Reactive Oxygen Species Amplifier for Apoptosis-Ferroptosis Mediated High-Efficiency Radiosensitization of Tumors.

Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development of a biomaterial capable of activating ROS-induced apoptosis and ferroptosis is a potential strategy to enhance RT sensitivity. To achieve precision and high-efficiency RT, the theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, and inducing apoptosis-ferroptosis to sensitize RT. A large amount of ROS is derived from three aspects: (1) When exposed to ionizing radiation, Au/CuNDs effectively absorb photons and emit various electrons, which can interact with water to produce ROS. (2) Au/CuNDs act as a catalase-like to produce abundant ROS through Fenton reaction with hydrogen peroxide overexpressed of tumor cells. (3) Au/CuNDs deplete overexpressed glutathione, which causes the accumulation of ROS. Large amounts of ROS and ionizing radiation further lead to apoptosis by increasing DNA damage, and ferroptosis by enhancing lipid peroxidation, significantly improving the therapeutic efficiency of RT. Furthermore, Au/CuNDs serve as an excellent nanoprobe for high-resolution near-infrared fluorescence imaging and computed tomography of tumors. The promising dual-mode imaging performance shows their potential application in clinical cancer detection and imaging-guided precision RT, minimizing damage to adjacent normal tissues during RT. In summary, our developed theranostic nanoplatform integrates dual-mode imaging and sensitizes RT via ROS-activated apoptosis-ferroptosis, offering a promising prospect for clinical cancer diagnosis and treatment.

Efficient Removal of Iodine from Water by a Calix[4]pyrrole-Based Nanofilm.

The efficient removal of radioactive iodine from an aqueous solution is largely dependent on the adsorbent materials employed. In this work, we report a calix[4]pyrrole-based nanofilm and its application for the rapid removal of iodine from water. The nanofilm was synthesized through a confined dynamic condensation of tetra hydrazide calix[4]pyrrole with 1,3,5-tri-(4-formylphenyl) aldehyde at the air/dimethyl sulfoxide (DMSO) interface. The thickness of the obtained nanofilm is ∼35 nm, enabling fast mass transfer and a high ratio of accessible binding sites for iodine. The pseudo-second-order rate constant of the nanofilm for iodine is ∼0.061 g g-1 min-1, 3 orders of magnitude higher than most reported adsorbent materials. Flow-through nanofiltration tests demonstrated that the nanofilm has an adsorption capacity of 1.48 g g-1, a high removal efficiency, and good reusability. The mechanism study revealed that the moieties of Schiff base, pyrrole, and aromatic rings play a key role for binding iodine. We believe this work provides not only a new strategy for the efficient removal of radioactive iodine from water but also new ideas for designing efficient iodine adsorbents.

Preventive effect of human umbilical cord mesenchymal stem cells on skin aging in rats.

The irreversibility of aging makes anti-aging become an important research direction in the field of medical research. As the most direct manifestation of human aging, skin aging has been paid more and more attention. Stem cells have been used as a basis for anti-aging studies in skin, of which adipose-derived mesenchymal stem cells are more commonly used. In this study, human umbilical cord mesenchymal stem cells were used, and human umbilical cord mesenchymal stem cells were intervened while making a skin aging model, which was planned to reduce the process of preventing skin aging in the study method. At the end of the experiment, rat skin and serum were taken for relevant data detection. The results showed that the contents of EGF and VEGF in serum and skin tissue of rats increased and the content of MDA decreased after the application of human umbilical cord mesenchymal stem cells. At the same time, hUCMSC intervention increased skin thickness, increased dermal vessels, increased type I collagen type III collagen mRNA expression, and decreased MMP-1 content in rats. The results showed that hUCMSC could prevent skin aging in rats.

One Stone, Three Birds: Multifunctional Nanodots as "Pilot Light" for Guiding Surgery, Enhanced Radiotherapy, and Brachytherapy of Tumors.

Surgery, radiotherapy (RT), and brachytherapy are crucial treatments for localized deep tumors. However, imprecise tumor location often leads to issues such as positive surgical margins, extended radiotherapy target volumes, and radiation damage to healthy tissues. Reducing side effects in healthy tissue and enhancing RT efficacy are critical challenges. To address these issues, we developed a multifunctional theranostic platform using Au/Ag nanodots (Au/AgNDs) that act as a "pilot light" for real-time guided surgery, high-efficiency RT, and brachytherapy, achieving a strategy of killing three birds with one stone. First, dual-mode imaging of Au/AgNDs enabled precision RT, minimizing damage to adjacent normal tissue during X-ray irradiation. Au/AgNDs enhanced ionizing radiation energy deposition, increased intracellular reactive oxygen species (ROS) generation, regulated the cell cycle, promoted DNA damage formation, and inhibited DNA repair in tumor cells, significantly improving RT efficacy. Second, in brachytherapy, precise guidance provided by dual-mode imaging addressed challenges related to non-visualization of existing interstitial brachytherapy and multiple adjustments of insertion needle positions. Meanwhile, the effect of brachytherapy was improved. Third, the excellent fluorescence imaging of Au/AgNDs accurately distinguished tumors from normal tissue, facilitating their use as a powerful tool for assisting surgeons during tumor resection. Taken together, our multifunctional theranostic platform offers real-time guidance for surgery and high-efficiency RT, and improves brachytherapy precision, providing a novel strategy and vision for the clinical diagnosis and treatment of cancer.

Radiotherapy for extensive-stage small-cell lung cancer in the immunotherapy era.

Currently, chemoimmunotherapy is the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, only 0.8%-2.5% of the patients presented complete response after chemoimmunotherapy. Considering that ES-SCLC is highly sensitive to radiotherapy, the addition of radiotherapy after first-line treatment for ES-SCLC could further improve local control, which may be beneficial for patients' survival. Prior studies have shown that consolidative thoracic radiotherapy (cTRT) can decrease disease progression and improve overall survival in patients with ES-SCLC who respond well to chemotherapy. However, the efficacy and safety of cTRT in the immunotherapy era remain unclear owing to a lack of prospective studies. Prophylactic cranial irradiation (PCI) has been shown to decrease brain metastasis (BM) and prolong survival in patients with limited-stage SCLC in previous reports. However, according to current guidelines, PCI is not commonly recommended for ES-SCLC. Immunotherapy has the potential to reduce the incidence of BM. Whether PCI can be replaced with regular magnetic resonance imaging surveillance for ES-SCLC in the era of immunotherapy remains controversial. Whole brain radiation therapy (WBRT) is the standard treatment for BM in SCLC patients. Stereotactic radiosurgery (SRS) has shown promise in the treatment of limited BM. Considering the potential of immunotherapy to decrease BM, it is controversial whether SRS can replace WBRT for limited BM in the immunotherapy era. Additionally, with the addition of immunotherapy, the role of palliative radiotherapy may be weakened in patients with asymptomatic metastatic lesions. However, it is still indispensable and urgent for patients with obvious symptoms of metastatic disease, such as spinal cord compression, superior vena cava syndrome, lobar obstruction, and weight-bearing metastases, which may critically damage the quality of life and prognosis. To improve the outcome of ES-SCLC, we discuss the feasibility of radiotherapy, including cTRT, PCI, WBRT/SRS, and palliative radiotherapy with immunotherapy based on existing evidence, which may offer specific prospects for further randomized trials and clinical applications.

Role of the RNA-binding protein family in gynecologic cancers.

Gynecological cancers pose a threat to women's health. Although early-stage gynecological cancers show good outcomes after standardized treatment, the prognosis of patients with advanced, met-astatic, and recurrent cancers is poor. RNA-binding proteins (RBPs) are important cellular proteins that interact with RNA through RNA-binding domains and participate extensively in post-transcriptional regulatory processes, such as mRNA alternative splicing, polyadenylation, intracellular localization and stability, and translation. Abnormal RBP expression affects the normal function of oncogenes and tumor suppressor genes in many malignancies, thus leading to the occurrence or progression of cancers. Similarly, RBPs play crucial roles in gynecological carcinogenesis. We summarize the role of RBPs in gynecological malignancies and explore their potential in the diagnosis and treatment of cancers. The findings summarized in this review may provide a guide for future research on the functions of RBPs.

Recent Progress of Copper-Based Nanomaterials in Tumor-Targeted Photothermal Therapy/Photodynamic Therapy.

Nanotechnology, an emerging and promising therapeutic tool, may improve the effectiveness of phototherapy (PT) in antitumor therapy because of the development of nanomaterials (NMs) with light-absorbing properties. The tumor-targeted PTs, such as photothermal therapy (PTT) and photodynamic therapy (PDT), transform light energy into heat and produce reactive oxygen species (ROS) that accumulate at the tumor site. The increase in ROS levels induces oxidative stress (OS) during carcinogenesis and disease development. Because of the localized surface plasmon resonance (LSPR) feature of copper (Cu), a vital trace element in the human body, Cu-based NMs can exhibit good near-infrared (NIR) absorption and excellent photothermal properties. In the tumor microenvironment (TME), Cu2+ combines with H2O2 to produce O2 that is reduced to Cu1+ by glutathione (GSH), causing a Fenton-like reaction that reduces tumor hypoxia and simultaneously generates ROS to eliminate tumor cells in conjunction with PTT/PDT. Compared with other therapeutic modalities, PTT/PDT can precisely target tumor location to kill tumor cells. Moreover, multiple treatment modalities can be combined with PTT/PDT to treat a tumor using Cu-based NMs. Herein, we reviewed and briefly summarized the mechanisms of actions of tumor-targeted PTT/PDT and the role of Cu, generated from Cu-based NMs, in PTs. Furthermore, we described the Cu-based NMs used in PTT/PDT applications.

Epitranscriptomics in the development, functions, and disorders of cancer stem cells.

Biomolecular modifications play an important role in the development of life, and previous studies have investigated the role of DNA and proteins. In the last decade, with the development of sequencing technology, the veil of epitranscriptomics has been gradually lifted. Transcriptomics focuses on RNA modifications that affect gene expression at the transcriptional level. With further research, scientists have found that changes in RNA modification proteins are closely linked to cancer tumorigenesis, progression, metastasis, and drug resistance. Cancer stem cells (CSCs) are considered powerful drivers of tumorigenesis and key factors for therapeutic resistance. In this article, we focus on describing RNA modifications associated with CSCs and summarize the associated research progress. The aim of this review is to identify new directions for cancer diagnosis and targeted therapy.

Recent Advances in Cancer Therapeutic Copper-Based Nanomaterials for Antitumor Therapy.

Copper serves as a vital microelement which is widely present in the biosystem, functioning as multi-enzyme active site, including oxidative stress, lipid oxidation and energy metabolism, where oxidation and reduction characteristics are both beneficial and lethal to cells. Since tumor tissue has a higher demand for copper and is more susceptible to copper homeostasis, copper may modulate cancer cell survival through reactive oxygen species (ROS) excessive accumulation, proteasome inhibition and anti-angiogenesis. Therefore, intracellular copper has attracted great interest that multifunctional copper-based nanomaterials can be exploited in cancer diagnostics and antitumor therapy. Therefore, this review explains the potential mechanisms of copper-associated cell death and investigates the effectiveness of multifunctional copper-based biomaterials in the field of antitumor therapy.

Shape-Controlled Synthesis of Covalent Organic Frameworks Enabled by Polymerization-Induced Phase Separation.

The shape and morphology modulations of covalent organic frameworks (COFs) are both difficult, but are of significance to tackle to realize high-performance and practical applications. Here, a two-step method is reported that separates the phase separation and crystallization processes for the shape-controlled synthesis of COFs. The insight into the polymerization-induced phase separation (PIPS) allows for the flexible shaping of COFs into column, rod, film and others, as well as for constructing hierarchically porous structure. The as-synthesized COF monoliths are crack-free, no powder detaching, and show 214 MPa of compressive modulus. The resulting good permeability and mechanical flexibility enable COF films to apply for flow-through adsorption and extraction of pollutants at high flow rates. This work successfully resolves the contradiction between PIPS and crystallization, offering a general approach for scalable production of COFs with desired shapes, sizes, and morphologies.

Image-guided interstitial brachytherapy for recurrent cervical cancer after radiotherapy: A single institution experience.

Purpose: The aim of this study is to evaluate the efficacy and toxicity of image-guided high-dose rate (HDR) interstitial brachytherapy (ISBT) for the reirradiation of cervical cancer within a previously irradiated area. Methods and materials: Twenty-three consecutive patients with cervical cancer were reirradiated with curative intent using brachytherapy (BT) with or without external beam irradiation. The median biologically equivalent dose in 2-Gy fractions (EQD2) for reirradiation was 64.0 Gy (range: 31.3-95.1 Gy), and the median cumulative EQD2 (for primary treatment and reirradiation) was 152.4 Gy (range: 97.8-200.9 Gy). The average clinical target volume was 82.9 cm3 (range: 26.9-208.3 cm3), and the median treatment-free interval (TFI) was 13 months (range: 3-93 months). Results: The median follow-up time was 19 months (range: 2-59 months). The complete response rate after reirradiation was 56.5%. The 1-, 2- 3-, and 4-year post-relapse survival (PRS) rates were 65.2%, 43.5%, 33.8%, and 27.1%, respectively. The median reirradiation EQD2 D2cc of rectum and bladder was 39.5 Gy (range = 14.6-96.2 Gy) and 52.1 Gy (range = 29.1-114.2 Gy). The median cumulative EQD2 D2cc of rectum and bladder was 115.0 Gy (range = 84.4-189.3 Gy) and 130.5 Gy (range = 95.5-173.5 Gy). During follow-up, nine (39.1%) patients had experienced grade 3 or 4 late toxicities. Grade ≥3 rectal toxicity occurred in three patients (13.0%). Grade ≥3 urinary toxicity occurred in five patients (21.7%). One patient (4.3%) had both grade ≥3 urinary and rectal toxicity. Tumor volume, TFI, tumor invasion organ number, and local control were significant prognostic factors adversely affecting OS. Conclusions: For recurrent cervical cancer after radiotherapy, reirradiation of HDR-ISBT is feasible, even if the local tumor invasion is large, with a good chance of survival and acceptable side effects.

Prophylactic extended-field irradiation for locally advanced cervical cancer.

Concomitant chemoradiotherapy is the standard treatment for locally advanced cervical cancer. Pelvic irradiation is commonly recommended for patients with negative para-aortic lymph nodes(PALNs). However, owing to the development of imaging-guided brachytherapy, distant failure has become the main failure pattern. The PALNs are a vital site of distant metastasis, and the para-aortic region may contain occult microscopic metastases that are barely detected owing to imaging technology restriction. The prognostic of patients who experienced PALN failure is dismal. Typically, there are four ways to decrease PALN failure. First, surgical staging can be performed to assess the occurrence of metastasis in the para-aortic region; however, the application of surgical staging is decreasing owing to controversial survival benefits and accompanying complications of surgery. Second, regular imaging surveillance and timely salvage of early recurrences could reduce PALN failure. Third, better systemic adjuvant therapy could be recommended since it has enormous potential to reduce distant metastases and improve overall survival. Fourth, performing prophylactic extended-field irradiation (EFI), including pelvic and para-aortic region irradiation, can sterilize occult microscopic metastases in the para-aortic region and improve survival. Prior investigations have revealed that prophylactic EFI could reduce PALN failure as well as distant metastasis and present the benefit of survival. Yet, owing to the serious morbidity induced by enlarged irradiation field in the era of conventional irradiation techniques, further research on EFI is stagnated. Nowadays, with the development of new technologies, intensity modulated radiation therapy can deliver a higher dose to tumors with acceptable toxicity. Prophylactic EFI regained attention. However, the inclusion criteria of prophylactic EFI in existing studies reveal great discrepancies. Thus, it is urgent to precisely identify indications for better survival and lower complications in patients with cervical cancer. In this review, we identify indications and summary guidelines for prophylactic EFI, which may provide a foundation for further trials and clinical applications.

Multimodality treatment for multiple recurrences of cervical cancer after radiotherapy: a case report.

Background: Despite the availability of multiple treatments, the prognosis of recurrent cervical cancer (RCC) remains poor. There are no reports of the entire treatment of cases with multiple recurrences, and clinicians have no guidelines in such cases. We share our experience and consider this complex case of multiple recurrences of cervical cancer. Case Description: We report our encounter with a challenging case of locally advanced cervical cancer with multiple recurrences after primary chemoradiotherapy. The first recurrence was a bulky lesion invading the posterior bladder wall and pelvic wall accompanied by severe haematuria and moderate anaemia. The patient was treated with various treatments during the course of the disease, including pelvic exenteration (PE), external beam radiotherapy (EBRT), radioactive seed implantation, and targeted therapy. These salvage treatments led to an overall survival (OS) of 47 months, a progression-free survival (PFS) after the last chemotherapy of 34 months, and a post-relapse survival of 13.5 months. However, the patient died from severe infection due to an intestinal fistula. Conclusions: This study reports on the experience of treatment after multiple relapses to provide a reference for clinicians. It suggests that PE should be considered for cervical cancer patients with central recurrence within the primary irradiated field when positive margins can be guaranteed, but it can be palliative even if the pelvic wall is invaded when no other treatments are available. Appropriate extension of resection or additional treatments such as intraoperative radiotherapy (IORT) and neoadjuvant chemotherapy can be considered for patients at high risk of re-recurrence.

High-Performance NMHC Detection Enabled by a Perylene Bisimide-Cored Metallacycle Complex-Based Fluorescent Film Sensor.

Non-methane hydrocarbons (NMHCs) can serve as precursors of ozone and photochemical smog, and hence their highly efficient detection is of great importance for air quality monitoring. Here, we synthesized a new fluorescent perylene bisimide (PBI)-cored metallacycle complex through coordination-driven self-assembly and used it for the production of a fluorescent film sensor. The unique rectangular structure of the developed fluorophore endows the sensor with enhanced sensing performance and discriminability to n-alkanes (C5-10). Specifically, the experimental detection limits for n-pentane, n-hexane, and n-decane are 39, 7, and 1.4 mg/m3, respectively, and the corresponding linear ranges are from 39 to 2546, 7 to 1745, and 1.4 to 85 mg/m3, respectively. Moreover, the sensing is fully reversible. In tandem with a gas chromatographic separation system, the film sensor showed comparable detection ability for the n-alkanes with a commercial flame ionization detector (FID), while the film sensor needs no hydrogen; it occupies a much smaller size (30 × 30 × 44 mm3) and consumes less energy (0.215 W). Further studies demonstrated that the developed sensor can be used for on-site and real-time quantification of NHMCs, laying the foundation for developing into a portable detector.

Circular RNA: A potential diagnostic, prognostic, and therapeutic biomarker for human triple-negative breast cancer.

Triple-negative breast cancer (TNBC), which is the most malignant subtype of breast cancer (BC), accounts for 10%-20% of all BC cases. TNBC, which occurs more frequently in young women, is characterized by high rates of cell proliferation and metastasis and poor prognosis. Chemotherapy is the primary systemic therapeutic strategy for TNBC. However, chemotherapy is largely unsuccessful, and effective targeted therapies for TNBC have not been established. Therefore, it is a matter of great urgency to identify precise molecular targets for the promising prognosis of patients with TNBC. Circular RNAs (circRNAs), which are a type of non-coding RNAs (ncRNAs), are abundantly expressed in the eukaryotic cells and exhibit diverse cellular functions. The roles of circRNAs are to sponge microRNA or RNA-binding proteins, regulate gene expression, and serve as templates for translation. Here, we review the current findings on the potential of circRNAs as a diagnostic, prognostic, and therapeutic biomarker for TNBC. However, further studies are essential to elucidate the functions of circRNAs in TNBC. This review also discusses the current limitations and future directions of TNBC-associated circRNAs, which can facilitate the translation of experimental research into clinical application.

High-Performance Sensing of Formic Acid Vapor Enabled by a Newly Developed Nanofilm-Based Fluorescent Sensor.

Although it is widely used in industry and food products, formic acid can be dangerous owing to its corrosive properties. Accurate determination of formic acid would not only benefit its qualified uses but also be an effective way to avoid corrosion or injury from inhalation, swallowing, or touching. Herein, we present a nanofilm-based fluorescent sensor for formic acid vapor detection with a wide response range, fast response speed, and high sensitivity and selectivity. The nanofilm was synthesized at a humid air/dimethyl sulfoxide (DMSO) interface through dynamic covalent condensation between two typically designed building blocks, de-tert-butyl calix[4]arene-tetrahydrazide (CATH) and 4,4',4″,4‴-(ethene-1,1,2,2-tetrayl)tetra-benzaldehyde (ETBA). The as-prepared nanofilm is uniform, flexible, fluorescent, and photochemically stable. The thickness and fluorescence intensity of the nanofilm can be facilely adjusted by varying the concentration of the building blocks and the sensing performance of the nanofilm can be optimized accordingly. Based on the nanofilm, a fluorescent sensor with a wide response range (4.4 ppt-4400 ppm) for real-time and online detection of formic acid vapor was built. With the sensor, a trace amount (0.01%) of formic acid in petroleum ether (60-90 °C) can be detected within 3 s. Besides, fluorescence quenching of the nanofilm by formic acid vapor can be visualized. It is believed that the sensor based on the nanofilm would find real-life applications in corrosion and injury prevention from formic acid.

Insights into the mechanisms of Th17 differentiation and the Yin-Yang of Th17 cells in human diseases.

Th17 cells are a lineage of CD4+ T helper cells with Th17-specific transcription factors RORγt and RoRα. Since its discovery in 2005, research on Th17 has been in rapid progress, and increasing cytokines or transcription factors have been uncovered in the activation and differentiation of Th17 cells. Furthermore, growing evidence proves there are two different subsets of Th17 cells, namely non-pathogenic Th17 (non-pTh17) and pathogenic Th17 (pTh17), both of which play important roles in adaptive immunity, especially in host defenses, autoimmune diseases, and cancer. In this review, we summarize and discuss the mechanisms of Th17 cells differentiation, and their roles in immunity and diseases.

High-Performance Ketone Sensing in Vapor Phase Enabled by o-Carborane-Modified Cyclometalated Alkynyl-Gold(III) Complex-Based Fluorescent Films.

Development of high-performance, low-power-consumption, small-sized detectors is a key issue for fabricating specific miniaturized chromatographs (GCs). Herein, we report, for the first-time, utilization of a film-based fluorescent sensor as a GC detector. In the studies, we designed a new o-carborane derivative of a known cyclometalated alkynyl-gold(III) complex, Au-CB. Unlike the parent gold(III) complex, the newly synthesized Au-CB depicted a remarkable aggregation-induced emission (AIE) property, enabling fabrication of a fluorescent film. The film emission is highly sensitive to the presence of ketones such as acetone, 2-pentanone, 3-pentanone, cyclopentanone, etc., in the air. It was demonstrated that the sensing performance of the film could be further improved by changing the film from a planar structure to a tubular one. Via combination with an earlier reported homemade sensory device, a conceptual film-based fluorescent sensor was developed, which demonstrated instant and fully reversible response to the ketones. The experimental detection limits for cyclohexanone and acetone could be lower than 0.08 and 13.0 ppm, respectively. Moreover, the sensor is super stable, as 24 h continuous illumination resulted in less than 1.0% reduction of the fluorescence emission, 50 successive sensings showed no observable decay in the performance, and more than 1 year of storage had no effect upon the property. Further studies demonstrated that the film sensor could be used as a GC detector with performance comparable to the commercial flame ionization detector (FID), which lays the foundation for future applications in specific miniaturized GCs because of its merits in size, power consumption, carrier gas, etc.

Aristocratic human papillomavirus drove cervical cancer: a study of the therapeutic potential of the combination of interferon with zinc.

Human papillomavirus (HPV) infection is related to cancer growth of vaginal, cervical, vulva, penile, anogenital, and non-genital oropharyngeal sites. HPV, as a sexually transmitted virus, infects all sexes similarly but with more significant pathological risks in women. This accounts for high mortality due to late detection and poor prognosis. The initial development and eventual progress of this cancer type depend entirely on three main oncogenes E5, E6 and E7, constitutively expressed to lead to carcinogenesis. Despite an opportunity for pharmacological therapy, there is still a shortage of medical treatment that may remove HPV from infected lesions. This study offers a concise summary of the nature of the issue and the current status of work on potential lead molecules and therapeutic approaches that show the capacity of HPV therapies to counteract the roles of deregulation of E5, E6, and E7.