The understanding of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFK-2/FBPase 3, PFKFB3) has advanced considerably since its initial identification in human macrophages in the mid-1990s. As a vital regulator of glycolysis, accumulating studies have suggested that PFKFB3 is associated with many aspects of cancer, including carcinogenesis, cancer cell proliferation, vessel aggressiveness, drug resistance and tumor microenvironment. In this review, we summarize current knowledge of PFKFB3 regulation by several signal pathways and its function in cancer development in different cell types in cancer tissues. Ubiquitous PFKFB3 has emerged as a potential target for anti-neoplastic therapy.

Metal–inorganic semiconductor–metal photodetectors (MSM‐PDs) have received great attention in many areas, such as optical fiber communication, sensing, missile guidance, etc., due to their inherent merits of high speed, high sensitivity, and easy integration. This review focuses on MSM‐PDs with the semiconductor layer made of inorganic materials including traditional semiconductors (such as GaAs and Si), the third‐generation wide bandgap semiconductors (such as GaN, ZnO, and SiC), as well as several emerging semiconductors (such as perovskites and 2D materials). First, the basic structures of MSM‐PDs, including the planar and vertical configurations, are presented. Then, their working principles of MSM‐PDs are discussed. Subsequently, the research progresses on MSM‐PDs consisting of different photosensitive semiconductor materials are described in detail. Additionally, the efforts to optimize MSM‐PDs from the aspects of dark current, response speed, responsivity, spectral adjustment, etc., are also introduced. Finally, the review is concluded with the perspectives of MSM‐PDs from the authors’ vision.

Purpose: Colitis-associated colorectal cancer (CAC) poses substantial challenges for effective treatment. Currently, there is a considerable need for the development of orally bioavailable dosage forms that enable the safe and effective delivery of therapeutic drugs to local diseased lesions in the gastrointestinal tract.Experimental Design: In this study, we developed orally deliverable nanotherapeutics for the synergistic treatment of inflammatory bowel diseases (IBDs) and CAC. Water-insoluble curcumin (CUR) and 7-ethyl-10-hydroxycamptothecin (SN38), which served as anti-inflammatory and cytotoxic agents, respectively, were chemically engineered into hydrophilic mucoadhesive chitosan for the generation of chitosan-drug amphiphiles.Results: The resulting amphiphilic constructs formed core-shell nanostructures in aqueous solutions and were orally administered for in vivo therapeutic studies. Using a preclinical CAC mouse model, we showed that the orally delivered nanotherapeutics locally accumulated in inflamed intestinal regions and tumor tissues. Furthermore, the therapeutic synergy of the combined nanotherapeutics in CAC mice was evaluated. Compared with their individual drug forms, combined CUR and SN38 nanoparticles yielded synergistic effects to alleviate intestinal inflammation and protect mice from ulcerative colitis. Notably, the combinatorial therapy demonstrated a remarkable tumor shrinkage with only ~6% of the total tumors exceeding 4 mm in diameter, whereas ~35% of tumors were observed to exceed a diameter of 4 mm in the saline-treated CAC mice. These data suggest a new and reliable approach for improving the treatment of IBD and CAC.Conclusions: Our results showed that bioadhesive chitosan materials can be used to produce colloidal-stable nanotherapeutics that are suitable for oral delivery. Both nanotherapeutics exhibited substantial accumulation in inflamed intestinal regions and tumor tissues and showed good synergy for treating CAC, warranting further clinical translation.

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Organic photomultiplication photodetectors have attracted considerable research interest due to their extremely high external quantum efficiency and corresponding high detectivity. Significant progress has been made in the aspects of their structural design and performance improvement in the past few years. There are two types of organic photomultiplication photodetectors, which are made of organic small molecular compounds and polymers. In this paper, the research progress in each type of organic photomultiplication photodetectors based on the trap assisted carrier tunneling effect is reviewed in detail. In addition, other mechanisms for the photomultiplication processes in organic devices are introduced. Finally, the paper is summarized and the prospects of future research into organic photomultiplication photodetectors are discussed.

Galunisertib (Gal) is a transforming growth factor (TGF-β) blockade which is being investigated as a potential tumor immunotherapy candidate drug in clinical trials. However, primary or acquired resistance is often found in the recruited cancer patients, which limits its clinical application. Tumor immune microenvironment can be regulated by intestinal microbiota, leading to different therapeutic outcomes. It is hypothesized that manipulation of cancer patients' intestinal microbiome in the early stage of therapy may be a promising strategy to improve the therapeutic efficacy of Gal. Methods : 4T1 and H22 subcutaneous tumor bearing mice were used to evaluate the therapeutic effect. Escherichia coli strain Nissle 1917 (EcN), a widely used probiotic bacteria, was orally delivered to the tumor bearing mice daily along with Gal treatment. Antitumor effect of the combination therapy was evaluated by tumor volume, histological staining of tumor tissues. Furthermore, flow cytometry was performed to analyze the alteration of immune microenvironment in tumor bed after treatment. The suppressing effect of the combination therapy on tumor invasiveness and metastasis was evaluated in both mice and zebrafish xenografts models. Fecal sample 16S rRNA gene sequencing was conducted to analyze changes of intestinal microbial diversity. The effect of intestinal microbiota on tumor suppression after receiving EcN was further tested by fecal transplant. Results : The therapeutic outcomes in tumor growth inhibition and metastasis suppression of Gal were significantly potentiated by EcN, resulting from the strengthened antitumor immunity. EcN was able to relieve the immunosuppressive tumor microenvironment, which was evidenced by enhanced tumor-specific effector T cells infiltration and dendritic cells activation. Intestinal microbiota was modulated by EcN, illustrated by a shift of gut microbiome toward certain beneficial bacteria. Conclusion : These results suggested that Gal combined with EcN might be a novel therapeutic approach with great potential of clinical implications for cancer prevention or treatment.

BackgroundInterleukin-2 (IL-2) serves as a pioneer of immunotherapeutic agent in cancer treatment. However, there is a considerable proportion of patients who cannot benefit from this therapy due to the limited clinical responses and dose-limiting toxicities. Mounting evidence indicates that commensal microbiota shapes the outcome of cancer immunotherapies. In this study, we aim to investigate the enhancing effect of Akkermansia muciniphila (AKK), a beneficial commensal microbe receiving considerable attentions, on the antitumor efficacy of IL-2 and explore the underlying molecular mechanism.MethodsColorectal carcinoma patient-derived tumor tissues were used to evaluate the therapeutic efficacy of combination treatment. AKK was orally delivered to B16F10 and CT26 tumor-bearing mice along with systemic IL-2 treatment. Flow cytometry was carried out to analyze the tumor immune microenvironment. The molecular mechanism of the enhanced therapeutic efficacy was explored by RNA-seq and then verified in tumor-bearing mice.ResultsCombined treatment with IL-2 and AKK showed a stronger antitumor efficacy in colorectal cancer patient-derived tumor tissues. Meanwhile, the therapeutic outcome of IL-2 was significantly potentiated by oral administration of AKK in subcutaneous melanoma and colorectal tumor-bearing mice, resulting from the strengthened antitumor immune surveillance. Mechanistically, the antitumor immune response elicited by AKK was partially mediated by Amuc, derived from the outer membrane protein of AKK, through activating toll-like receptor 2 (TLR2) signaling pathway. Besides, oral supplementation with AKK protected gut barrier function and maintained mucosal homeostasis under systemic IL-2 treatment.ConclusionThese findings propose that IL-2 combined with AKK is a novel therapeutic strategy with prospecting application for cancer treatment in clinical practice.

Combination therapy using distinct mode-of-action drugs has sparked a rapidly growing interest because this paradigm holds promise for improving the therapeutic efficacy of anticancer therapy. However, the current drug combination therapy refers to administering individual drugs together, which is far from a perfect regimen for cancer patients. The aim of this work was to demonstrate that synergistic delivery of two chemotherapeutic drugs in a single nanoparticle reservoir could be achieved through the rational chemical ligation of the drugs followed by supramolecular nano-assembly via blending of the drugs with a minimal amount of matrix. Choosing 7-ethyl-10-hydroxycamptothecin and taxanes, which are rich in aromatic structures, as model compounds, we show that the heterodimeric conjugates of the two agents are miscible with lipids to form systemically injectable nanomedicines. The compatibility between the prodrug conjugates and lipid carriers is substantially augmented by the intermolecular π-π stacking and alleviated polarity, thus enabling an exceptionally high drug loading (DL) capacity (~92%) and a gratifyingly long drug retention time within the micellar core. We further observed superior therapeutic outcomes in a mouse tumor model without detecting accompanying systemic toxicity. This structure-based, self-assembled cancer nanomedicine increased the potency and drug tolerability in animals and thus offers a robust strategy for simultaneously formulating two or more drugs in single nanovehicles.