Zhonghua Liu

Cholangiocarcinoma (CCA) is a malignant tumor arising from the epithelial cells of the biliary tract. It is characterized by high heterogeneity, frequent late diagnosis, high rates of metastasis, and overall poor prognosis. Unfortunately, the development of sensitive biomarkers and effective therapeutic approaches remains challenging and an unmet need. In recent years, advances in molecular biological techniques have significantly enhanced our understanding of the molecular mechanisms underlying CCA pathogenesis. This review summarized the biomarkers identified in CCA, highlighted the critical genes and signal transduction pathways closely associated with tumor cell proliferation and migration, inflammation regulation, angiogenesis, and tumor microenvironment, and discussed the complex regulatory roles of epigenetic alterations in CCA initiation and progression. These recent insights not only deepen our understanding of the molecular complexity of CCA but also lay a solid foundation for the development of precision medicine and individualized therapeutic strategies for patients with this aggressive malignancy.

Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases and is one of the leading causes of cancer-related death worldwide. Although traditional therapies such as chemotherapy, radiotherapy and molecular targeted therapy, as well as immunotherapy, have made substantial progress, drug resistance and tumour recurrence remain significant challenges. Immunogenic cell death (ICD), a special type of cell death, has emerged as a cutting-edge strategy for NSCLC treatment due to its unique immune activation mechanism. ICD orchestrates immunogenic tumour cell death via coordinated endoplasmic reticulum stress and reactive oxygen species generation, resulting in the release of damage-associated molecular patterns (DAMPs). Through a synergistic mechanism, tumour-associated antigens are unveiled, antigen-presenting cells such as dendritic cells are activated, and T cell responses targeting tumour-specific antigens are triggered. These factors collectively act to reprogramme the immunosuppressive tumour microenvironment (TME). Preclinical trials have demonstrated that chemotherapy, radiotherapy and molecular targeted therapy enhance the antitumour effect by inducing ICD, providing new strategies for treating NSCLC. This review systematically summarises the induction strategies of ICD in the treatment of NSCLC and focuses on the progress in preclinical experiments and clinical trials. Additionally, the current paper discusses the core challenges and future development directions of ICD in NSCLC therapy, to provide novel insights into the optimised utilisation and clinical implementation of ICD induction strategies.

Idiopathic pulmonary fibrosis, an idiopathic interstitial lung disease with high mortality, remains challenging to treat due to the lack of clinically approved lung-targeting drugs. Herein, we present PDIC-DPC, a perylenediimide derivative that exhibits superior lung-selective enrichment. PDIC-DPC forms nanocomposites with plasma proteins, including fibrinogen beta chain and vitronectin, which bind to pulmonary endothelial receptors for lung-specific accumulation. Moreover, PDIC-DPC significantly suppresses transforming growth factor beta1 and activates adenosine monophosphate-activated protein kinase. As a result, compared to existing therapeutic drugs, PDIC-DPC achieves superior therapeutic outcomes, evidenced by the lowest Ashcroft score, significantly improved pulmonary function, and an extended survival rate in a bleomycin-induced pulmonary fibrosis model. This study elucidates the lung-selective enrichment of assembled prodrug from biological perspectives and affords a platform enabling therapeutic efficiency on idiopathic pulmonary fibrosis.

Broaching is the most important processing technology of mortise and tenon of aviation turbine disk. The precision of broaching equipment determines the processing quality of mortise and tenon. According to the principle of multi-body kinematics and the homogeneous coordinate transformation, the mathematical model of static accuracy analysis of the five-axis aircraft turbine disk tenon broaching machine is established, and the tool setting error matrix is derived. Monte Carlo method was used to obtain the statistical distribution of errors in line with the assembly requirements and motion accuracy, and the simulation model of the tool process was built to complete the prediction of the static accuracy of the broaching machine. The influence of various errors in motion on the sensitivity of the tool accuracy was analyzed systematically.

High‐performance photothermal theranostics is urgently desired for cancer therapy because of their good controllability and noninvasive features. The relatively low photothermal conversion efficiency is still at the drawbacks because of the absence of efficient extraneous carriers. Herein, a carrier‐free nanomedicine is developed to in vivo self‐deliver organic photothermal agents for efficient cancer phototheranostics. By a facile self‐assembly strategy, the near‐infrared (NIR)‐absorbing conjugated oligomer IDIC‐4F is fabricated into a carrier‐free nanoparticle (DCF‐P), showing ultrasmall size of nearly 4.0 nm with a nearly 100% of drug loading capacity. Notably, DCF‐P achieves a superhigh photothermal conversion efficiency of 80.5% that is far greater than that of IDIC‐4F‐loaded nanomicelle DCF‐M (57.3%). With the guidance of NIR fluorescence and photoacoustic dual‐imaging, it is verified that DCF‐P could well achieve tumor‐preferential accumulation and retention at 4 h postinjection, and meanwhile shows highly efficient in vivo tumor elimination with good biosafety. This study thus contributes a novel concept for designing ultrasmall nanoparticle characteristics of preferential accumulation in tumors, and also provides a strategy for creating high‐performance carrier‐free nanomedicine via highly ordered molecular stacking.

Photothermal therapy is promising for augmenting cancer therapeutic outcomes in cancer treatment. Diketopyrrolopyrrole (DPP)-conjugated polymer nanoparticles are in focus due to their dual photoacoustic imaging and photothermal therapy functions. Herein, the design and synthesis of three near-infrared absorbing conjugated polymers, named DPP-SO, DPP-SS and DPP-SSe, with heteroatom substitution of the thiophene moiety were developed for a photoacoustic imaging guided photothermal therapy. It was demonstrated that systematically changing only the heteroatom from O to S or Se could apparently adjust the absorption spectrum and energy gap of DPP-conjugated polymers to obtain the most suitable photothermal transduction agents (PTAs) for use in biomedicine. The characterization of photophysical properties proved that the photothermal conversion efficiency and absorption coefficient of DPP-SO nanoparticles under 808 nm irradiation was up to 79.3% and 66.51 L g⁻¹ cm⁻¹, respectively, which were much higher than those of DPP-SS and DPP-SSe nanoparticles. Remarkably, the IC₅₀ value of DPP-SO for killing A549 cells was half that of DPP-SS and DPP-SSe nanoparticles. Further in vivo works demonstrated efficient photothermal therapeutic effects of DPP-SO nanoparticles with the guidance of photoacoustic imaging. Thus, this is an efficient method to regulate the photothermal performance of DPP-conjugated polymers by changing the heteroatom in the molecular skeleton.

Extensive recent progress has been made on the design and applications of organic photothermal agents for biomedical applications because of their excellent biocompatibility comparing with inorganic materials. One major hurdle for the further development and applications of organic photothermal agents is the rarity of high‐performance materials in the second near‐infrared (NIR‐II) window, which allows deep tissue penetration and causes minimized side effects. Up till now, there have been few reported NIR‐II‐active photothermal agents and their photothermal conversion efficiencies are relatively low. Herein, optical absorption of π‐conjugated small molecules from the first NIR window to the NIR‐II window is precisely regulated by molecular surgery of substituting an individual atom. With this technique, the first demonstration of a conjugated oligomer (IR‐SS) with an absorption peak beyond 1000 nm is presented, and its nanoparticle achieves a record‐high photothermal conversion efficiency of 77% under 1064 nm excitation. The nanoparticles show a good photoacoustic response, photothermal therapeutic efficacy, and biocompatibility in vitro and in vivo. This work develops a strategy to boost the light‐harvesting efficiency in the NIR‐II window for cancer theranostics, offering an important step forward in advancing the design and application of NIR‐II photothermal agents.

Thionated perylenediimides (PDIs) can potentially generate thermal and reactive oxygen species and thus can be used as theranostic agents for photothermal/photodynamic therapy. Herein, thionated cis-/trans-isomer PDI-CS and PDI-TS were designed and prepared to investigate thionation engineering on therapeutic performance. The results revealed that the photodynamic performance is less associated with the positon of sulfur atoms. By contrast, trans-isomer PDI-TS showed a photothermal conversion efficiency of up to 58.4%, which was 40% higher than that of PDI-CS (∼41.6%). An in vitro half-maximal inhibitory concentration of ∼7.78 μg mL⁻¹ was achieved for PDI-TS, which was 1.7-fold smaller than that of PDI-CS, strongly reasserting the regioisomer-modulated phototheranostic performance. Notably, the strong π–π and C⋯S interactions in PDI-TS nanoagents are essential factors attributed to their excellent photothermal performance, indicating that the optimization of non-bonding interactions is an ingenious way to improve phototheranostic performance. This work provides a facile means of creating thio-perylenediimides that possess excellent antitumor properties and a novel proof of concept to improve therapeutic performance through the optimization of non-bonding interactions.