENM detection by smartphone App. This portable AuAg-ENM provides a promising reference for fabricating intelligent visual sensors for multiple detection.

Mechanisms of Short-Chain Fatty Acids Derived from Gut Microbiota in Alzheimer's Disease.

Short-chain fatty acids (SCFAs) are important metabolites derived from the gut microbiota through fermentation of dietary fiber. SCFAs participate a number of physiological and pathological processes in the human body, such as host metabolism, immune regulation, appetite regulation. Recent studies on gut-brain interaction have shown that SCFAs are important mediators of gut-brain interactions and are involved in the occurrence and development of many neurodegenerative diseases, including Alzheimer's disease. This review summarizes the current research on the potential roles and mechanisms of SCFAs in AD. First, we introduce the metabolic distribution, specific receptors and signaling pathways of SCFAs in human body. The concentration levels of SCFAs in AD patient/animal models are then summarized. In addition, we illustrate the effects and mechanisms of SCFAs on the cognitive level, pathological features (Aß and tau) and neuroinflammation in AD. Finally, we analyze the translational value of SCFAs as potential therapeutic targets for the treatment of AD.

Preparation of fluorescent bimetallic silver/copper nanoparticles and their utility of dual-mode fluorimetric and colorimetric probe for Hg2.

A dual-mode colorimetric and fluorimetric probe was successfully established based on silver/copper bimetallic nanoparticles (AgCu-BNPs). The AgCu-BNPs were confirmed as individually bimetallic nanoparticles with a mean size of 7.7 ± 0.2 nm, as characterized by high resolution transmission electron microscopy. Intriguingly, the AgCu-BNPs possess both surface plasmon resonances (SPR) and fluorescence emission. AgCu-BNPs emanate bright blue fluorescence with optical emission centered at 442 nm with high quantum yield of 30.3%, and AgCu-BNPs were attenuated or even quenched by Hg2+ via both static and dynamic quenching, coincidently accompanied by a visible color change, which endow AgCu-BNPs a unique utility as dual-mode colorimetric and fluorimetric probes. The detection limits as low as 89 nM and 9 nM were determined by dual-mode of AgCu-BNPs, respectively. The recovery rates in real samples were found to be 97.3-118.8%, and 89.5-112.7% by colorimetric and fluorescent methods separately, demonstrates the good environmental tolerance of the dual-mode probe.

Carbon dots-magnetic nanocomposites for the detection and removal of Hg2.

The dual functional detection and removal of heavy ion metals by carbon dots has become an urgent matter of concern. Here, a unique fluorescent carbon dot-magnetic nanocomposite (Fe3O4/CDs) was prepared by hydrothermal methods for sensitive detection of Hg2+. The Fe3O4/CDs serve as fluorescent probes with higher selectivity and sensitivity for Hg2+, with the lowest detectable limit of 0.3 nM. Hg2+ statically quenched the blue emission of Fe3O4/CDs, which can be restored in the presence of saturated EDTA solution. The utilization of Fe3O4/CDs was fulfilled by recovering their emission conveniently. The recovery of Hg2+ in Chagan Lake water, tap water and drinks was calculated at 96.5 ~ 108.8%, which demonstrates the feasibility of the Fe3O4/CDs sensing system in natural samples. Notably, the Fe3O4/CDs can drive the effective removal of Hg2+ from samples, which is of outstanding significance as a promising probe in environmental monitoring.