Gut microbiota interactions with antitumor immunity in colorectal cancer: From understanding to application.

Colorectal cancer (CRC) is one of highly prevalent cancer. Immunotherapy with immune checkpoint inhibitors (ICIs) has dramatically changed the landscape of treatment for many advanced cancers, but CRC still exhibits suboptimal response to immunotherapy. The gut microbiota can affect both anti-tumor and pro-tumor immune responses, and further modulate the efficacy of cancer immunotherapy, particularly in the context of therapy with ICIs. Therefore, a deeper understanding of how the gut microbiota modulates immune responses is crucial to improve the outcomes of CRC patients receiving immunotherapy and to overcome resistance in nonresponders. The present review aims to describe the relationship between the gut microbiota, CRC, and antitumor immune responses, with a particular focus on key studies and recent findings on the effect of the gut microbiota on the antitumor immune activity. We also discuss the potential mechanisms by which the gut microbiota influences host antitumor immune responses as well as the prospective role of intestinal flora in CRC treatment. Furthermore, the therapeutic potential and limitations of different modulation strategies for the gut microbiota are also discussed. These insights may facilitate to better comprehend the interplay between the gut microbiota and the antitumor immune responses of CRC patients and provide new research pathways to enhance immunotherapy efficacy and expand the patient population that could be benefited by immunotherapy.

A dual "turn-on" biosensor based on AIE effect and FRET for in situ detection of miR-125b biomarker in early Alzheimer's disease.

MicroRNA-125b (miR-125b) is highly associated with synaptic dysfunction and tau hyperphosphorylation in the early pathogenesis of Alzheimer's disease (AD), making it a promising biomarker for early AD diagnosis. Hence, there is an urgent need for a reliable sensing platform to assist in situ miR-125b detection. In this work, we report a dual "turn-on" fluorescence biosensor based on the nanocomposite of aggregation-induced emission fluorogen (AIEgen)-labeled oligonucleotide (TPET-DNA) probes immobilized on the surface of cationic dextran modified molybdenum disulfide (TPET-DNA@Dex-MoS2). In the presence of the target, TEPT-DNA can hybridize with miR-125b to form a DNA/RNA duplex, causing TPET-DNA to detach from the surface of Dex-MoS2 that simultaneously activates the dual fluorescence enhancement processes: (1) recovery of TPET-DNA signal and (2) strong fluorescent emission from AIEgen triggered by restriction of the intramolecular rotation. The sensing performance of TPET-DNA@Dex-MoS2 was demonstrated by detecting miR-125b in vitro with good sensitivity at the picomolar level and rapid response (≤1 h) without amplification procedures. Furthermore, our nanoprobes exhibited excellent imaging capabilities to aid real-time monitoring of the endogenous miR-125b in PC12 cells and brain tissues of mice AD model induced by local administration of okadaic acid (OA). The fluorescence signals of the nanoprobes indicated miR-125b was spatially associated with phosphorylated tau protein (p-tau) in vitro and in vivo. Therefore, TPET-DNA@Dex-MoS2 could be a promising tool for in situ and real-time monitoring of the AD-related microRNAs and also provide mechanistic insight into the early prognosis of AD.

Research on Educational Robot System Based on Vision Processing.

Aimed at the poor recognition effect of current educational robots on objects with complex shapes and colors and the single design of related experiments, this paper proposes a robot teaching instrument. The robot adopts a servo motor with an encoder, a drive, and a variety of sensors to realize a motor current loop, speed loop, position loop, and closed-loop control functions. Three experimental schemes were designed: a PID adjustment experiment, a robot obstacle avoidance and object-grasping program writing experiment, and a complex object recognition experiment based on cascade classifiers. The robot is conducive to improving students' self-initiative ability, deepening their understanding of PID closed-loop control, multi-sensor fusion, and deep learning knowledge. It can improve students' programming ability, enabling them to effectively combine theory and practice, as well as to comprehensively apply professional knowledge.

Near-Infrared Photothermally Enhanced Photo-Oxygenation for Inhibition of Amyloid-ß Aggregation Based on RVG-Conjugated Porphyrinic Metal-Organic Framework and Indocyanine Green Nanoplatform.

Amyloid aggregation is associated with many neurodegenerative diseases such as Alzheimer's disease (AD). The current technologies using phototherapy for amyloid inhibition are usually photodynamic approaches based on evidence that reactive oxygen species can inhibit Aß aggregation. Herein, we report a novel combinational photothermally assisted photo-oxygenation treatment based on a nano-platform of the brain-targeting peptide RVG conjugated with the 2D porphyrinic PCN-222 metal-organic framework and indocyanine green (PCN-222@ICG@RVG) with enhanced photo-inhibition in Alzheimer's Aß aggregation. A photothermally assisted photo-oxygenation treatment based on PCN@ICG could largely enhance the photo-inhibition effect on Aß42 aggregation and lead to much lower neurotoxicity upon near-infrared (NIR) irradiation at 808 nm compared with a single modality of photo-treatment in both cell-free and in vitro experiments. Generally, local photothermal heat increases the instability of Aß aggregates and keeps Aß in the status of monomers, which facilitates the photo-oxygenation process of generating oxidized Aß monomers with low aggregation capability. In addition, combined with the brain-targeting peptide RVG, the PCN-222@ICG@RVG nanoprobe shows high permeability of the human blood-brain barrier (BBB) on a human brain-on-a-chip platform. The ex vivo study also demonstrates that NIR-activated PCN-222@ICG@RVG could efficiently dissemble Aß plaques. Our work suggests that the combination of photothermal treatment with photo-oxygenation can synergistically enhance the inhibition of Aß aggregation, which may boost NIR-based combinational phototherapy of AD in the future.

Hybrid theranostic microbubbles for ultrasound/photoacoustic imaging guided starvation/low-temperature photothermal/hypoxia-activated synergistic cancer therapy.

Constructing a theranostic agent for high-contrast multimodality imaging-guided synergistic therapy with long-term tumor retention and minimum systemic side effects still remains a major challenge. Herein, a hybrid microbubble-based theranostic platform was developed for dual-modality ultrasound (US) and enhanced photoacoustic (PA) imaging-guided synergistic tumor therapy by combining starvation therapy, low-temperature photothermal therapy (PTT), and hypoxia-activated therapy, based on polydopamine (PDA) doped poly(vinyl alcohol) microbubbles loaded with glucose oxidase (GOx) (PDA-PVAMBs@GOx) and hypoxia-activated prodrug (HAP) tirapazamine (TPZ). For dual-modality US/enhanced PA imaging, PDA-PVAMBs provided 6.5-fold amplified PA signals relative to freely dispersed PDA nanoparticles (PDA NPs). For synergistic cancer therapy, oxygen (O2) carried by PDA-PVAMBs@GOx was first released to promote starvation therapy by loaded GOx. Then, moderate near-infrared (NIR) laser irradiation triggered PTT and improved enzymatic activity of GOx with its optimal activity around 47 °C. Subsequently, GOx-mediated tumor starvation depleted O2 and exacerbated the hypoxia environment, thereby activating the toxicity of TPZ in the tumor site. Through dual-modality US/PA imaging monitoring, PDA-PVAMBs@GOx with long-term retention (∼7 days) combined with PTT and TPZ significantly inhibited the growth of solid tumors with minimum systemic side effects, which might be a powerful tool for effective tumor treatment.

Dual-Depletion of Intratumoral Lactate and ATP with Radicals Generation for Cascade Metabolic-Chemodynamic Therapy.

Increasing evidence has demonstrated that lactate and adenosine triphosphate (ATP) both play important roles in regulating abnormal metabolism in the tumor microenvironment. Herein, an O2 self-supplying catalytic nanoagent, based on tannic acid (TA)-Fe(III) coordination complexes-coated perfluorooctyl bromide (PFOB) nanodroplets with lactate oxidases (LOX) loading (PFOB@TA-Fe(III)-LOX, PTFL), is designed for cascade metabolic-chemodynamic therapy (CDT) by dual-depletion of lactate and ATP with hydroxyl • OH radicals generation. Benefiting from the catalytic property of loaded LOX and O2 self-supplying of PFOB nanodroplets, PTFL nanoparticles (NPs) efficiently deplete tumoral lactate for down-regulation of vascular endothelial growth factor expression and supplement the insufficient endogenous H2 O2 . Simultaneously, TA-Fe(III) complexes release Fe(III) ions and TA in response to intracellular up-regulated ATP in tumor cells followed by TA-mediated Fe(III)/Fe(II) conversion, leading to the depletion of energy source ATP and the generation of cytotoxic • OH radicals from H2 O2 . Moreover, TA-Fe(III) complexes provide photoacoustic contrast as imaging guidance to enhance therapeutic accuracy. As a result, PTFL NPs efficiently accumulate in tumors for suppression of tumor growth and show evidence of anti-angiogenesis and anti-metastasis effects. This multifunctional nanoagent may provide new insight for targeting abnormal tumor metabolism with the combination of CDT to achieve a synergistic therapeutic effect.

Hepatoprotection of Lycii Fructus Polysaccharide against Oxidative Stress in Hepatocytes and Larval Zebrafish.

Scavenging of oxidative stress by antioxidants may provide a therapeutic strategy for nonalcoholic fatty liver disease (NAFLD). Increasing evidence is supporting the potential application of natural resourced polysaccharides as promising prevention or treatment strategies against NAFLD. In the current study, an acidic heteropolysaccharide, LFP-a1, was isolated and purified from Lycii fructus with successively hot water refluxing extraction, alcohol precipitation, protein removal, and DEAE-52 cellulose chromatographic separation. LFP-a1 was a complicated structured polysaccharide with an average MW of 4.74 × 104 Da and composed of 6 monosaccharides and 1 uronic acid. Preexposure of LFP-a1 could increase the cell viability and reverse the abnormal oxidative stress though inhibition of mitochondrial-mediated apoptotic pathway and correction of cell cycle progression against H2O2 hepatoxicity in NAFLD model L02 cells. Consistently, in vivo study in thioacetamide- (TAA-) induced NAFLD model zebrafish larvae showed LFP-a1 preserved the liver integrity and alleviated TAA-induced oxidative stress through downregulation of abnormal apoptosis. These observations indicated the hepatoprotective activity of LFP-a1, which may be applied for the prevention or treatment of NAFLD or other oxidative stress-related diseases.