Iron retardation in lysosomes protects senescent cells from ferroptosis.

Ferroptosis, an iron-triggered modality of cellular death, has been reported to closely relate to human aging progression and aging-related diseases. However, the involvement of ferroptosis in the development and maintenance of senescent cells still remains elusive. Here, we established a doxorubicin-induced senescent HSkM cell model and found that both iron accumulation and lipid peroxidation increase in senescent cells. Moreover, such iron overload in senescent cells has changed the expression panel of the ferroptosis-response proteins. Interestingly, the iron accumulation and lipid peroxidation does not trigger ferroptosis-induced cell death. Oppositely, senescent cells manifest resistance to the ferroptosis inducers, compared to the proliferating cells. To further investigate the mechanism of ferroptosis-resistance for senescent cells, we traced the iron flux in cell and found iron arrested in lysosome. Moreover, disruption of lysosome functions by chloroquine and LLOMe dramatically triggered the senescent cell death. Besides, the ferroitinophagy-related proteins FTH1/FTL and NCOA4 knockdown also increases the senescent cell death. Thus, we speculated that iron retardation in lysosome of senescent cells is the key mechanism for ferroptosis resistance. And the lysosome is a promising target for senolytic drugs to selectively clear senescent cells and alleviate the aging related diseases.

The Impact of New Regulations on Prevention and Control of E-Cigarettes on Adolescents in Middle Schools - A City in China, 2022-2023.

What is already known about this topic?: To protect the health of young people from the harmful impacts of electronic cigarettes (e-cigarettes), China has enacted various policies and regulations since 2018. As of October 1, 2022, the Electronic Cigarette Management Measures were put into action. They prohibited the sale of flavored e-cigarettes, permitting only those of plain tobacco flavor to be sold. What is added by this report?: The illegal market for flavored e-cigarettes, often disguised as milk tea cups, cola cans, and violent bear images, continues to flourish. There is an increased need to bolster support for the prohibition of flavored e-cigarettes and enhance public awareness of associated regulations. What are the implications for public health practice?: To advance the health of China's youth, it is crucial to improve the implementation and understanding of e-cigarette policies and guidelines.

Biomimetic Nano-Cancer Stem Cell Scavenger for Inhibition of Breast Cancer Recurrence and Metastasis after FLASH-Radiotherapy.

Compared to conventional radiotherapy (RT), FLASH-RT delivers ultra-high dose radiation, significantly reducing damage to normal tissue while guaranteeing the effect of cancer treatment. However, cancer recurrence and metastasis frequently occur after all RT due to the existence of intractable cancer stem cells (CSCs). To address this, a biomimetic nanoplatform (named TAFL) of tumor-derived exosome fusion liposomes is designed by co-loading aggregation-induced emission photothermal agents, TPE-BBT, and anti-cancer drugs, aspirin, aiming to clear CSCs for inhibiting cancer recurrence and metastasis after FLASH-RT therapy . Aspirin released in TAFL system triggered by laser irradiation can induce apoptosis and DNA damage of 4T1 CSCs, comprehensively downregulate their stemness phenotype, and inhibit their sphericity. Furthermore, the TPE-BBT mediated mild-photothermal therapy can alleviate the hypoxic tumor microenvironment, inhibit the DNA repair of CSCs, which further amplifies the effect of aspirin against CSCs, therefore reduces the effective dose of aspirin, making TAFL more biologically safe. In vivo experimental results demonstrated that decreased CSCs population mediated by TAFL system treatment significantly inhibited tumor recurrence and metastasis after FLASH-RT therapy. In summary, this TAFL system   provides a new idea for the future clinical application of FLASH-RT therapy.

A latent profile analysis of resilience and their relation to differences in sleep quality in patients with lung cancer.

PURPOSE: Sleep problems are a significant issue in patients with lung cancer, and resilience is a closely related factor. However, few studies have identified subgroups of resilience and their relationship with sleep quality. This study aimed to investigate whether there are different profiles of resilience in patients with lung cancer, to determine the sociodemographic characteristics of each subgroup, and to determine the relationship between resilience and sleep quality in different subgroups. METHODS: A total of 303 patients with lung cancer from four tertiary hospitals in China completed the General Sociodemographic sheet, the Connor-Davidson Resilience Scale, and the Pittsburgh Sleep Quality Index. Latent profile analysis was applied to explore the latent profiles of resilience. Multivariate logistic regression was used to analyze the sociodemographic variables in each profile, and ANOVA was used to explore the relationships between resilience profiles and sleep quality. RESULTS: The following three latent profiles were identified: the "high-resilience group" (30.2%), the "moderate-resilience group" (46.0%), and the "low-resilience group" (23.8%). Gender, place of residence, and average monthly household income significantly influenced the distribution of resilience in patients with lung cancer. CONCLUSION: The resilience patterns of patients with lung cancer varied. It is suggested that health care providers screen out various types of patients with multiple levels of resilience and pay more attention to female, rural, and poor patients. Additionally, individual differences in resilience may provide an actionable means for addressing sleep problems.

Copper-Based Single-Atom Nanozyme System Mimicking Platelet Cells for Enhancing the Outcome of Radioimmunotherapy.

Background: Radiotherapy is an indispensable part of the multidisciplinary treatment of breast cancer (BC). Due to the potential for serious side effects from ionizing radiation in the treatment of breast cancer, which can adversely affect the patient's quality of life, the radiation dose is often limited. This limitation can result in an incomplete eradication of tumors. Methods: In this study, biomimetic copper single-atom catalysts (platelet cell membrane camouflaging, PC) were synthesized with the aim of improving the therapeutic outcomes of radiotherapy for BC. Following guidance to the tumor site facilitated by the platelet cell membrane coating, PC releases a copper single-atom nanozyme (SAzyme). This SAzyme enhances therapeutic effects by generating reactive oxygen species from H2O2 and concurrently inhibiting the self-repair mechanisms of cancer cells through the consumption of intracellular glutathione (GSH) within the tumor microenvironment. PC-augmented radiotherapy induces immunogenic cell death, which triggers an immune response to eradicate tumors. Results: With the excellent biocompatibility, PC exhibited precise tumor-targeting capabilities. Furthermore, when employed in conjunction with radiotherapy, PC showed impressive tumor elimination results through immunological activation. Remarkably, the tumor suppression rate achieved with PC-enhanced radiotherapy reached an impressive 93.6%. Conclusion: Therefore, PC presents an innovative approach for designing radiosensitizers with tumor-specific targeting capabilities, aiming to enhance the therapeutic impact of radiotherapy on BC.

The effects of physical symptoms, self-efficacy and social constraints on fear of cancer recurrence in breast cancer survivors: Examining the mediating role of illness representations.

OBJECTIVE: Fear of cancer recurrence (FCR) is common in breast cancer survivors (BCS). This study examined the mediating role of illness representations in the relationships between FCR and physical symptoms, social constraint and self-care self-efficacy. METHODS: In this cross-sectional study, 385 women with breast cancer completed a series of questionnaires including the FCR Inventory, Social Constraints Scale-15, Cancer Survivors Self-Efficacy Scale, Illness Perception Questionnaire-Revised and European Organization for Research and Treatment Quality of Life Questionnaire-Breast Cancer. Structural equation modelling method was conduct by using a bootstrapping method. RESULTS: Physical symptoms (ß = 0.272, p < 0.01), social constraints (ß = 0.130, p < 0.01), self-efficacy (ß = -0.233, p < 0.01) and illness representation (ß = 0.261, p < 0.01) have direct effects on FCR. The indirect effects of physical symptoms (ß = 0.10, p < 0.01), social constraints (ß = 0.076, p < 0.01) and self-efficacy (ß = -0.025, p < 0.05) on FCR were partially mediated by illness representations. CONCLUSIONS: In this study, the effects of physical symptoms, social constraints and self-efficacy on FCR were found to be mediated by illness representation. Reducing the impact of negative illness representations on FCR by reducing physical symptoms, increasing self-efficacy, and promoting open disclosure of cancer-related concerns may be effective in reducing FCR in BCS.

Two-dimensional multifunctional nanosheets as radiosensitizers for chemodynamic/radio-therapy.

The hypoxia tumor microenvironment and low radiation attenuation coefficient of tumor tissue usually limit the efficiency of radiotherapy. In this study, a two-dimensional multifunctional nano-sensitizer, CuNS@Pt, was prepared to function as a radiosensitizer, enhancing radiotherapy through multiple mechanisms. Numerous active sites were provided for the deposition of X-ray radiation energy by the in-situ chemical reduction of Pt to create functional hybrids on Cu-based nanosheets. CuNS@Pt catalyzed high concentration of endogenous hydrogen peroxide to generate oxygen in tumor microenvironment, alleviating the physiological environment of hypoxic tumors. Additionally, CuNS could reduce the content of intrinsic glutathione (GSH) and catalyze hydrogen peroxide to form hydroxyl radicals (·OH). The generated ·OH could damage mitochondria and destroy redox homeostasis due to the functional inclusion of Cu species, thereby achieving chemodynamic therapy and further improving the radiation effect. Both in vivo and in vitro experiments showed that the nano sensitizer effectively improved the therapeutic efficiency of radiotherapy and had good biological safety. All in all, this study provides a pragmatic and doable platform for maximizing the efficacy of RT in cancer. This study also highlights the future research value of two-dimensional nanomaterials.

[Early prediction of severe COVID-19 in patients with Sjögren's syndrome].

OBJECTIVE: To investigate the predictive value of blood cell ratios and inflammatory markers for adverse prognosis in patients with primary Sjögren's syndrome (PSS) combined with coronavirus disease 2019 (COVID-19). METHODS: We retrospectively collected clinical data from 80 patients with PSS and COVID-19 who visited the Rheumatology and Immunology Department of the First Affiliated Hospital of Nanchang University from December 2022 to February 2023. Inclusion criteria were (1) meeting the American College of Rheumatology (ACR) classification criteria for Sjögren's syndrome; (2) confirmed diagnosis of COVID-19 by real-time reverse transcription polymerase chain reaction or antigen testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); (3) availability of necessary clinical data; (4) age > 18 years. According to the clinical classification criteria of the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (trial the 10th Revised Edition)", the patients were divided into the mild and severe groups. Disease activity in primary Sjögren' s syndrome was assessed using the European League Against Rheumatism (EULAR) Sjögren' s syndrome disease activity index (ESSDAI). Platelet-lymphocyte ratio (PLR), C-reactive protein-lymphocyte ratio (CLR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and other laboratory data were compared between the two groups within 24-72 hours post-infection. RESULTS: The mild group consisted of 66 cases with an average age of (51. 52±13. 16) years, and the severe group consisted of 14 cases with an average age of (52.64±10.20) years. Disease activity, CRP, platelets, PLR, and CLR were significantly higher in the severe group compared with the mild group (P < 0.05). Univariate analysis using age, disease activity, CRP, platelets, PLR, and CLR as independent variables indicated that disease activity, CRP, PLR, and CLR were correlated with the severity of COVID-19 (P < 0.05). Multivariate logistic regression analysis further confirmed that PLR (OR=1.016, P < 0.05) and CLR (OR=1.504, P < 0.05) were independent risk factors for the severity of COVID-19 in the critically ill patients. Receiver operator characteristic (ROC) curve analysis showed that the area under the curve (AUC) for PLR and CLR was 0.708 (95%CI: 0.588-0.828) and 0.725 (95%CI: 0.578-0.871), respectively. The sensitivity for PLR and CLR was 0.429 and 0.803, respectively, while the highest specificity was 0.714 and 0.758, respectively. The optimal cutoff values for PLR and CLR were 166.214 and 0.870, respectively. CONCLUSION: PLR and CLR, particularly the latter, may serve as simple and effective indicators for predicting the prognosis of patients with PSS and COVID-19.

Multifunctional AuPt Nanoparticles for Synergistic Photothermal and Radiation Therapy.

Background: Photothermal therapy (PTT) has gained considerable interest as an emerging modality for cancer treatment in recent years. Radiation therapy (RT) has been widely used in the clinic as a traditional treatment method. However, RT and PTT treatments are limited by side effects and penetration depth, respectively. In addition, hypoxia within the tumor can lead to increased resistance to treatment. Methods: We synthesized multiple sizes of AuPt by modulating the reaction conditions. The smallest size of AuPt was selected and modified with folic acid (FA) for PTT and RT synergy therapy. Various methods including transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FITR) are used to determine the structure and composition of AuPt-FA (AF). In addition, we researched the photothermal properties of AF with IR cameras and infrared lasers. Flow cytometry, colony formation assays, CCK8, and fluorescent staining for probing the treatment effect in vitro. Also, we explored the targeting of AF by TEM and In Vivo Imaging Systems (IVIS). In vivo experiments, we record changes in tumor volume and weight as well as staining of tumor sections (ROS, Ki67, and hematoxylin and eosin). Results: The AuPt with particle size of 16 nm endows it with remarkably high photothermal conversion efficiency (46.84%) and catalase activity compared to other sizes of AuPt (30 nm and 100 nm). AF alleviates hypoxia in the tumor microenvironment, leading to the production of more reactive oxygen species (ROS) during the treatment. In addition, the therapeutic effect was significantly enhanced by combining RT and PTT, with an apoptosis rate of 81.1% in vitro and an in vivo tumor volume reduction rate of 94.0% in vivo. Conclusion: These results demonstrate that AF potentiates the synergistic effect of PTT and RT and has the potential for clinical translation.

[Research and application of intelligent hyperspectral analysis technology for Chinese materia medica].

With the development of imaging technology and artificial intelligence, hyperspectral imaging technology provides a fast, non-destructive, intelligent, and precise new method for the analysis of Chinese materia medica(CMM). This paper summarized the methods and applications of hyperspectral imaging technology combined with intelligent analysis technology in the field of CMM in recent years, focusing on the acquisition and preprocessing of hyperspectral data, intelligent analysis methods of hyperspectral data, and practical cases of these technologies in the field of CMM. Hyperspectral data of CMM can provide spectral information with nanometer-level resolution and rich spatial texture information simultaneously. This paper summarized the acquisition process, including black-and-white board calibration and region-of-interest extraction, and preprocessing methods including smoothing, differentiation, scale-space, and scattering correction. The feature extraction methods in terms of spectral, spatial, color, and texture were briefly described, and common modeling methods were summarized. Finally, this paper reviewed the research cases of the application of the above methods to the fields of CMM, such as authenticity identification, origin tracing, variety recognition, year identification, sulfur fumigation degree determination, and quantitative measurement.

Mini-dose methotrexate combined with methylprednisolone as a first-line treatment for acute graft-versus-host disease: A phase 2 trial.

Background and Objectives: Acute graft-versus-host disease (aGvHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methylprednisolone (MP; 1-2 mg/kg/day) remains the standard first-line therapy for aGvHD, although no response is detected in nearly one-half of the patients with aGvHD. This study aimed to investigate the feasibility of mini-dose methotrexate (MTX) combined with standard-dose MP as a front-line therapy for aGvHD. Materials and Methods: A prospective Phase 2 clinical trial was performed to evaluate the safety and efficacy of 5 mg/m2 MTX combined with 1 mg/kg/day MP as the initial therapy in 31 patients with aGvHD. Moreover, the effects of MTX combined with MP were explored in a humanized xenogeneic murine model of aGvHD. Results: The overall response and complete response rate at 7 days after the initial treatment were 100% and 83%, respectively. The overall response rate on day 28 was 87%. The complete response rates for aGvHD grades I, II, and III were 100% (6/6), 82% (18/22), and 66% (2/3), respectively. Grade 3 toxicities occurred in only three patients presenting with cytopenia. Importantly, MTX and MP demonstrated synergistic effects on ameliorating aGvHD in humanized xenogeneic murine model. Conclusion: The current study suggests that mini-dose MTX combined with standard-dose MP could potentially become a novel first-line therapy for patients with aGvHD.

Core-shell silica@CuxZnAl LDH catalysts for efficient CO2 hydrogenation to methanol.

The efficient production of methanol by reduction of CO2 using green hydrogen is a promising strategy from both a green chemistry and a carbon net zero perspective. Herein, we report the synthesis of well-dispersed core-shell catalyst precursors using silica@CuxZnAl-LDHs that can convert CO2 to methanol. The catalyst precursors can be formed using either a commercially available silica (ES757) or a mesoporous silica (e.g. MCM-48). These hybrid materials show significantly enhanced catalytic performance compared to the equivalent unsupported CuxZnAl LDH precursor. Space-time yields of up to 0.7 gMeOH gcat-1 h-1 under mild operating conditions were observed.

Photothermal-Triggered Sulfur Oxide Gas Therapy Augments Type I Photodynamic Therapy for Potentiating Cancer Stem Cell Ablation and Inhibiting Radioresistant Tumor Recurrence.

Despite advances in cancer therapy, the existence of self-renewing cancer stem cells (CSC) can lead to tumor recurrence and radiation resistance, resulting in treatment failure and high mortality in patients. To address this issue, a near-infrared (NIR) laser-induced synergistic therapeutic platform has been developed by incorporating aggregation-induced emission (AIE)-active phototheranostic agents and sulfur dioxide (SO2 ) prodrug into a biocompatible hydrogel, namely TBH, to suppress malignant CSC growth. Outstanding hydroxyl radical (·OH) generation and photothermal effect of the AIE phototheranostic agent actualizes Type I photodynamic therapy (PDT) and photothermal therapy through 660 nm NIR laser irradiation. Meanwhile, a large amount of SO2 is released from the SO2 prodrug in thermo-sensitive TBH gel, which depletes upregulated glutathione in CSC and consequentially promotes ·OH generation for PDT enhancement. Thus, the resulting TBH hydrogel can diminish CSC under 660 nm laser irradiation and finally restrain tumor recurrence after radiotherapy (RT). In comparison, the tumor in the mice that were only treated with RT relapsed rapidly. These findings reveal a double-boosting ·OH generation protocol, and the synergistic combination of AIE-mediated PDT and gas therapy provides a novel strategy for inhibiting CSC growth and cancer recurrence after RT, which presents great potential for clinical treatment.

Supportive care needs of breast cancer survivors with different levels of fear of cancer recurrence: A cross-sectional survey study.

PURPOSE: To examine the supportive care needs of breast cancer survivors with nonclinical, subclinical, or clinical fear of cancer recurrence. METHODS: In this cross-sectional study, 385 breast cancer survivors consented and completed a set of online questionnaires. Supportive care needs were assessed by using the 34-item Supportive Care Needs Survey. Fear of cancer recurrence was assessed by using the Fear of Cancer Recurrence Inventory. RESULTS: One hundred eighty-four (47.8%) participants reported nonclinical fear of cancer recurrence, 147 (38.2%) reported subclinical fear of cancer recurrence, and 54 (14.0%) reported clinical fear of cancer recurrence. Higher levels of fear of cancer recurrence were associated with higher levels of supportive care needs in five domains (ß = 0.30-0.60, P < 0.001) after adjusting for places of residence, education, motherhood, and time since diagnosis. Among participants with nonclinical fears of cancer recurrence, the most common needs were in the 'Health care system/Information' domain (50.5%). Among participants with subclinical or clinical fear of cancer recurrence, the most common needs were in the 'Psychological' domain (85.7% and 96.3%, respectively). CONCLUSION: Fear of cancer recurrence was associated with supportive care needs. The most common needs among participants with subclinical or clinical fears of cancer recurrence were psychological needs.

Gold nanoparticle doped Cuhemin nanosheets with a remodeling tumor microenvironment for multiple radiotherapy sensitization.

Effective radiosensitizers are urgently needed due to the serious negative effects that high radiation doses might have. We created an integrated nano-system (Cuhemin-Au) made of Cuhemin nanosheets and Au nanoparticles (Au NPs) for sensitizing radiotherapy to solve this issue. This system can manifest enzyme-like activities to universally suppress the resistance pathways in breast cancer cells for amplifying radiation damage. Cuhemin-Au NPs increase the energy deposition of radiation owing to the high X-ray attenuation coefficient of Au. In addition, Cuhemin-Au has peroxidase (POD)-like and glucose oxidase (Gox)-like activity, and can also consume intracellular GSH, which can reduce intracellular GSH levels to reduce tumor cells' capacity to repair DNA and deplete intracellular glucose via their characteristic Gox-like catalytic activities, which can cause an increase in the oxidative stress and further produce H2O2. Cuhemin-Au then produced ˙OH, which upsets redox equilibrium and destroys mitochondria, leading to radiation sensitivity, after reacting with enough hydrogen peroxide in tumor cells. Cuhemin-Au combined with low dose RT (4 Gy) could significantly limit tumor development with fewer adverse effects, according to in vivo and in vitro experiments. This platform generated a fresh concept for the construction of a radiotherapy sensitization system and accomplished synergistic radiotherapy sensitization.

Type-I AIE Photosensitizer Loaded Biomimetic System Boosting Cuproptosis to Inhibit Breast Cancer Metastasis and Rechallenge.

Cuproptosis shows good application prospects in tumor therapy. However, the copper efflux mechanism and highly expressed intracellular reducing substances can inhibit the cuproptosis effects. In this study, a platelet vesicle (PV) coated cuprous oxide nanoparticle (Cu2O)/TBP-2 cuproptosis sensitization system (PTC) was constructed for multiple induction of tumor cuproptosis. PTC was prepared by physical extrusion of AIE photosensitizer (TBP-2), Cu2O, and PV. After the biomimetic modification, PTC can enhance its long-term blood circulation and tumor targeting ability. Subsequently, PTC was rapidly degraded to release copper ions under acid conditions and hydrogen peroxides in tumor cells. Then, under light irradiation, TBP-2 quickly enters the cell membrane and generates hydroxyl radicals to consume glutathione and inhibit copper efflux. Accumulated copper can cause lipoylated protein aggregation and iron-sulfur protein loss, which result in proteotoxic stress and ultimately cuproptosis. PTC treatment can target and induce cuproptosis in tumor cells in vitro and in vivo, significantly inhibit lung metastasis of breast cancer, increase the number of central memory T cells in peripheral blood, and prevent tumor rechallenge. It provides an idea for the design of nanomedicine based on cuproptosis.

Effectiveness of mindfulness-based interventions on anxiety, depression, and fatigue in people with lung cancer: A systematic review and meta-analysis.

BACKGROUND: Lung cancer is one of the most common cancers and poses a physical and psychological threat to patients. Mindfulness-based interventions are emerging forms of psychotherapy that are effective in improving physical and psychological symptoms, but no review has summarized their effectiveness on anxiety, depression, and fatigue in people with lung cancer. OBJECTIVES: To evaluate the effectiveness of mindfulness-based interventions in reducing anxiety, depression, and fatigue in people with lung cancer. DESIGN: Systematic review and meta-analysis. METHODS: We searched the PubMed, Web of Science, Embase, China Biology Medicine disc, Wanfang Data, China National Knowledge Infrastructure, and China Science and Technology Journal databases from inception to 13 April 2022. Eligible studies included randomized controlled trials of people with lung cancer receiving mindfulness-based interventions reporting on the outcomes of anxiety, depression, and fatigue. Two researchers independently reviewed the abstracts and full texts, extracted the data and assessed the risk of bias independently by using the Cochrane 'Risk of bias assessment tool'. The meta-analysis was performed by using Review Manager 5.4, and the effect size was calculated by the standardized mean difference and its 95% confidence interval. RESULTS: The systematic review included 25 studies (2420 participants), whereas the meta-analysis included 18 studies (1731 participants). Mindfulness-based interventions significantly decreased levels of anxiety [standardized mean difference = -1.15, 95% confidence interval (-1.36, -0.94), Z = 10.75, P < 0.001], depression [standardized mean difference = -1.04, 95% confidence interval (-1.60, -0.48), Z = 3.66, P < 0.001], and fatigue [standardized mean difference = -1.29, 95% confidence interval (-1.66, -0.91), Z = 6.79, P < 0.001]. The subgroup analysis indicated that programs lasting less than eight weeks in length with structured intervention components (e.g., mindfulness-based stress reduction and mindfulness-based cognitive therapy) and 45 min of daily home practice implemented in patients with advanced stage lung cancer showed better effects than programs lasting more than eight weeks in length with less structured components and more than 45 min of daily home practice implemented in patients with mixed stage lung cancer. The overall quality of the evidence was low due to the lack of allocation concealment and blinding and the high risk of bias in most studies (80%). CONCLUSIONS: Mindfulness-based interventions might be effective in reducing anxiety, depression, and fatigue in people with lung cancer. However, we cannot draw definitive conclusions because the overall quality of the evidence was low. More rigorous studies are needed to confirm the effectiveness and examine which intervention components may be most effective for improved outcomes.

A type I AIE photosensitiser-loaded biomimetic nanosystem allowing precise depletion of cancer stem cells and prevention of cancer recurrence after radiotherapy.

Radioresistance of Cancer stem cell (CSC) is an important cause of tumor recurrence after radiotherapy (RT). Herein, we designed a type I aggregation-induced emission (AIE) photosensitiser-loaded biomimetic mesoporous organosilicon nanosystem (PMT) for precise depletion of CSC to prevent tumor recurrence after RT. This PMT system is composed of a type I AIE photosensitiser (TBP-2) loaded mesoporous organosilicon nanoparticles (MON) with an outer platelet membrane. The PMT system is able to specifically target CSC. Intracellular glutathione activity leads to MON degradation and the release of TBP-2. Type I photodynamic therapy is activated by exposure to white light, producing a large amount of hydroxyl radicals to promote CSC death. The results of in vivo experiments demonstrated specific removal of CSC following PMT treatment, with no tumor recurrence observed when combined with RT. However, tumor recurrence was observed in mice that received RT only. The expression of CSC markers was significantly reduced following PMT treatment. We demonstrate the development of a system for the precise removal of CSC with good biosafety and high potential for clinical translation. We believe the PMT nanosystem represents a novel idea in the prevention of tumor recurrence.

Hsa_circ_0001550 impairs decidualization by regulating the proliferation and apoptosis of endometrial stromal cells.

RESEARCH QUESTION: What is the molecular function of hsa_circ_0001550 in decidualization? DESIGN: Human endometrial stromal cells (HESC) were isolated from the endometrium tissues to build an in-vitro decidualization model. Different concentrations of medroxyprogesterone acetate (MPA) were used to observe whether the expression level of hsa_circ_0001550 was related to progesterone. Biological characteristics and distribution of hsa_circ_0001550 were determined by RNase R, actinomycin D (Act D) assay and cytoplasmic/nuclear fraction assay. Then the overexpression of hsa_circ_0001550 was achieved by adenovirus vector. Cell proliferation was determined by Cell Counting Kit-8 (CCK-8) assays. The cell cycle was assessed by flow cytometry analyses. Cell apoptosis was determined by annexin-V/propidium iodide double staining experiment and western blotting. RESULTS: The expression of hsa_circ_0001550 was decreased in decidua and decidualized HESC (P < 0.001, P = 0.014). Hsa_circ_0001550 is a covalently closed RNA molecule that was verified by RNase R assay and Act D assay (P = 0.012). Nuclear and cytoplasmic separation experiments confirmed that hsa_circ_0001550 was mainly distributed in the cytoplasm. Overexpression of hsa_circ_0001550 inhibited decidualization of HESC (P < 0.0001). Furthermore, overexpression of hsa_circ_0001550 inhibited proliferation by decreasing the number of S phase cells (P = 0.033). Annexin-V/propidium iodide double staining experiment and western blotting revealed that overexpression of hsa_circ_0001550 promoted HESC apoptosis (P < 0.001, P = 0.0139). CONCLUSIONS: Hsa_circ_0001550 impairs decidualization of HESC. Progesterone decreases the expression of hsa_circ_0001550. The results may provide new insights into the cause of decidualization.

Hydrogel co-loading SO2 prodrug and FeGA nanoparticles for enhancing chemodynamic therapy by photothermal-triggered SO2 gas therapy.

Chemodynamic therapy (CDT) is an effective anti-tumor method, while CDT alone cannot achieve a good therapeutic effect. Moreover, the overexpression of glutathione (GSH) in tumor cells dramatically limits the efficiency of CDT. Here, we proposed a hydrogel co-loading SO2 prodrug and FeGA nanoparticles (NPs) for enhancing CDT by photothermal-triggered SO2 gas therapy (FBH) system by mixing benzothiazolyl sulfonates (BTS) and FeGA NPs in a certain ratio and encapsulating them in a heat-sensitive hydrogel. FeGA NPs could accelerate the release of Fe2+ under acidic conditions and light, and combine with excess H2O2 in the tumor for chemokinetic treatment. BTS, as a water-soluble prodrug of SO2, can accurately control the release of SO2 gas by virtue of the excellent photothermal conversion ability of FeGA NPs and the acidic pH value of tumor site. SO2 can not only induce cell apoptosis, but also consume excess GSH in cancer cells and increase the content of reactive oxygen species, which seriously destroyed the redox balance in cancer cells and further promotes the therapeutic effect of Fenton reaction. The intelligent FBH system provided a new approach for the synergistic treatment of CDT and SO2 gas, which demonstrated good anticancer effects both in vivo and in vitro.