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Epidemiological studies have demonstrated the association between exposure to fine particulate matter (PM2.5) and the onset of Non-alcoholic fatty liver disease (NAFLD). However, the potential biological mechanism is largely unknown. Our study was aimed to explore the impact of PM2.5 on the transcriptome level in the liver of ob/ob mice by atmosphere PM2.5 whole-body dynamic exposure system, and meanwhile preliminarily investigated the effects of metformin intervention in this process. 3,574 differentially expressed genes (DEGs) was screened out by microarray analysis (p1.5). KEGG pathway enrichment analysis showed that these DEGs were mainly enriched in cancers, infectious diseases and signal transduction, and the most significant pathway were thyroid hormone signaling pathway, chronic myeloid leukemia and metabolic pathways. Then, 12 hub genes were gained through weighted gene correlation network analysis (WGCNA) and verified by qRT-PCR. The expression of 5 genes in darkslateblue module (cd53, fcer1g, cd68, ctss, laptm5) increased after PM2.5 exposure, and decreased after metformin intervention. They were related to insulin resistance, glucose and lipid metabolism and other liver metabolism, and also neurodegenerative diseases. This study provided valuable clues and possible protective measures to the liver damage in ob/ob mice caused by PM2.5 exposure, and further research is needed to explore the related mechanism in detail.

Air pollution is one of the biggest environmental health problems in the world; accumulative studies have shown that air pollution was closely related to metabolism disorders. HbA1c is a stable indicator for blood glucose level monitoring. However, studies on the impact of ambient air pollution on HbA1c have inconsistent conclusions. The objective of the study is to explore the influence of ambient air pollution on HbA1c. By searching keywords, a systematic literature retrieval was carried out on PubMed, Cochrane Library, Web of Science, and Embase databases up to April 2022. Pooled percentage change (%-change) and 95% confidence intervals (95% CI) were estimated using random effect models for particulate matter (PM) and nitrogen dioxide (NO

Autophagy is an important protective mechanism in maintaining or restoring cell homeostasis under physiological and pathological conditions. Nanoparticles (NPs) with certain components and morphologies can induce autophagic responses in cancer cells, providing a new perspective for establishing cancer therapy strategies. Herein, a novel nanodrug system, cell membranes-coated zeolitic imidazolate framework-8 (ZIF-8) NPs encapsulating chloroquine (CQ) and glucose oxidase (GOx) (defined as mCG@ZIF), is designed to achieve an enhanced anticancer effect with the combination of starvation therapy and an autophagy regulation strategy. It is found that ZIF-8 as a nanocarrier can induce autophagy to promote survival of cancer cells via the upstream Zn

Short-term SiNPs exposure activated ferritinophagy in hepatocytes, which was responsible for subsequent ferroptosis and ultimately liver injury.

Exposure to fine particulate matter (PM

Fine particulate matter (PM

Current chemodynamic therapy (CDT) primarily relies on the delivery of transition metal ions with Fenton activity to trigger hydroxyl radical production from hydrogen peroxide. However, administration of an excess amount of exogenous Fenton-type heavy metals may cause potential adverse effects to human health, including acute and chronic damages. Here, we present a new CDT strategy that uses intracellular labile iron pool (LIP) as the endogenous source of Fenton-reactive metals for eliciting free radical generation, and the discovery of hydroperoxides (R'OOH) as an optimal LIP-mediated chemodynamic agent against cancer. By simulating the metabolic fates of peroxo compounds within cells, R'OOH was found to have excellent free radical-producing ability in the presence of labile iron(II) and to suffer only moderate elimination by glutathione/glutathione peroxidase, which contributes to its superior chemodynamic efficacy. The LIP-initiated nontoxic-to-toxic transition of R'OOH, together with increased LIP levels in tumor cells, enabled efficient and specific CDT of cancer. Moreover, pH/labile iron(II) cascade-responsive nanomedicines comprising encapsulated methyl linoleate hydroperoxide and LIP-increasing agent in pH-sensitive polymer particles were fabricated to realize enhanced CDT. This work not only paves the way to using endogenous Fenton-type metals for cancer therapy but also offers a paradigm for the exploration of high-performance chemodynamic agents activated by intracellular LIP.

Multimodal imaging in the second near-infrared window (NIR-II) guided cancer therapy is a highly precise and efficient cancer theranostic strategy. However, it is still a challenge to develop activated NIR-II optical imaging and therapy agents. In this study, we develop a pH-responsive hybrid plasmonic-fluorescent vesicle by self-assembly of amphiphilic plasmonic nanogapped gold nanorod (AuNNR) and fluorescent down-conversion nanoparticles (DCNP) (AuNNR-DCNP Ve), showing remarkable and activated NIR-II fluorescence (FL)/NIR-II photoacoustic (PA) imaging performances. The hybrid vesicle also exhibited superior loading capacity of doxorubicin as a superior drug carrier and efficient radiosensitizer for X-ray-induced radiotherapy. Interestingly, the accumulated hybrid AuNNR-DCNP Ve in the tumor resulted in a recovery of NIR-II FL imaging signal and a variation in NIR-II PA imaging signal. Dual activated NIR-II PA and FL imaging of the hybrid vesicle could trace drug release and precisely guided cancer radiotherapy to ultimately reduce the side effects to healthy tissue.

Nanoscale metal-organic frameworks (nano MOFs) have emerged as a promising biomedical nanoplatform because of their unique properties. However, the exploration of nano MOFs in photoacoustic (PA) imaging is still limited. Here, a novel hydrogen sulfide (H2S)-activated nano copper-based MOF (Cu-MOF) was developed as a near-infrared (NIR) ratiometric PA probe for in vivo monitoring of endogenous H2S level and orthotopic colorectal cancer imaging via in situ reaction of nano Cu-MOFs with endogenous H2S that is closely associated with tumor growth and proliferation in colon cancer. The synthesized nano Cu-MOFs displayed excellent PA responsiveness towards tumor H2S level with high selectivity and rapid kinetics. The result suggests the developed probe may provide a unique opportunity to investigate the malignant behaviors of H2S-associated events in vivo.

Immunogenic cell death (ICD) elicited by photodynamic therapy (PDT) is mediated through generation of reactive oxygen species (ROS) that induce endoplasmic reticulum (ER) stress. However, the half-life of ROS is very short and the intracellular diffusion depth is limited, which impairs ER localization and thus limits ER stress induction. To solve the problem, we synthesized reduction-sensitive Ds-sP NPs (PEG-s-s-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] nanoparticles) loaded with an efficient ER-targeting photosensitizer TCPP-TER (4,4',4″,4'″-(porphyrin-5,10,15,20-tetrayl)tetrakis(N-(2-((4-methylphenyl)sulfonamido)ethyl)benzamide). The resulting Ds-sP/TCPP-TER NPs could selectively accumulate in the ER and locally generate ROS under near-infrared (NIR) laser irradiation, which induced ER stress, amplified ICD, and activated immune cells, leading to augmented immunotherapy effect. This study presents a novel ICD amplifying, ER-targeting PDT strategy that can effectively eradicate primary tumors under NIR exposure, as well as distant tumors through an abscopal effect.

A growing number of epidemiological evidence reveals that electronic cigarettes (E-cigs) were associated with pneumonia, hypertension and atherosclerosis, but the toxicological evaluation and mechanism of E-cigs were largely unknown.Our study was aimed to explore the adverse effects on organs and metabolomics changes in C57BL/6J mice after acute exposure to E-cigs.Hematoxylin and eosin (HE) staining found pathological changes in tissues after acute exposure to E-cigs, such as inflammatory cell infiltration, nuclear pyknosis, and intercellular interstitial enlargement. E-cigs could increase apoptosis-positive cells in a time-dependent way using Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Oxidative damage indicators of reactive oxygen species (ROS), malondialdehyde (MDA) and 4-hydroxynonena (4-HNE) were also elevated after E-cigs exposure. There was an increasing trend of total glycerol and cholesterol in serum, while the glucose and liver enzymes including alanine aminotransferase (ALT), aspartate transaminase (AST), gamma-glutamyltranspeptidase (γ-GT) had no significant change compared to that of control. Further, Q Exactive high field (HF) mass spectrometer was used to conduct metabolomics, which revealed that differential metabolites including l-carnitine, Capryloyl glycine, etc. Trend analysis showed the type of compounds that change over time. Pathway enrichment analysis indicated that E-cigs affected 24 metabolic pathways, which were mainly regulated amino acid metabolism, further affected the tricarboxylic acid (TCA) cycle. Additionally, metabolites-diseases network analysis found that the type 2 diabetes mellitus, propionic acidemia, defect in long-chain fatty acids transport and lung cancer may be related to E-cigs exposure.Our findings provided important clues for metabolites biomarkers of E-cigs acute exposure and are beneficial for disease prevention.

Multiple drug-resistance mechanisms originate from defensive pathways in cancer and are associated with the unsatisfied efficacy of chemotherapy. The combination of small interfering RNA (siRNA) and chemotherapeutics provides a strategy for reducing drug efflux but requires more delivery options for clinical translation. Herein, multidrug resistance protein 1 (MDR1) siRNA is used as the skeleton to assemble chemotherapeutic cisplatin (CDDP) and divalent copper ion (Cu

It is reported that oxidative stress homeostasis was involved in PM

Fine particulate matter (PM

Air pollution, especially PM

Short-term PM2.5 exposure is related to vascular remodeling and stiffness. Mitochondria-targeted antioxidant MitoQ is reported to improve the occurrence and development of mitochondrial redox-related diseases. At present, there is limited data on whether MitoQ can alleviate the vascular damage caused by PM2.5. Therefore, the current study was aimed to evaluate the protective role of MitoQ on aortic fibrosis induced by PM2.5 exposure. Vascular Doppler ultrasound manifested PM2.5 damaged both vascular function and structure in C57BL/6J mice. Histopathological analysis found that PM2.5 induced aortic fibrosis and disordered elastic fibers, accompanied by collagen I/III deposition and synthetic phenotype remodeling of vascular smooth muscle cells; while these alterations were partially alleviated following MitoQ treatment. We further demonstrated that mitochondrial dysfunction, including mitochondrial reactive oxygen species (ROS) overproduction and activated superoxide dismutase 2 (SOD2) expression, decreased mitochondrial membrane potential (MMP), oxygen consumption rate (OCR), ATP and increased intracellular Ca2+, as well as mitochondrial fragmentation caused by increased Drp1 expression and decreased Mfn2 expression, occurred in PM2.5-exposed aorta or human aortic vascular smooth muscle cells (HAVSMCs), which were reversed by MitoQ. Moreover, the enhanced expressions of LC3II/I, p62, PINK1 and Parkin regulated mitophagy in PM2.5-exposed aorta and HAVSMCs were weakened by MitoQ. Transfection with PINK1 siRNA in PM2.5-exposed HAVSMCs further improved the effects of MitoQ on HAVSMCs synthetic phenotype remodeling, mitochondrial fragmentation and mitophagy. In summary, our data demonstrated that MitoQ treatment had a protective role in aortic fibrosis after PM2.5 exposure through mitochondrial quality control, which regulated by mitochondrial ROS/PINK1/Parkin-mediated mitophagy. Our study provides a possible targeted therapy for PM2.5-induced arterial stiffness., Graphical abstract Image 1

Combination therapy that could better balance immune activation and suppressive signals holds great potential in cancer immunotherapy. Herein, we serendipitously found that the pH-responsive nanovesicles (pRNVs) self-assembled from block copolymer polyethylene glycol-b-cationic polypeptide can not only serve as a nanocarrier but also cause immunogenic cell death (ICD) through preapoptotic exposure of calreticulin. After coencapsulation of a photosensitizer, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) and an indoleamine 2,3-dioxygenase inhibitor, indoximod (IND), pRNVs/HPPH/IND at a single low dose elicited significant antitumor efficacy and abscopal effect following laser irradiation in a B16F10 melanoma tumor model. Treatment efficacy attributes to three key factors: (i) singlet oxygen generation by HPPH-mediated photodynamic therapy (PDT); (ii) increased dendritic cell (DC) recruitment and immune response provocation after ICD induced by pRNVs and PDT; and (iii) tumor microenvironment modulation by IND via enhancing P-S6K phosphorylation for CD8+ T cell development. This study exploited the nanocarrier to induce ICD for the host's immunity activation. The "all-in-one" smart nanovesicles allow the design of multifunctional materials to strengthen cancer immunotherapy efficacy.

Reactive oxygen species (ROS) can be used not only as a therapeutic agent for chemodynamic therapy (CDT), but also as a stimulus to activate release of antitumor drugs, achieving enhanced efficacy through the combination of CDT and chemotherapy. Here we report a pH/ROS dual-responsive nanomedicine consisting of β-lapachone (Lap), a pH-responsive polymer, and a ROS-responsive polyprodrug. In the intracellular acidic environment, the nanomedicine can realize pH-triggered disassembly. The released Lap can efficiently generate hydrogen peroxide, which will be further converted into highly toxic hydroxyl radicals via the Fenton reaction. Subsequently, through ROS-induced cleavage of thioketal linker, doxorubicin is released from the polyprodrug. In vivo results indicate that the cascade of ROS generation and antitumor-drug release can effectively inhibit tumor growth. This design of nanomedicine with cascade reactions offers a promising strategy to enhance antitumor efficacy.

Chemodynamic therapy (CDT) employs Fenton catalysts to kill cancer cells by converting intracellular H2O2 into hydroxyl radical (•OH), but endogenous H2O2 is insufficient to achieve satisfactory anticancer efficacy. Despite tremendous efforts, engineering CDT agents with specific and efficient H2O2 self-supplying ability remains a great challenge. Here, we report the fabrication of copper peroxide (CP) nanodot, which is the first example of a Fenton-type metal peroxide nanomaterial, and its use as an activatable agent for enhanced CDT by self-supplying H2O2. The CP nanodots were prepared through coordination of H2O2 to Cu2+ with the aid of hydroxide ion, which could be reversed by acid treatment. After endocytosis into tumor cells, acidic environment of endo/lysosomes accelerated the dissociation of CP nanodots, allowing simultaneous release of Fenton catalytic Cu2+ and H2O2 accompanied by a Fenton-type reaction between them. The resulting •OH induced lysosomal membrane permeabilization through lipid peroxidation and thus caused cell death via a lysosome-associated pathway. In addition to pH-dependent •OH generation property, CP nanodots with small particle size showed high tumor accumulation after intravenous administration, which enabled effective tumor growth inhibition with minimal side effects in vivo. Our work not only provides the first paradigm for fabricating Fenton-type metal peroxide nanomaterials, but also presents a new strategy to improve CDT efficacy.

Nanomedicines with photodynamic therapy and reactive oxygen species (ROS)‐triggered drug release capabilities are promising for cancer therapy. However, most of the nanomedicines based on ROS‐responsive nanocarriers still suffer from serious ROS consumption during the triggered drug release process. Herein, a photodynamic‐chemodynamic cascade strategy for the design of drug delivery nanosystem is proposed. A doxorubicin hydrochloride‐loaded ROS‐responsive polymersome (DOX‐RPS) is prepared via the self‐assembly of amphiphilic poly(ethylene glycol)‐poly(linoleic acid) and poly(ethylene glycol)‐(2‐(1‐hexyloxyethyl)‐2‐devinyl pyropheophorbide‐α)‐iron chelate (PEG‐HPPH‐Fe). The RPS can effectively deliver a drug to tumor site through passive targeting effect. Upon laser irradiation, the photosensitizer HPPH can efficiently generate ROS, which further causes in situ oxidation of linoleic acid chain and subsequent RPS structural destruction, permitting triggered drug release. Intriguingly, catalyzed by HPPH‐Fe, ROS will be regenerated from linoleic acid peroxide through a chemodynamic process. Therefore, ROS‐triggered drug release can be achieved without ROS over‐consumption. The in vitro and in vivo results confirmed ROS generation, triggered drug release behavior, and potent antitumor effect of the DOX‐RPS. This photodynamic‐chemodynamic cascade strategy provides a promising approach for enhanced combination therapy., Photodynamic‐chemodynamic cascade strategy: A reactive oxygen species (ROS)‐responsive polymersome is developed for chemo‐photodynamic combination cancer therapy. The ROS generated by photodynamic effect will cause ROS‐triggered drug release. Furthermore, ROS could be regenerated through a Fenton‐like reaction. Therefore, excessive ROS consumption in the drug release process can be avoided.

Fine particle matter (PM

Among various air pollutants, particulate matter (PM) is the most harmful and representative pollutant. Although several studies have shown a link between particulate pollution and obesity, the conclusions are still inconsistent.We conducted a systematic review and meta-analysis to pool the effect of PM exposure on obesity. Five databases (including PubMed, Web of Science, Scopus, Embase, and Cochrane) were searched for relevant studies up to Jan 2022. Adjusted risk ratio (RR) with corresponding 95% confidence interval (CI) were retrieved from individual studies and pooled with random effect models by STATA software. Besides, we tested the stability of results by Egger's test, Begg's test, funnel plot, and using the trim-and-fill method to modify the possible asymmetric funnel graph. The NTP-OHAT guidelines were followed to assess the risk of bias. Then the GRADE was used to evaluate the certainty of evidence.26 studies were included in this meta-analysis. 19 studies have shown that PMExposure to PM

Immunomodulation of macrophages against cancer has emerged as an encouraging therapeutic strategy. However, there exist two major challenges in effectively activating macrophages for antitumor immunotherapy. First, ligation of signal regulatory protein alpha (SIRPα) on macrophages to CD47, a "don't eat me" signal on cancer cells, prevents macrophage phagocytosis of cancer cells. Second, colony stimulating factors, secreted by cancer cells, polarize tumor-associated macrophages (TAMs) to a tumorigenic M2 phenotype. Here, it is reported that genetically engineered cell-membrane-coated magnetic nanoparticles (gCM-MNs) can disable both mechanisms. The gCM shell genetically overexpressing SIRPα variants with remarkable affinity efficiently blocks the CD47-SIRPα pathway while the MN core promotes M2 TAM repolarization, synergistically triggering potent macrophage immune responses. Moreover, the gCM shell protects the MNs from immune clearance; and in turn, the MN core delivers the gCMs into tumor tissues under magnetic navigation, effectively promoting their systemic circulation and tumor accumulation. In melanoma and breast cancer models, it is shown that gCM-MNs significantly prolong overall mouse survival by controlling both local tumor growth and distant tumor metastasis. The combination of cell-membrane-coating nanotechnology and genetic editing technique offers a safe and robust strategy in activating the body's immune responses for cancer immunotherapy.

Among various air pollutants, particulate matter (PM) is the most harmful and representative pollutant. At the same time, allergic rhinitis (AR) is getting more and more attention, so we explore the relationship between PM and the prevalence of AR among children. Then, PubMed, Web of Science, Google Scholar was used to search for relevant studies up to January 2020. Literature quality assessment was processed using the Newcastle-Ottawa Scale (NOS) evaluation scale. Adjusted odds ratio (OR) with corresponding 95% confidence interval (CI) was retrieved from individual studies and pooled to generate a summary effect via STATA software. Besides, we test the result stability by Egger’s test and funnel plot, and using the trim-and-fill method to modify the possible asymmetric funnel graph. 21 studies were included in the meta-analysis. 9 articles reported about PM2.5 on childhood AR (1.09, 95%CI: 1.01, 1.17, per 10 μg/m3 increase). 15 articles reported about PM10 on childhood AR (1.06, 95%CI: 1.02,1.11, per 10 μg/m3 increase), PM2.5 exposure has a bigger effect on children AR than PM10. In addition, a series of subgroup analysis was performed, and we found that PM2.5 and PM10 have different performances in different subgroups. In addition to this, we analyzed the sources of heterogeneity of the study. Apart from the results we got all have good stability without publication bias. Therefore, it can be concluded that exposure to PM may increase the prevalence of AR among children.

Organic prodrugs have been widely reported to avoid side effects and have been applied for precise tumor therapy in recent years. However, inorganic nano-prodrugs with localized generation of toxic products in the tumor have not been reported. Herein, we report an inorganic nano-prodrug, tellurium nanowires (TeNWs), that generate toxic TeO66− triggered by hydrogen peroxide (H2O2) for highly selective cancer chemotherapy. Bovine serum albumin and dextran conjugate coated TeNWs, with a length of ∼82 nm and a width of ∼7 nm, showed high stability in physiological medium. The interaction between TeNWs and intracellular H2O2 produces toxic TeO66− molecules greatly enhanced ROS generation, and the reaction product, verified as TeO66−, would react with glutathione (GSH) and thus decrease intracellular GSH levels, which greatly increases ROS levels in the tumor. Importantly, TeNWs selectively kill cancer cells by caspase-independent autophagic death and apoptosis, as well as exerting an immune response, while not affecting normal cells due to the high H2O2 levels in cancer cells. Moreover, after the sequential reaction with H2O2 and GSH, TeNWs were dissociated into small molecules and could be rapidly and completely removed from the body. Both in vitro and in vivo experiments indicate that TeNWs are a promising inorganic nano-prodrug that exerts good selective therapeutic effects on tumors.

The design of hybrid metal-organic framework (MOF) nanomaterials by integrating inorganic nanoparticle into MOF (NP@MOF) has demonstrated outstanding potential for obtaining enhanced, collective, and extended novel physiochemical properties. However, the reverse structure of MOF-integrated inorganic nanoparticle (MOF@NP) with multifunction has rarely been reported. Methods: We developed a facile in-situ growth method to integrate MOF nanoparticle into inorganic nanomaterial and designed a fluorescence switch to trigger enhanced photodynamic therapy. The influence of “switch” on the photodynamic activity was studied in vitro. The in vivo mice with tumor model was applied to evaluate the “switch”-triggered enhanced photodynamic therapy efficacy. Results: A core-satellites structure with fluorescence off and on function was obtained when growing MnO2 on the surface of fluorescent zeolitic imidazolate framework (ZIF-8) nanoparticles. Furthermore, A core-shell structure with photodynamic activity off and on function was achieved by growing MnO2 on the surface of porphyrinic ZrMOF nanoparticles (ZrMOF@MnO2). Both the fluorescence and photodynamic activities can be turned off by MnO2 and turned on by GSH. The GSH-responsive activation of photodynamic activity of ZrMOF@MnO2 significantly depleted the intracellular GSH via a MnO2 reduction reaction, thus triggering an enhanced photodynamic therapy efficacy. Finally, the GSH-reduced Mn2+ provided a platform for magnetic resonance imaging-guided tumor therapy. Conclusion: This work highlights the impact of inorganic nanomaterial on the MOF properties and provides insight to the rational design of multifunctional MOF-inorganic nanomaterial complexes.

A Pt prodrug polyphenol and gadolinium ion loaded cancer theranostics nanoplatform based on mild acidic pH and thermal sensitive polymer was designed for photoacoustic (PA)/ magnetic resonance(MR)/ positron emission tomography (PET) multimodal imaging-guided chemo-photothermal combination therapy. The Pt drug release can be controlled by tumour-specific acidic pH and heat generated by external NIR irradiation. The nanoparticles were stable under normal physiological environment and released the drug under tumour acidic pH and NIR laser irradiation, which can reduce the side effect of drug to normal organs. Moreover, the MR signal can be significantly enhanced (~3-fold increase in T1 relaxivity) under the acidic tumour microenvironment, which is favorable for cancer diagnosis. The nanoparticles exhibited excellent tumour accumulation and led to complete tumour eradication with low power NIR laser irradiation. This promising approach provides a new avenue for imaging-guided combination therapy.

Ambient air pollution is recognized as a major threat to those with cardiovascular disease (CVD), especially among old adults within this high risk group. Heart rate variability (HRV) is a marker of cardiac autonomic system, which links air pollution and CVD. However, the relationship between PM and HRV has been inconsistently reported. To investigate the associations of PM

Ambient fine particulate matter (PMTo explore the influence of short-term PMBy using a combination of computer and manual retrieval, a systematic literature retrieval was conducted on PubMed, Cochrane Library, Web of Science, Embase and Scopus databases up to October 2019. The heterogeneity among studies was tested by Stata 12.0, and the pooled %-change (percentage change per 10 μg/m12 articles were included in this meta-analysis. Short-term PMShort-term PM

Lung adenocarcinoma (LUAD) is a frequently diagnosed histologic subtype with increasing morbidity and mortality. RalGDS-Like 4 (RGL4) has not been reported to be associated with cancer risk, prognosis, immunotherapy or any other treatments. We perform a bioinformatics analysis on data downloaded from the Cancer Genome Atlas (TCGA)-LUAD, and we find that low expression of RGL4 is accompanied by worse outcomes and prognosis in LUAD patients. As a promising predictor, the potential influence and mechanisms of RGL4 on overall survival are worth exploring. Moreover, RGL4 expression is significantly associated with a variety of tumor-infiltrating immune cells (TIICs), particularly memory B cells, CD8+T cells and neutrophils. Subsequently, we evaluated the most notable KEGG pathways, including glycolysis gluconeogenesis, the P53 signaling pathway, RNA degradation, and the B cell receptor signaling pathway, among others. Our findings provide evidence that the decreased expression of RGL4 is significantly associated with poor prognosis and immune cell infiltration in patients with LUAD and highlight the use of RGL4 as a novel predictive biomarker for the prognosis of LUAD and other cancers. RGL4 may also be used in combination with immune checkpoints to identify the benefits of immunotherapy. Subjects: Bioinformatics, Genomics, Oncology, Thoracic surgery.

Tumor-specific phototheranostics is conducive to realizing precise cancer therapy. Herein, we rationally designed a novel tumor microenvironment (TME)-responsive phototheranostic paradigm based on an excellent match-up of semiconducting polymer brush and polyoxometalate cluster (SPB@POM). On the one hand, the acidic TME could drive the self-assembly of SPB@POM into bigger aggregates for enhanced tumor retention and accumulation. On the other hand, the reductive TME could significantly enhance the NIR absorption of SPB@POM for significant improvement of photoacoustic imaging contrast and photothermal therapy efficacy. Therefore, the intelligent acidity/reducibility dual-responsive SPB@POM allows for remarkable phototheranostic enhancement under the unique TME, which serves as a representative paradigm of nanotechnology in the judicious design of organic/inorganic hybrid nanomaterials for precise tumor-specific phototheranostics with minimal side effects.

Chemodynamic therapy (CDT) utilizes iron-initiated Fenton chemistry to destroy tumor cells by converting endogenous H2 O2 into the highly toxic hydroxyl radical (. OH). There is a paucity of Fenton-like metal-based CDT agents. Intracellular glutathione (GSH) with . OH scavenging ability greatly reduces CDT efficacy. A self-reinforcing CDT nanoagent based on MnO2 is reported that has both Fenton-like Mn2+ delivery and GSH depletion properties. In the presence of HCO3- , which is abundant in the physiological medium, Mn2+ exerts Fenton-like activity to generate . OH from H2 O2 . Upon uptake of MnO2 -coated mesoporous silica nanoparticles (MS@MnO2 NPs) by cancer cells, the MnO2 shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn2+ , resulting in GSH depletion-enhanced CDT. This, together with the GSH-activated MRI contrast effect and dissociation of MnO2 , allows MS@MnO2 NPs to achieve MRI-monitored chemo-chemodynamic combination therapy.

The recently emerged exceedingly small magnetic iron oxide nanoparticles (ES-MIONs) (