Fe-doped carbon dots: a novel biocompatible nanoplatform for multi-level cancer therapy.

BACKGROUND: Tumor treatment still remains a clinical challenge, requiring the development of biocompatible and efficient anti-tumor nanodrugs. Carbon dots (CDs) has become promising nanomedicines for cancer therapy due to its low cytotoxicity and easy customization. RESULTS: Herein, we introduced a novel type of "green" nanodrug for multi-level cancer therapy utilizing Fe-doped carbon dots (Fe-CDs) derived from iron nutrient supplement. With no requirement for target moieties or external stimuli, the sole intravenous administration of Fe-CDs demonstrated unexpected anti-tumor activity, completely suppressing tumor growth in mice. Continuous administration of Fe-CDs for several weeks showed no toxic effects in vivo, highlighting its exceptional biocompatibility. The as-synthesized Fe-CDs could selectively induce tumor cells apoptosis by BAX/Caspase 9/Caspase 3/PARP signal pathways and activate antitumoral macrophages by inhibiting the IL-10/Arg-1 axis, contributing to its significant tumor immunotherapy effect. Additionally, the epithelial-mesenchymal transition (EMT) process was inhibited under the treatment of Fe-CDs by MAPK/Snail pathways, indicating the capacity of Fe-CDs to inhibit tumor recurrence and metastasis. CONCLUSIONS: A three-level tumor treatment strategy from direct killing to activating immunity to inhibiting metastasis was achieved based on "green" Fe-CDs. Our findings reveal the broad clinical potential of Fe-CDs as a novel candidate for anti-tumor nanodrugs and nanoplatform.

Assessment of the internal and external exposure risks to methylsiloxanes in communities near a petroleum refinery.

Methylsiloxanes (MSs) are widely used in industrial production and have attracted much attention due to their potential health risks to humans. MSs are present in emissions from petroleum refining, and it is therefore important to assess the health risks to residents living near refineries. In this study, we evaluated the pollution characteristics and human exposure risks of three cyclic MS (CMS) oligomers (D4-D6) in areas upwind and downwind of a petroleum refinery. The concentrations of total CMSs were 4-33 times higher in the downwind than upwind areas. At the same sampling site, the concentrations of CMSs were higher indoors than outdoors. The maximum concentration of CMSs was found in the indoor environment 200 m downwind of the petroleum refinery (75 µg/m3 in air and 2.3 µg/g in dust). The concentrations and detection rates of CMSs in plasma samples were higher in the downwind than upwind residents. Although residents living downwind of the petroleum refinery were a non-occupationally exposed population, they should be considered a highly CMS-exposed population because of their extremely high internal exposure doses. Inhalation exposure was the main source of CMSs in the plasma of these residents. When different exposure pathways were investigated, inhalation exposure was the major contributor to the average daily dose in residents of locations near the petroleum refinery, whereas the dermal absorption of personal care products was the major contributor at other sites. Although the overall risks of exposure to total CMSs were below the chronic reference dose for all exposure pathways, the combined joint toxic effects of various CMSs remain unclear. Further studies are therefore required to determine the exposure risks and subsequent health effects of CMSs for the residents of these areas.

Ferroptosis: The Entanglement between Traditional Drugs and Nanodrugs in Tumor Therapy.

Ferroptosis is a non-apoptotic programmed cell death caused by the accumulation of lipid peroxide. System Xc-/glutathione peroxidase 4 (GPX4) axis and iron axis are two main pathways regulating ferroptosis. Simultaneously, multiple pathways are also involved in the ferroptosis regulation. Ferroptosis is an intense area of the current study. With the improvement of the regulatory mechanisms that underlie ferroptosis, a variety of drugs associated with ferroptosis have been discovered and developed for cancer therapy. Among them, traditional drugs were developed initially. Small molecule compounds that regulate ferroptosis signaling pathway and iron complexes that promote the Fenton reaction have become important drugs for inducing ferroptosis. In recent years, the emerging development of nanotechnology has promoted the research of ferroptosis nanodrugs. Iron-based nanomaterials are extensively tested as ferroptosis-inducing agents. Furthermore, nanoscale drug delivery systems offer a suitable scaffold for traditional drug therapies. Traditional drugs and nanodrugs are complementary, each with their own strengths and limitations. This review describes the latest studies on the regulation of ferroptosis in tumor cells and focuses on the entanglement between traditional drugs and nanodrugs. To conclude, the challenges and perspectives in this field are put forward.

Probiotics protect against hepatic steatosis in tris (2-chloroethyl) phosphate-induced metabolic disorder of mice via FXR signaling.

Tris (2-chloroethyl) phosphate (TCEP), the most widely useful and most frequently detective organophosphate flame retardants in environment, has been shown potential relationship with adolescent weight. Probiotics is an effective therapy for metabolic diseases such as obesity and NAFLD with gut microbiota dysregulation. This study aims to explore the protective effects of probiotics against lipid metabolic disorder induced by chronic TCEP exposure and demonstrate the mechanism of this event. The data showed that dietary complex probiotics supplement attenuated TCEP-induced obesity, hyperlipidemia, liver dysfunction, and hepatic steatosis. In addition, dietary complex probiotics suppressed TCEP-promoted ileal FXR signaling, and upregulated hepatic FXR/SHP pathway inhibited by TCEP. Moreover, dietary complex probiotics stimulated PPARα-mediated lipid oxidation and suppressed SREBP1c/PPARγ-mediated lipid synthesis via regulation of FXR signaling. Therefore, this study indicates that dietary complex probiotics could protect against hepatic steatosis via FXR-mediated signaling pathway in TCEP-induced metabolism disorder in mice, resulting in attenuation of systemic lipid accumulation.

A prophylactic effect of aluminium-based adjuvants against respiratory viruses via priming local innate immunity.

Infection caused by respiratory viruses can lead to a severe respiratory disease and even death. Vaccination is the most effective way to prevent the disease, but it cannot be quickly applied when facing an emerging infectious disease. Here, we demonstrated that immunization with an aluminium-zinc hybrid particulate adjuvant (FH-001) alone, bearing great resemblance in morphology with commonly used aluminium-based adjuvants in vaccines, could quickly induce mice to generate a broadly protective immune response to resist the lethal challenge of influenza B viruses. Furthermore, a multi-omics-based analysis revealed that the alveolar macrophage and type I interferon pathway, rather than adaptive immunity and type II interferon pathway, were essential for the observed prophylactic effect of FH-001. More importantly, a similar protective effect was observed against influenza A virus strain A/Shanghai/02/2013(H7N9), A/California/04/2009(H1N1) and respiratory syncytial virus. Therefore, we introduced here a new and promising strategy that can be quickly applied during the outbreak of emerging respiratory viruses.

CAR T­cell therapy for gastric cancer: Potential and perspective (Review).

Gastric cancer (GC) is one of the most frequently diagnosed digestive malignancies and is the third leading cause of cancer­associated death worldwide. Delayed diagnosis and poor prognosis indicate the urgent need for new therapeutic strategies. The success of chimeric antigen receptor (CAR) T­cell therapy for chemotherapy­refractory hematological malignancies has inspired the development of a similar strategy for GC treatment. Although using CAR T­cells against GC is not without difficulty, results from preclinical studies remain encouraging. The current review summarizes relevant preclinical studies and ongoing clinical trials for the use of CAR T­cells for GC treatment and investigates possible toxicities, as well as current clinical experiences and emerging approaches. With a deeper understanding of the tumor microenvironment, novel target epitopes and scientific­technical progress, the potential of CAR T­cell therapy for GC is anticipated in the near future.

Combination of PEG-decorated black phosphorus nanosheets and immunoadjuvant for photoimmunotherapy of melanoma.

Photoimmunotherapy, which combines local photothermal therapy (PTT) with immunological stimulation, is a promising modality for cancer treatment. Herein, we have reported a photothermal-immunotherapy of melanoma using pegylated black phosphorus nanosheets (BP-PEG NSs) and imiquimod (R837) as the photothermal conversion agent and the immunoadjuvant, respectively. The photothermal stability of BP NSs was remarkably enhanced after the modification of poly(ethylene glycol) (PEG) by electrostatic interactions. The in situ generation of tumor-associated antigens by PTT elicited a strong immune response in the presence of R837, achieving a photoimmunotherapy of B16 melanoma. This photoimmunotherapy stimulated a stronger immune response both in vitro and in vivo than monotherapy, inducing a much greater release of cytokines such as IL-6, IL-12, and TNF-α. In vivo antitumor studies in B16 tumor-bearing mice demonstrated that photoimmunotherapy showed the best tumor inhibition effects. Our study suggested that BP-PEG NS-based PTT primed with an immunoadjuvant can be used for synergistic photoimmunotherapy of melanomas.

Functional profiles of phycospheric microorganisms during a marine dinoflagellate bloom.

Harmful algal blooms (HABs) are an ecological concern but relatively few studies have investigated the functional potential of bacterioplankton over a complete algal bloom cycle, which is critical for determining their contribution to the fate of algal blooms. To address this point, we carried out a time-series metagenomic analysis of the functional features of microbial communities at three different Gymnodinium catenatum bloom stages (pre-, peak-, and post-bloom). Different microbial composition were observed during the blooming stages. The environmental parameters and correlation networks co-contribute to microbial variability, and the former explained 38.4% of total variations of the bacterioplankton community composition. Functionally, a range of pathways involved in carbon, nitrogen, phosphorus and sulfur cycling were significantly different during the various HAB stages. Genes associated with carbohydrate-active enzymes, denitrification, and iron oxidation were enriched at the pre-bloom stage; genes involved in reductive citrate cycle for carbon fixation, carbon degradation, nitrification and phosphate transport were enhanced at the peak stage; and relative gene abundance related to sulfur oxidation, vitamin synthesis, and iron transport and storage was increased at the post-bloom stage. The ecological linkage analysis has shown that microbial functional potential especially the C/P/Fe metabolism were significantly linked to the fate of the algal blooms. Taken together, our results demonstrated that microorganisms displayed successional patterns not only at the community level, but also in the metabolic potential on HAB's progression. This work contributes to a growing understanding of microbial structural elasticity and functional plasticity and shed light on the potential mechanisms of microbial-mediated HAB trajectory.