Enhancement of wastewater treatment by underwater superelastic fiber-penetrated lamellar monolith.

During the removal of pollutants from wastewater, the underwater compressibility of three-dimensional biomass materials is the main factor determining their properties and service life. To construct a chitosan (CS)-based material with underwater superelasticity, a bidirectional freezing technique was used to introduce bamboo fibers (BFs) as bridges between CS lamellae to form a biomimetic CS/BFs monolith with an architecture similar to Thalia dealbata stems. BFs completely penetrated CS lamellae from the top down, which served as springs to dampen the elastic deformation during compressive cycles. After 10,000 underwater compressive cycles at 60% strain, the plastic deformation was negligible, and after 100 cycles at 90% strain, the monolith retained 93.8% of the maximum stress. Moreover, the CS/BFs monolith was loaded with CaCO3 nanoparticles via compression-release-compression to obtain a CS/BFs/CaCO3 monolith that exhibited excellent water purification capabilities. The CS/BFs/CaCO3 monolith removed water-soluble dyes, heavy-metal ions, and emulsified oils from water with a high separation efficiency by simple squeezing and pumping methods. The novel pumping technology using the CS/BFs/CaCO3 monolith provides a facile and rapid method to separate oil-in-water emulsions (maximum water flux of 11,776.9 L m-2 h-1). Therefore, the CS/BFs/CaCO3 monolith with underwater superelasticity has great potential applications for wastewater treatment.

Crocin-I alleviates the depression-like behaviors probably via modulating "microbiota-gut-brain" axis in mice exposed to chronic restraint stress.

BACKGROUND: Depressive disorder is rapidly advancing in the worldwide, and therapeutic strategy through "gut-brain" axis has been proved to be effective. Crocin, has been found to have antidepressant activity. However, there is no thorough research for the effects of crocin-I (a major active component of crocin) on depression and its underlying mechanism. METHODS: We investigated the antidepressant effect of six-week oral administration of crocin-I in a mice model of depression induced by four-week CRS. Based on the "microbiota-gut-brain" axis, we determined the effects of crocin-I administration on gut microbiota, intestinal barrier function, short chain fatty acids and neurochemical indicators. RESULTS: Administration of crocin-I at a dose of 40 mg/kg for six weeks mitigated depression-like behaviors of depressed mice as evidenced by behaviors tests. In addition, crocin-I reduced the levels of lipopolysaccharide (LPS), Interleukin-6and tumor necrosis factor-α (TNF-α) in serum and TNF-α expression in the hippocampus, and increased the hippocampal brain-derived neurotrophic factor. Besides, 16 s rRNA sequencing revealed that crocin-I mitigated the gut microbiota dysbiosis in depressed mice as represented by the decreased abundance of Proteobacteria and Bacteroidetes, Sutterella spp. and Ruminococcus spp. and increased abundances of Firmicutes, Lactobacillus spp. and Bacteroides spp. Moreover, gas chromatography-mass spectrometry revealed that crocin-I reversed the decreased levels of short-chain fatty acids (SCFAs) in feces of depressed mice. Furthermore, crocin-I improved the impaired intestinal barrier by increasing expression of Occludin and Claudin-1, which contributed to the decreased LPS leakage. LIMITATIONS: Only the male mice were used; the dose-effect relationship should be observed. CONCLUSION: These results suggested that crocin-I effectively alleviated depression-like behavior, likely depended on the gut microbiota and its modulation of intestinal barrier and SCFAs.

Exposure to low concentration of trifluoromethanesulfonic acid induces the disorders of liver lipid metabolism and gut microbiota in mice.

Trifluoromethanesulfonic acid (TFMS) is the shortest chain perfluorinated compound. Recently, it has been identified as a persistent and mobile organic chemical with a maximum concentration of 1 µg/L in the environment. However, its toxicological mechanism remains unclear. In this study, to evaluate the liver and intestinal toxicity of TFMS in mammals, male mice were orally exposed to 0, 1, 10 and 100 µg/kg for 12 weeks. Our results showed that TFMS exposure reduced the epididymal fat weight in mice, caused the decrease of serum and liver triglyceride (TG) level and the increase of serum low density lipoprotein (LDL) level. Also, we observed the inflammatory cell infiltration in the liver of mice exposed to 10 µg/kg and 100 µg/kg TFMS, which was coupled with the increased mRNA expression levels of inflammatory factors such as COX2, TNF-α, IL-1ß in the liver. In addition, the mRNA expression levels of lipid metabolism-related genes (PPAR-α, ACOX, SCD1, PPAR-γ, etc.) were significantly decreased in the liver of mice after exposure to both doses of TFMS. We also found TFMS exposure caused the imbalance of cecal gut microbiota and change of cecal microbiota diversity. KEGG pathway predictions showed that the exposure of 100 µg/kg TFMS changed the synthesis and degradation of ketone bodies, benzoate degradation and several other metabolic pathways. Our findings indicated that TFMS exposure disturbed the liver lipid metabolism possibly via altering the gut microbiota.

Inhibition of carrageenan-induced dental inflammatory responses owing to decreased TRPV1 activity by Dexmedetomidine.

BACKGROUND: Dexmedetomidine (Dex) is a highly selective agonist of the α2 adrenergic receptor and a common sedative; however, its anti-inflammatory effect has been studied. In this study, the inhibitory effect of Dex on inflammation in dental pulp cells was assessed. For this, the effect of Dex on inflammation induced by carrageenan (Car) in human dental pulp cells (hDPCs) was evaluated. Car incubation induced a robust inflammatory response in hDPCs as well as activation of PKA-STAT3 and PKC-nuclear factor kappa B (NF-κB) signaling pathways. RESULTS: Dex reduced the expression of inflammatory cytokines in a dose-dependent manner. Meanwhile, the phosphorylation of PKA, PKC, STAT3, and NF-κB as well as the nuclear accumulation of STAT3 and NF-κB were significantly increased in Dex-treated Car-induced hDPCs. Western blotting results also showed that the phosphorylation level of transient receptor potential cation channel subfamily V member 1 (TRPV1) was downregulated as a result of Dex treatment. Furthermore, we found that administration of the TRPV1 agonist capsaicin (Cap) reversed the effects of Dex on proinflammatory cytokines; however, the expression and activation of PKA-STAT3 and PKC-NF-κB signals were not altered owing to Cap administration. CONCLUSIONS: These results indicate that Dex plays a defensive role in dental pulp inflammation by regulating the TRPV1 channel and can be used as a potential target for human dental pulp inflammation intervention.

Depression-like behaviors are accompanied by disrupted mitochondrial energy metabolism in chronic corticosterone-induced mice.

Stress exerts its negative effects by interference with mitochondrial energy production in rodents, and is able to impair mitochondrial bioenergetics. However, the underlying mechanism that stress hormone impacts depression-like behaviors and mitochondrial energy metabolism is still not well understood. Here, we investigated the changes of depression-like behaviors and mitochondrial energy metabolism induced by chronic corticosterone (CORT). The results showed that after treatment with CORT for 6 weeks, mice displayed depression-like behaviors, which were identified by tail suspension test, forced swimming test and open field test. Then, the livers were isolated and tested by RNA sequencing and metabolome analysis. RNA sequencing showed 354 up-regulated genes and 284 down-regulated genes, and metabolome analysis revealed 280 metabolites with increased abundances and 193 metabolites with reduced abundances in the liver of mice after CORT, which were closely associated with lipid metabolism and oxidative phosphorylation in mitochondria. Based on these findings, the changes of mitochondrial energy metabolism were investigated, and we revealed that CORT condition inhibited glycolysis and fatty acid degradation pathway, and activated synthesis of triacylglycerol, leading to the reduced levels of acetyl-CoA and attenuated TCA cycle. Also, the pathways of NAD+ synthesis were inhibited, resulting in the reduced activity of sirtuin 3 (SIRT3). Thus, all of these observations disrupted the function of mitochondria, and led to the decrease of ATP production. Our findings uncover a novel mechanism of stress on depression-like behaviors and mitochondrial energy metabolism in rodents.

Artesunate targets oral tongue squamous cell carcinoma via mitochondrial dysfunction-dependent oxidative damage and Akt/AMPK/mTOR inhibition.

Although mitochondrial metabolism has recently gained attention as a promising therapeutic strategy in cancer, little is known on the impact of mitochondrial respiration inhibition on oral tongue squamous cell carcinoma (OTSCC). Using in vitro and in vivo OTSCC models, our work demonstrates that inducing mitochondrial dysfunction by anti-malarial drug artesunate is effective in targeting OTSCC stem-cell like and bulk cells. Artesunate inhibits anchorage-independent colony formation, proliferation and survival in all tested OTSCC cell lines although with varying efficacy. Artesunate displays preferential anti-OTSCC activity by sparing normal cells. Mechanism analysis indicates that artesunate inhibits mitochondrial respiration via suppressing mitochondrial complex I and II but not IV or V, resulting in oxidative stress and damage. Interestingly, OTSCC cells that are more sensitive to artesunate have higher level of basal mitochondrial respiration and reversed respiratory capacity compared to those with less sensitivity to artesunate, suggesting the varying dependence on mitochondrial respiration among OTSCC cell lines. In addition, artesunate induces oxidative stress and damage in cells with low sensitivity to a less extent than in those with high sensitivity. We confirm that mitochondrial respiration inhibition is required for the action of artesunate in OTSCC. Mitochondrial dysfunction by artesunate further activates AMPK and suppresses Akt/mTOR. Importantly, the in vitro observations are reproducible in vivo OTSCC xenograft mouse model. Our findings provide pre-clinical evidence on the efficacy of artesunate and emphasize the therapeutic value of targeting mitochondrial respiration in OTSCC.

Nicotinamide mononucleotide ameliorates the depression-like behaviors and is associated with attenuating the disruption of mitochondrial bioenergetics in depressed mice.

BACKGROUND: Nicotinamide mononucleotide (NMN) has been shown to stimulate oxidative phosphorylation in mitochondria and to improve various pathologies in patients and mouse disease models. However, whether NMN mediates mitochondrial energy production and its mechanism of action in depressed animals remain unclear. METHODS: Mice were subcutaneously injected with corticosterone (CORT; 20 mg/kg) each day for 6 weeks, while another group was given an additional dose of NMN (300 mg/kg) by oral gavage in the last 2 weeks. Then, transcriptome analyses, metabolome analyses and transient gene knockdown in primary mouse cells were performed. RESULTS: NMN administration alleviated depression-like behavior and the liver weight to body weight ratio in a mouse model of CORT-induced depression. Transcriptome and metabolome analyses revealed that in depressed mice, NMN reduced the mRNA expression of genes involved in fatty acid synthesis, stimulation of ß-oxidation and glycolysis, and increased production of acetyl-coenzyme A for the tricarboxylic acid cycle. Importantly, NMN supplementation increased NAD+ levels to enhance sirtuin (SIRT)3 activity, thereby improving mitochondrial energy metabolism in the hippocampus and liver of CORT-treated mice. Sirt3knockdown in primary mouse astrocytes reversed the effect of NMN by inhibiting energy production, although it did not affect NAD+ synthesis LIMITATIONS: Group sample sizes were small, and only one type of primary mouse cell was used CONCLUSION: These results provide evidence for the beneficial role of NMN in energy production and suggest that therapeutic strategies that increase the level of NMN can be an effective treatment for depression.

Antidepressant activity of crocin-I is associated with amelioration of neuroinflammation and attenuates oxidative damage induced by corticosterone in mice.

Depression is the leading cause of mental health-related disease globally, and it affects an estimated 300 million people worldwide. However, its physiological causes are not fully understood. Since available antidepressants fail to achieve complete disease remission, treating diversification of depression may be a useful contribution. Crocin, one of the main glycosylated carotenoids of saffron, has been found to have numerous pharmacological activities and has been reported to be associated with neuroprotective effects. However, the biological action of crocin-I, a major member of the crocin family, on depression-like behavior, neuroinflammation and oxidative damage in depressed animals remains unclear. The present study showed that crocin-I exerts significant antidepressant effects in a model of chronic corticosterone (CORT)-induced depression, as evidenced by the attenuation of depression-like behaviors in the open field test, forced swimming test and tail suspension test. The antidepressant activity of crocin-I was probably achieved through the suppression of neuroinflammation (IL-1ß) and oxidative stress in the mouse hippocampus. Additionally, the oral administration of crocin-I at a dose of 40 mg/kg reduced the CORT-induced accumulation of nicotinamide in the liver of the mice to improve the synthesis of NAD+, thereby stimulating the activity of SIRT3 deacetylase to elevate the activity of antioxidants such as superoxide dismutase 2 and glutathione reductase. Moreover, crocin-I reduced the levels of oxidative damage markers (reactive oxygen species and malonaldehyde) to rescue impaired mitochondrial function caused by CORT treatment, which was represented by electron transport chain and oxidative phosphorylation normality, and thus rescue ATP production to the level of that in wild-type mice. Our findings shed new light on the mechanism of action of crocin-I on depression-like behavior and oxidative stress in individuals stressed by perceived conditions.

Crocin-I ameliorates the disruption of lipid metabolism and dysbiosis of the gut microbiota induced by chronic corticosterone in mice.

Glucocorticoids (GCs) are widely used as anti-inflammatory and immunosuppressive drugs. However, chronic treatment with GCs in clinical settings has a series of side effects, such as metabolic disorders, gut microbiota dysbiosis and neurological impairment. Therefore, searching for a functional substance that can alleviate these side effects is greatly meaningful to clinical patients. Crocin is the main active ingredient of saffron, which has been reported to have numerous pharmacological activities. However, the action of crocin-I, one major member of the crocin family, on the physiological mediation in the individuals receiving GC treatment remains unclear. In this study, we aimed to evaluate the efficacy of crocin-I on lipid metabolism and the gut microbiota in a mouse model of chronic corticosterone (CORT) treatment. Our findings showed that crocin-I reduced the levels of triglycerides and total cholesterol and the ratio of low density lipoprotein to high density lipoprotein in the serum of CORT-treated mice. In addition, transcriptome analysis revealed that crocin-I was effective in mediating the amelioration of lipid metabolism, mainly in fatty acid metabolism and steroid biosynthesis in CORT-treated mice. Moreover, metabolome analysis demonstrated that crocin-I could restore the disturbed metabolites in the liver of CORT-treated mice, most of which are long-chain fatty acids. Furthermore, high-throughput sequencing of 16s rRNA revealed that crocin-I could mitigate the dysbiosis of the gut microbiota caused by CORT at a dose of 40 mg kg-1, by resulting in a significant increase in the alpha diversity of the microbes in the cecal contents and a significant reduction in the abundance of Firmicutes, whereas by increasing the abundance of Bacteroidetes. These results indicated that oral administration of crocin-I could modify the composition of the gut microbiota and alleviate hepatic lipid disorder in mice treated with a high dose of GCs.

Exposure to jet lag aggravates depression-like behaviors and age-related phenotypes in rats subject to chronic corticosterone.

Our previous finding demonstrated that chronic corticosterone (CORT) may be involved in mediating the pathophysiology of premature aging in rats. Frequent jet lag increases the risk for many diseases, including obesity and type 2 diabetes, and is associated with the aging processes. However, the effect of jet lag on CORT-induced depression and its association with aging phenotypes remain unclear. In this study, the rats were exposed to both CORT and jet lag treatment, and the differences were analyzed and compared to rats with single CORT treatment. Our results showed that jet lag treatment aggravated CORT-induced depression-like behavior evidenced by sucrose intake test, forced swimming test, and open field test. Additionally, this treatment aggravated the shortening of telomeres, which possibly resulted in decreased telomerase activity, and downregulated the expression of telomere-binding factor 2 (TRF2) and telomerase reverse transcriptase compared to that in CORT rats, as revealed by quantitative real-time-polymerase chain reaction and western blot analysis, respectively. The shortening of telomeres may have been caused by increased oxidative stress, which was associated with the inhibition of sirtuin 3. Exposure to jet lag also aggravated the degeneration of mitochondrial functions, as shown by the decreases in the mRNA expression of COX1, ND1, and Tfam. Our findings provide physiological evidence that jet lag exposure may worsen stress-induced depression and age-related abnormalities.

Depression caused by long-term stress regulates premature aging and is possibly associated with disruption of circadian rhythms in mice.

Depression has been associated with circadian disruption and premature aging. Nevertheless, mechanisms underlying the link between long-term stress with premature aging and possible associations with circadian rhythms remain elusive. Here, mice were exposed to chronic mild stress for 16 weeks to induce depression-like symptoms, which were confirmed with the open field test, tail suspension test, and sucrose preference test. Then, the circadian rhythms of age-related indexes were compared between control and stressed mice. Long-term stress resulted in decreased body weight gain and locomotor activities, accompanied by losses of subcutaneous backside fat, decreased amounts of thigh muscle fibers, and shortened telomere length in hepatocytes. Stressed mice showed increased oxidative damage, causing impaired mitochondrial function and inflammatory responses, which may be mediated by the sirtuin 3 (SIRT3)-superoxide dismutase 2 (SOD2) signaling pathway. These changes may be associated with partial disruption of circadian rhythms or shifting phase values of some age-related indicators induced by long-term stress. These findings suggest that long-term exposure to stress may increase the risk of depression and regulate age-related phenotypes through associations with circadian rhythms.

Effect of chronic corticosterone-induced depression on circadian rhythms and age-related phenotypes in mice.

Disrupted circadian rhythms are a recognized effect of depression, and our previous article demonstrated an association between depression and premature aging, but the underlying mechanisms are not well understood. In the present study, we used a mouse model of chronic corticosterone (CORT)-treated depression to elucidate a mechanism by which depression may be associated with the circadian clock and mediate age-related phenotypes. Mice received a daily injection of 20 mg/kg CORT for 21 consecutive days, and the depression-like behaviors of mice were identified by the sucrose intake test, tail suspension test and open field test. Our findings indicated that CORT injection may be correlated with the circadian clock by impairing circadian rhythms or shifting the phase values of clock genes. We also showed that CORT-treated mice exhibited a significant gradual reduction in body weight gain with increased oxidative stress, including reduced activity of antioxidant-related enzymes, reduced glutathione:glutathione disulfide ratio and cytochrome (Cyt)-C level, and elevated reactive oxygen species content. Moreover, chronic CORT injection affected inflammatory responses, the production of mitochondrial ATP and telomere shortening, which may be associated with the Sirtuin 3 (SIRT3) signaling pathway. Additionally, chronic CORT injection disrupted the circadian rhythms of some indexes of aging phenotypes and altered the phase values of these indexes. Our findings suggest that psychologically stressful conditions such as depression are linked to changes in circadian rhythms and age-related phenotypes.

[Determination of thiodiglycolic acid in urine with gas chromatography-mass spectrometer].

OBJECTIVE: To establish a rapid determination method with gas chromatography-mass spectrometer (GC-MS) for thiodiglycolic acid (TDGA), a vinyl chloride (VCM) biomarker. METHODS: A high- sensitivity determination method was established using a moderate methyl esterification instead of methyl esterification of highly toxic diazo reaction. RESULTS: The standard curve regression linear equation of the method was: y=8460.5x-4758.2, the linear coefficient was 0.999 7, the minimum quantity concentration was 2.0 µg/L, the range of precision value was 0.81%-2.38%, and the average recovery of standard addition was 99.0%-102.9%. CONCLUSION: This method reduces the risk of traditional methyl esterification, improves the determination sensitivity compared with the GC-FPD method, and meets the determination requirement of TDGA.

Hypoxia Induced by Upconversion-Based Photodynamic Therapy: Towards Highly Effective Synergistic Bioreductive Therapy in Tumors.

Local hypoxia in tumors is an undesirable consequence of photodynamic therapy (PDT), which will lead to greatly reduced effectiveness of this therapy. Bioreductive pro-drugs that can be activated at low-oxygen conditions will be highly cytotoxic under hypoxia in tumors. Based on this principle, double silica-shelled upconversion nanoparticles (UCNPs) nanostructure capable of co-delivering photosensitizer (PS) molecules and a bioreductive pro-drug (tirapazamine, TPZ) were designed (TPZ-UC/PS), with which a synergetic tumor therapeutic effect has been achieved first by UC-based (UC-) PDT under normal oxygen environment, immediately followed by the induced cytotoxicity of activated TPZ when oxygen is depleted by UC-PDT. Treatment with TPZ-UC/PS plus NIR laser resulted in a remarkably suppressed tumor growth as compared to UC-PDT alone, implying that the delivered TPZ has a profound effect on treatment outcomes for the much-enhanced cytotoxicity of TPZ under PDT-induced hypoxia.

Radiation-/hypoxia-induced solid tumor metastasis and regrowth inhibited by hypoxia-specific upconversion nanoradiosensitizer.

Tumor resistance to ionizing irradiation and cancer cell's metastasis stimulated by radiation often lead to anti-cancer failure, and can be negatively caused by a key role--cellular hypoxia. In this regard, the exploitation of hypoxia-specific cytotoxic agents which assist to potentiate the anti-tumor effect of radiotherapy (RT) as well as efficiently counteract radiation-/hypoxia-induced cancer cell metastasis, becomes especially important, but has been widely overlooked. Herein, a core/shell-structured multifunctional nanoradiosensitizer with upconversion nanoparticle (UCNP) as an inside core, mesoporous silica as the shell and a cavity in between, has been constructed, in which UCNP core serves as radiation dose amplifiers and bio-reductive pro-drug--tirapazamine (TPZ) loaded in cavity is an hypoxia-selective cytotoxin and the silica shell provides the protection and diffusion path for TPZ. Such nanoradiosensitizer has been employed to inhibit the hypoxia-reoxygenation and the subsequent replication of cancer cells that often occurs after a single unaccompanied RT at low doses, and to silence the expression of transcription factors that support the progression of malignancy in cancer. This study confirms the radiotherapeutic benefits of utilizing nanoradiosensitizer as adjuvant to low-dose RT, and the results demonstrate the highly efficient hypoxia-specific killing in oxygen-dependent anti-tumor therapies.

A smart upconversion-based mesoporous silica nanotheranostic system for synergetic chemo-/radio-/photodynamic therapy and simultaneous MR/UCL imaging.

To achieve the accurate diagnosis and efficient in situ therapy of malignant tumors is encouraging but still remains a big challenge. The integration of upconversion nanoparticles and mesoporous silica that can combine the diagnostic/therapeutic functions within a single platform, may provide a more advanced way for the efficient theranostics of cancer. In this study, sub-80 nm rattle-structured multifunctional Gd-UCNPs core/mesoporous silica shell nanotheranostics (UCMSNs) were successfully constructed for the co-delivery of a radio-/photo-sensitizer hematoporphyrin (HP) and a radiosensitizer/chemodrug docetaxel (Dtxl). Upon NIR excitation and X-ray irradiation, the complete tumor elimination has been achieved by the synergetic chemo-/radio-/photodynamic tri-modal therapy under the assistance of simultaneous magnetic/upconversion luminescent (MR/UCL) bimodal imaging. To the best of our knowledge, this study is the first example of achieving tri-modal synergetic therapy in one single nanotheranostic system, and we anticipate that it may serve as a particularly useful platform for the clinical diagnosis and efficient treatment of cancer from bench to beside.

Dual-targeting upconversion nanoprobes across the blood-brain barrier for magnetic resonance/fluorescence imaging of intracranial glioblastoma.

Surgical resection, one of the main clinical treatments of intracranial glioblastoma, bears the potential risk of incomplete excision due to the inherent infiltrative character of the glioblastoma. To maximize the accuracy of surgical resection, the magnetic resonance (MR) and fluorescence imaging are widely used for the tumor preoperative diagnosis and intraoperative positioning. However, present commercial MR contrast agents and fluorescent dyes can only function for single mode of imaging and are subject to poor blood-brain barrier (BBB) permeability and nontargeting-specificity, resulting in the apparent risks of inefficient diagnosis and resection of glioblastoma. Considering the unique MR/upconversion luminescence (UCL) bimodal imaging feature of upconversion nanoparticles (UCNPs), herein, we have developed a dual-targeting nanoprobe (ANG/PEG-UCNPs) to cross the BBB, target the glioblastoma, and then function as a simultaneous MR/NIR-to-NIR UCL bimodal imaging agent, which showed a much enhanced imaging performance in comparison with the clinically used single MRI contrast (Gd-DTPA) and fluorescent dye (5-ALA). Moreover, their biocompatibility, especially to brains, was systematically assessed by the histological/hematological examination, indicating a negligible in vivo toxicity. As a proof-of-concept, the ANG/PEG-UCNPs hold the great potential in MR diagnosis and fluorescence positioning of glioblastoma for the efficient tumor surgery.

A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy.

To integrate photothermal ablation (PTA) with radiotherapy (RT) for improved cancer therapy, we constructed a novel multifunctional core/satellite nanotheranostic (CSNT) by decorating ultrasmall CuS nanoparticles onto the surface of a silica-coated rare earth upconversion nanoparticle. These CSNTs could not only convert near-infrared light into heat for effective thermal ablation but also induce a highly localized radiation dose boost to trigger substantially enhanced radiation damage both in vitro and in vivo. With the synergistic interaction between PTA and the enhanced RT, the tumor could be eradicated without visible recurrence in 120 days. Notably, hematological analysis and histological examination unambiguously revealed their negligible toxicity to the mice within a month. Moreover, the novel CSNTs facilitate excellent upconversion luminescence/magnetic resonance/computer tomography trimodal imagings. This multifunctional nanocomposite is believed to be capable of playing a vital role in future oncotherapy by the synergistic effects between enhanced RT and PTA under the potential trimodal imaging guidance.