3D Printed MXene-Based Wire Strain Sensors with Enhanced Sensitivity and Anisotropy.

Stretchable strain sensors play a crucial role in intelligent wearable systems, serving as the interface between humans and environment by translating mechanical strains into electrical signals. Traditional fiber strain sensors with intrinsic uniform axial strain distribution face challenges in achieving high sensitivity and anisotropy. Moreover, existing micro/nano-structure designs often compromise stretchability and durability. To address these challenges, a novel approach of using 3D printing to fabricate MXene-based flexible sensors with tunable micro and macrostructures.  Poly(tetrafluoroethylene) (PTFE) as a pore-inducing agent is added into 3D printable inks to achieve controllable microstructural modifications. In addition to microstructure tuning, 3D printing is employed for macrostructural design modifications, guided by finite element modeling (FEM) simulations. As a result, the 3D printed sensors exhibit heightened sensitivity and anisotropy, making them suitable for tracking static and dynamic displacement changes. The proposed approach presents an efficient and economically viable solution for standardized large-scale production of advanced wire strain sensors.

Ultrasound-Triggered Azo Free Radicals for Cervical Cancer Immunotherapy.

PD-1 blockade is a first-line treatment for recurrent/metastatic cervical cancer but benefits only a small number of patients due to low preexisting tumor immunogenicity. Using immunogenic cell death (ICD) inducers is a promising strategy for improving immunotherapy, but these compounds are limited by the hypoxic environment of solid tumors. To overcome this issue, the nanosensitizer AIBA@MSNs were designed based on sonodynamic therapy (SDT), which induces tumor cell death under hypoxic conditions through azo free radicals in a method of nonoxygen radicals. Mechanistically, the azo free radicals disrupt both the structure and function of tumor mitochondria by reversing the mitochondrial membrane potential and facilitating the collapse of electron transport chain complexes. More importantly, the AIBA@MSN-based SDT serves as an effective ICD inducer and improves the antitumor immune capacity. The combination of an AIBA@MSN-based SDT with a PD-1 blockade has the potential to improve response rates and provide protection against relapse. This study provides insights into the use of azo free radicals as a promising SDT strategy for cancer treatment and establishes a basic foundation for nonoxygen-dependent SDT-triggered immunotherapy in cervical cancer treatment.

Stress/cell death pathways, neuroinflammation, and neuropathic pain.

Neuropathic pain is a common and debilitating modality of chronic pain induced by a lesion or disease of the somatosensory nervous system. Albeit the elucidation of numerous pathophysiological mechanisms and the development of potential treatment compounds, safe and reliable therapies of neuropathic pain remain poor. Multiple stress/cell death pathways have been shown to be implicated in neuroinflammation during neuropathic pain. Here, we summarize the current knowledge of stress/cell death pathways and present an overview of the roles and molecular mechanisms of stress/cell death pathways in neuroinflammation during neuropathic pain, covering intrinsic and extrinsic apoptosis, autophagy, mitophagy, ferroptosis, pyroptosis, necroptosis, and phagoptosis. Small molecule compounds that modulate stress/cell death pathways in alleviating neuropathic pain are discussed mainly based on preclinical neuropathic pain models. These findings will contribute to in-depth understanding of the pathological processes during neuropathic pain as well as bridge the gap between basic and translational research to uncover new neuroprotective interventions.

Preparation of Well-Constructed and Metal-Modified Covalent Organic Framework Nanoparticles for Biosensing Design with Cascade Catalytic Capability.

Uniform covalent organic framework nanoparticles (COF NPs) with a well-defined pore structure may provide a robust platform for scaffolding enzymes. Herein, bipyridine-based spherical COF NPs have been successfully prepared in this work through the Schiff base condensation reaction. Moreover, they are functionalized by metal modification and are further used for biosensor fabrication. Experimental results reveal that the metal-modified COF NPs also display impressive peroxidase-like catalytic activities, while they can load enzymes, such as glucose oxidase (GOx) and sarcosine oxidase (SOx), to develop a cascade catalysis system for design of various kinds of biosensors with very well performance. For example, the optimized GOx@Fe-COFs can achieve a sensitive detection of glucose with a low limit of detection (LOD) of 12.8 µM. Meanwhile, the enzymes also exhibit a commendable preservation of 80% enzymatic activity over a span of 14 days under ambient conditions. This work may pave the way for advancing cascade catalysis and the analysis of different kinds of biological molecules based on COF NPs.

Interactions of Indoleamine 2,3-dioxygenase-expressing LAMP3+ dendritic cells with CD4+ regulatory T cells and CD8+ exhausted T cells: synergistically remodeling of the immunosuppressive microenvironment in cervical cancer and therapeutic implications.

BACKGROUND: Cervical cancer (CC) is the fourth most common cancer in women worldwide. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of CC immune remodeling and exploration of novel treatment targets. This study aimed to investigate the mechanism of CC immune remodeling and explore potential therapeutic targets. METHODS: We conducted single-cell RNA sequencing on a total of 17 clinical specimens, including normal cervical tissues, high-grade squamous intraepithelial lesions, and CC tissues. To validate our findings, we conducted multicolor immunohistochemical staining of CC tissues and constructed a subcutaneous tumorigenesis model in C57BL/6 mice using murine CC cell lines (TC1) to evaluate the effectiveness of combination therapy involving indoleamine 2,3-dioxygenase 1 (IDO1) inhibition and immune checkpoint blockade (ICB). We used the unpaired two-tailed Student's t-test, Mann-Whitney test, or Kruskal-Wallis test to compare continuous data between two groups and one-way ANOVA with Tukey's post hoc test to compare data between multiple groups. RESULTS: Malignant cervical epithelial cells did not manifest noticeable signs of tumor escape, whereas lysosomal-associated membrane protein 3-positive (LAMP3+ ) dendritic cells (DCs) in a mature state with immunoregulatory roles were found to express IDO1 and affect tryptophan metabolism. These cells interacted with both tumor-reactive exhausted CD8+ T cells and CD4+ regulatory T cells, synergistically forming a vicious immunosuppressive cycle and mediating CC immune escape. Further validation through multicolor immunohistochemical staining showed co-localization of neoantigen-reactive T cells (CD3+ , CD4+ /CD8+ , and PD-1+ ) and LAMP3+ DCs (CD80+ and PD-L1+ ). Additionally, a combination of the IDO1 inhibitor with an ICB agent significantly reduced tumor volume in the mouse model of CC compared with an ICB agent alone. CONCLUSIONS: Our study suggested that a combination treatment consisting of targeting IDO1 and ICB agent could improve the therapeutic efficacy of current CC immunotherapies. Additionally, our results provided crucial insights for designing drugs and conducting future clinical trials for CC.

A peptides-based biosensor with target-triggered charge-switchable property for simple and sensitive detection of Granzyme B.

Granzyme B (GrB) is a serine protease released by natural killer cells and cytotoxic T lymphocytes during immune responses, which not only plays a role in tumor diagnosis but also provides valuable guidance during tumor treatment. In this work, we have designed a charge-switching peptide to fabricate an electrochemical biosensor for quantitative analysis of GrB. Specifically, the designed zwitterionic peptide is in an electrically neutral state before activation, and a door lock structure (proline) is constructed by utilizing the selectivity of carboxypeptidase A (CPA) to the carboxy-terminus of the peptide chain. The door lock is opened when the target is present, allowing CPA to hydrolyze the peptide. At this time, the peptide will convert from neutral to positive, triggering the assembly of a positively charged peptide layer on the electrode surface, resulting in a signal change. Studies have shown that the biosensor has good analytical performance, with a detection range of 0.01 pM-8 pM and a detection limit as low as 3.5 fM. Moreover, the developed biosensor has been effectively applied to the analysis of clinical samples, demonstrating its ability to monitor tumor progression and treatment with clinical applications.

Ferroptosis: a new regulatory mechanism in neuropathic pain.

Neuropathic pain (NP) is pain caused by damage to the somatosensory system. It is a common progressive neurodegenerative disease that usually presents with clinical features such as spontaneous pain, touch-evoked pain, nociceptive hyperalgesia, and sensory abnormalities. Due to the complexity of the mechanism, NP often persists. In addition to the traditionally recognized mechanisms of peripheral nerve damage and central sensitization, excessive iron accumulation, oxidative stress, neuronal inflammation, and lipid peroxidation damage are distinctive features of NP in pathophysiology. However, the mechanisms linking these pathological features to NP are not fully understood. The complexity of the pathogenesis of NP greatly limits the development of therapeutic approaches for NP. Ferroptosis is a novel form of cell death discovered in recent years, in which cell death is usually accompanied by massive iron accumulation and lipid peroxidation. Ferroptosis-inducing factors can affect glutathione peroxidase directly or indirectly through different pathways, leading to decreased antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in cells, ultimately leading to oxidative cell death. It has been shown that ferroptosis is closely related to the pathophysiological process of many neurological disorders such as NP. Possible mechanisms involved are changes in intracellular iron ion levels, alteration of glutamate excitability, and the onset of oxidative stress. However, the functional changes and specific molecular mechanisms of ferroptosis during this process still need to be further explored. How to intervene in the development of NP by regulating cellular ferroptosis has become a hot issue in etiological research and treatment. In this review, we systematically summarize the recent progress of ferroptosis research in NP, to provide a reference for further understanding of its pathogenesis and propose new targets for treatment.

Revisiting molecularly conformation-planarized organic dyes for NIR-II fluorescence imaging.

Fluorescence imaging in the second window (NIR-II, 1000-1700 nm) provides deeper penetration depth and higher resolution, but there is still a dilemma for designing NIR-II dyes for simultaneously enhancing fluorescence efficiency and prolonging excitation wavelength. Herein, a molecular conformation planarization strategy has been revisited to guide the synthesis of two donor-acceptor-donor dyes (named T-BBT and BT-BBT). On the one hand, conformational planarization can extend the absorption peaks of T-BBT and BT-BBT to the NIR region with high molar extinction coefficients of 30.5 × 103 and 16.4 × 103 L (mol-1 cm-1) at 1064 nm, respectively. On the other hand, structural rigidity can weaken electronic vibration coupling-related non-radiative decay pathways, whereby both T-BBT and BT-BBT display rather high fluorescence efficiencies of 3.6% and 13.5% in solution. Furthermore, a molecular doping strategy is adopted to alleviate fluorescence quenching in the aggregated state by suppressing long-distance energy migration, and 2.5 wt% doped BT-BBT nanoparticles show a high fluorescence efficiency of 2.0%, which enables the application of in vivo deep NIR-II fluorescence imaging for vessels and tumors with high resolution under 980 nm excitation. This work demonstrates that organic dyes with structural planarization can bridge the gap between NIR-II absorption and fluorescence efficiency.

PtMo-Au Metalloenzymes Regulated Tumor Microenvironment for Enhanced Sonodynamic/Chemodynamic/Starvation Synergistic Therapy.

The clinical application of sonodynamic therapy (SDT) is greatly limited by the low quantum yield of sonosensitizers and tumor microenvironment (TME). Herein, PtMo-Au metalloenzyme sonosensitizer is synthesized by modulating energy band structure of PtMo with Au nanoparticles. The surface deposition of Au simultaneously solves the carrier recombination and facilitates the separation of electrons (e- ) and holes (h+ ), effectively improving the reactive oxygen species (ROS) quantum yield under ultrasound (US). The catalase-like activity of PtMo-Au metalloenzymes alleviates hypoxia TME, thus enhancing the SDT-induced ROS generation. More importantly, tumor overexpressed glutathione (GSH) can serve as the hole scavenger, which is accompanied by a persistent depletion of the GSH, thus inactivating GPX4 for the accumulation of lipid peroxides. The distinctly facilitated SDT-induced ROS production is coupled with chemodynamic therapy (CDT)-induced hydroxyl radicals (•OH) to exacerbate ferroptosis. Furthermore, Au with glucose oxidase mimic activity can not only inhibit intracellular adenosine triphosphate (ATP) production and induce tumor cell starvation but also generate H2 O2 to facilitate CDT. In general, this PtMo-Au metalloenzyme sonosensitizer optimizes the defects of conventional sonosensitizers through surface deposition of Au to regulate TME, providing a novel perspective for US-based tumor multimodal therapy.

Iodide-Enhanced Perovskite Nanozyme-Based Colorimetric Platform for Detection of Urinary Nuclear Matrix Protein 22.

In the last decade, perovskite nanocrystals (PNCs) have brought extensive thinking owing to their excellent optical properties. Recently, we have uncovered the peroxidase-like activity of PNCs and used this for detecting many small molecules; however, the low enzymatic activity makes them unsuitable for fluorescence analysis, which is easily disturbed by the autofluorescence of biological media. This greatly limits their application in bioanalysis. Thus, the development of a method to facilely modulate the activity of PNCs for the instrument-free colorimetric detection is highly desirable. Herein, we demonstrated an iodide-enhanced perovskite nanozyme-based colorimetric platform for the visual assay of urinary nuclear matrix protein 22 (NMP22), a typical biomarker for the diagnosis of bladder cancer. We discovered that halogen could regulate the activity of perovskite nanozymes through a simple anion replacement reaction. Experimental analysis suggested that CsPbI3 nanocrystals (NCs) displayed 24-fold higher catalytic efficiency than classical CsPbBr3 NCs. As a proof-of-concept assay, the CsPbI3 NCs could be explored into an immunoassay for the detection of NMP22 in clinical urine specimens, resulting in a low detection limit of 0.03 U/mL. This iodide-enhanced immunoassay deepens our understanding of perovskite nanozymes and also provides great potential for bioanalysis.

Engineered Escherichia coli as a Controlled-Release Biocarrier for Electrochemical Immunoassay.

Micro/nanocarriers hold great potential in bioanalysis for molecular recognition and signal amplification but are frequently hampered by harsh synthesis conditions and time-consuming labeling processes. Herein, we demonstrate that Escherichia coli (Ec) can be engineered as an efficient biocarrier for electrochemical immunoassay, which can load ultrahigh amounts of redox indicators and simultaneously be decorated with detection antibodies via a facile polydopamine (PDA)-mediated coating approach. Compared with conventional carrier materials, the entire preparation of the Ec biocarrier is simple, highly sustainable, and reproducible. Moreover, immune recognition and electrochemical transduction are performed independently, which eliminates the accumulation of biological interference on the electrode and simplifies electrode fabrication. Using human epidermal growth factor receptor 2 (HER2) as the model target, the proposed immunosensor exhibits excellent analytical performance with a low detection limit of 35 pg/mL. The successful design and deployment of Ec biocarrier may provide new guidance for developing biohybrids in biosensing applications.

In situ rapid synthesis of hydrogels based on a redox initiator and persistent free radicals.

The development of fast and economical hydrogel manufacturing methods is crucial for expanding the application of hydrogels. However, the commonly used rapid initiation system is not conducive to the performance of hydrogels. Therefore, the research focuses on how to improve the preparation speed of hydrogels and avoid affecting the properties of hydrogels. Herein, a redox initiation system with nanoparticle-stabilized persistent free radicals was introduced to rapidly synthesize high-performance hydrogels at room temperature. A redox initiator composed of vitamin C and ammonium persulfate rapidly provides hydroxyl radicals at room temperature. Simultaneously, three-dimensional nanoparticles can stabilize free radicals and prolong their lifetime, thereby increasing the free radical concentration and accelerating the polymerization rate. And casein enabled the hydrogel to achieve impressive mechanical properties, adhesion, and electrical conductivity. This method greatly facilitates the rapid and economical synthesis of high-performance hydrogels and presents broad application prospects in the field of flexible electronics.

Extracellular Vesicles as Biomarkers in Head and Neck Squamous Cell Carcinoma: From Diagnosis to Disease-Free Survival.

Head and neck squamous cell carcinomas (HNSCCs) arising from different anatomical sites present with different incidences and characteristics, which requires a personalized treatment strategy. Despite the extensive research that has conducted on this malignancy, HNSCC still has a poor overall survival rate. Many attempts have been made to improve the outcomes, but one of the bottlenecks is thought to be the lack of an effective biomarker with high sensitivity and specificity. Extracellular vesicles (EVs) are secreted by various cells and participate in a great number of intercellular communications. Based on liquid biopsy, EV detection in several biofluids, such as blood, saliva, and urine, has been applied to identify the existence and progression of a variety of cancers. In HNSCC, tumor-derived EVs exhibit many functionalities by transporting diverse cargoes, which highlights their importance in tumor screening, the determination of multidisciplinary therapy, prediction of prognosis, and evaluation of therapeutic effects. This review illustrates the classification and formation of EV subtypes, the cargoes conveyed by these vesicles, and their respective functions in HNSCC cancer biology, and discloses their potential as biomarkers during the whole process of tumor diagnosis, treatment, and follow-up.

Influence of human activities and climate change on wetland landscape pattern-A review.

Wetlands (rivers, lakes, swamps, etc.) are biodiversity hotspots, providing habitats for biota on the earth. In recent years, wetlands have been significantly affected by human activities and climate change, and wetland ecosystems have become one of the most threatened ecosystems in the world. There have been many studies on the impact of human activities and climate change on wetland landscapes, but there is still a lack of relevant reviews. This article summarizes the research on the impact of global human activities and climate change on wetland landscape patterns (vegetation distribution, etc.) from 1996 to 2021. Human activities such as dam construction, urbanization, and grazing will significantly affect the wetland landscape. Generally, dam construction and urbanization are generally believed to harm wetland vegetation, but appropriate human behaviors such as tillage benefit wetland plants' growth on reclaimed land. Prescribed fires in non-inundation periods are one of the ways to increase the vegetation coverage and diversity of wetlands. In addition, some ecological restoration projects have a positive impact on wetland vegetation (quantity, richness, etc.). Under climatic conditions, extreme floods and droughts are likely to change the wetland landscape pattern, and excessively high and low water levels will restrict plants. At the same time, the invasion of alien vegetation will inhibit the growth of native vegetation in the wetland. In an environment of global warming, rising temperatures may be a "double-edged sword" for alpine and higher latitude wetland plants. This review will help researchers better understand the impact of human activities and climate change on wetland landscape patterns and suggests avenues for future studies.

Spatiotemporally deciphering the mysterious mechanism of persistent HPV-induced malignant transition and immune remodelling from HPV-infected normal cervix, precancer to cervical cancer: Integrating single-cell RNA-sequencing and spatial transcriptome.

BACKGROUND: The mechanism underlying cervical carcinogenesis that is mediated by persistent human papillomavirus (HPV) infection remains elusive. AIMS: Here, for the first time, we deciphered both the temporal transition and spatial distribution of cellular subsets during disease progression from normal cervix tissues to precursor lesions to cervical cancer. MATERIALS & METHODS: We generated scRNA-seq profiles and spatial transcriptomics data from nine patient samples, including two HPV-negative normal, two HPV-positive normal, two HPV-positive HSIL and three HPV-positive cancer samples. RESULTS: We not only identified three 'HPV-related epithelial clusters' that are unique to normal, high-grade squamous intraepithelial lesions (HSIL) and cervical cancer tissues but also discovered node genes that potentially regulate disease progression. Moreover, we observed the gradual transition of multiple immune cells that exhibited positive immune responses, followed by dysregulation and exhaustion, and ultimately established an immune-suppressive microenvironment during the malignant program. In addition, analysis of cellular interactions further verified that a 'homeostasis-balance-malignancy' change occurred within the cervical microenvironment during disease progression. DISCUSSION: We for the first time presented a spatiotemporal atlas that systematically described the cellular heterogeneity and spatial map along the four developmental steps of HPV-related cervical oncogenesis, including normal, HPV-positive normal, HSIL and cancer. We identified three unique HPV-related clusters, discovered critical node genes that determined the cell fate and uncovered the immune remodeling during disease escalation. CONCLUSION: Together, these findings provided novel possibilities for accurate diagnosis, precise treatment and prognosis evaluation of patients with precancer and cervical cancer.

Single-Cell Landscape Highlights Heterogenous Microenvironment, Novel Immune Reaction Patterns, Potential Biomarkers and Unique Therapeutic Strategies of Cervical Squamous Carcinoma, Human Papillomavirus-Associated (HPVA) and Non-HPVA Adenocarcinoma.

Cervical adenocarcinomas (ADCs), including human papillomavirus (HPV)-associated (HPVA) and non-HPVA (NHPVA), though exhibiting a more malignant phenotype and poorer prognosis, are treated identically to squamous cell carcinoma (SCC). This clinical dilemma requires a deeper investigation into their differences. Herein a transcriptomic atlas of SCC, HPVA, and NHPVA-ADC using single-cell RNA (scRNA) and T-cell receptor sequencing (TCR-seq) is presented. Regarding structural cells, the malignancy origin of epithelial cells, angiogenic tip cells and two subtypes of fibroblasts is revealed. The promalignant properties of the structural cells using organoids are further confirmed. Regarding immune cells, myeloid cells with multiple functions other than antigen presentation and exhausted T lymphocytes contribute to immunosuppression. From the perspective of HPV infection, not only is HPV-dependent and independent cervical cancer oncogenesis proposed but also three immune reaction patterns mediated by T cells (coordinated/inactive/imbalanced) are identified. Strikingly, diagnostic biomarkers to distinguish ADC from SCC are discovered and prognostic biomarkers with marker genes for malignant epithelial cells, tip cells, and SPP1/C1QC macrophages are generated. Importantly, the efficacy of anti-CD96 and anti-TIGIT, not inferior to anti-PD1, in animal experiments is confirmed and targeted therapies specifically for HPV-positive SCC, HPVA and NHPVA-ADC, providing essential clues for further clinical trials, are proposed.

Convergent dysbiosis of upper aerodigestive microbiota between patients with esophageal and oral cavity squamous cell carcinoma.

The bidirectional association between primary esophageal squamous cell carcinoma (ESCC) and oral cavity squamous cell carcinoma (OSCC) suggests common risk factors and oncogenic molecular processes but it is unclear whether these two cancers display similar patterns of dysbiosis in their upper aerodigestive microbiota (UADM). We conducted a case-control study to characterize the microbial communities in esophageal lavage samples from 49 ESCC patients and oral rinse samples from 91 OSCC patients using 16S rRNA V3-V4 amplicon sequencing. Compared with their respective non-SCC controls from the same anatomical sites, 32 and 45 discriminative bacterial genera were detected in ESCC and OSCC patients, respectively. Interestingly, 20 of them were commonly enriched or depleted in both types of cancer, suggesting a convergent niche adaptation of upper aerodigestive SCC-associated bacteria that may play important roles in the pathogenesis of malignancies. Notably, Fusobacterium, Selenomonas, Peptoanaerobacter and Peptostreptococcus were enriched in both ESCC and OSCC, whereas Streptococcus and Granulicatelia were commonly depleted. We further identified Fusobacterium nucleatum as the most abundant species enriched in the upper aerodigestive SCC microenvironment, and the higher relative abundances of Selenomonas danae and Treponema maroon were positively correlated with smoking. In addition, predicted functional analysis revealed several depleted (eg, lipoic acid and pyruvate metabolism) and enriched (eg, RNA polymerase and nucleotide excision repair) pathways common to both cancers. Our findings reveal a convergent dysbiosis in the UADM between patients with ESCC and OSCC, suggesting a shared niche adaptation of host-microbiota interactions in the pathogenesis of upper aerodigestive tract malignancies.

Robust Neural Interfaces with Photopatternable, Bioadhesive, and Highly Conductive Hydrogels for Stable Chronic Neuromodulation.

A robust neural interface with intimate electrical coupling between neural electrodes and neural tissues is critical for stable chronic neuromodulation. The development of bioadhesive hydrogel neural electrodes is a potential approach for tightly fixing the neural electrodes on the epineurium surface to construct a robust neural interface. Herein, we construct a photopatternable, antifouling, conductive (∼6 S cm-1), bioadhesive (interfacial toughness ∼100 J m-2), soft, and elastic (∼290% strain, Young's modulus of 7.25 kPa) hydrogel to establish a robust neural interface for bioelectronics. The UV-sensitive zwitterionic monomer can facilitate the formation of an electrostatic-assembled conductive polymer PEDOT:PSS network, and it can be further photo-cross-linked into elastic polymer network. Such a semi-interpenetrating network endows the hydrogel electrodes with good conductivity. Especially, the photopatternable feature enables the facile microfabrication processes of multifunctional hydrogel (MH) interface with a characteristic size of 50 µm. The MH neural electrodes, which show improved performance of impedance, charge storage capacity, and charge injection capability, can produce effective electrical stimulation with high current density (1 mA cm-2) at ultralow voltages (±25 mV). The MH interface could realize high-efficient electrical communication at the chronic neural interface for stable recording and stimulation of a sciatic nerve in the rat model.

Intraoperative frozen pathology exam of Common iliac lymph nodes and Para-Aortic lymphadenectomy on the prognosis and quality of life for patients with IB2-IIA2 Cervical Cancer: trial protocol for a randomized controlled trial (C-PACC trial).

BACKGROUND: The impact of para-aortic lymphadenectomy (PALD) on prognosis and quality of life (QoL) for IB2-IIA2 cervical cancer patients remain controversial. And whether intraoperative frozen pathology exam on common iliac lymph nodes could help predict para-aortic lymph node (PALN) metastasis was unanswered with high-level evidence. METHODS: A multi-center, randomized controlled study is intended to investigate the effect of PALD on the prognosis and QoL in cervical cancer patients and to assess the value of intraoperative frozen pathological evaluation of common iliac nodes metastasis for the prediction of PALN metastasis. After choosing whether to receive intraoperative frozen pathological examination of bilateral common iliac lymph nodes, eligible patients will be randomly assigned (1:1) to receive PALD or not. The primary end point is 2-year progression-free survival (PFS). The secondary end points include 5-year PFS, 2-year overall survival (OS), 5-year OS, adverse events (AEs) caused by PALD, AEs caused by radiotherapy and QoL. A total of 728 patients will be enrolled from 8 hospitals in China within 3-year period and followed up for 5 years. TRIAL REGISTRATION: Chinese Clinical Trial Register Identifier: ChiCTR2000035668.

Metal-free polymer nano-photosensitizer actuates ferroptosis in starved cancer.

The microenvironment in solid tumors drives the fate of cancer cells to ferroptosis, yet the underlying mechanism remains incompletely understood. Herein, we report a metal-free polymer photosensitizer (BDPB) as a new type ferroptosis inducer of starved cancer cells. The polymer consists of boron difluoride dipyrromethene dye as the photosensitizing unit and diisopropyl-ethyl amine as the electron-donating unit. Ultrafast spectroscopy and electron spin resonance mechanistically revealed the prolonged charge-separation process in BDPB, enabling complex-I like one-electron transfer effect to produce O2●-. Unexpectedly, the O2●--generating BDPB nanoparticles (NPs) served to deactivate the AMPK-mTOR signaling pathway in normal-state cancer cells to initiate cell repair activity and survive low-dose phototherapy. However, for cancer cells in a starved state, BDPB NPs triggered glutathione peroxidase 4 downregulation, lipid peroxides accumulation, and death to cancer cells, which was identified as ferroptosis but not apoptosis, necroptosis, or autosis. The application of BDPB NPs sheds new light on the design of individualized ferroptosis inducers for combating cancer progression.