Improved Diagnostic Accuracy of Multi-Slice Spiral CT Combined with MRI in Colon Cancer Patients with Ileus: A Comparative Study.

Background: Colon cancer is a common malignant tumor that often leads to intestinal obstruction, resulting in significant morbidity and mortality. Early and accurate diagnosis of colon cancer and associated ileus is crucial for timely treatment and improved patient outcomes. Various diagnostic methods, including MSCT and MRI, are currently used in clinical practice. However, the optimal imaging approach for accurate diagnosis remains uncertain. Objective: To study the value and accuracy of multi-slice spiral CT (MSCT) combined with magnetic resonance imaging (MRI) in diagnosing colon cancer obstruction. Methods: A retrospective analysis was performed on 100 cases of colon cancer and ileus patients admitted to the Hai'an Hospital of Chinese Medicine from January 2019 to July 2020. The cases were randomly divided into control and experimental groups, with 50 cases in each. The control group was diagnosed with MSCT, and the experimental group was diagnosed with MRI based on the control group. The positive and negative detection rates, test accuracy, sensitivity, and specificity were compared between the 2 groups. The area under the curve (AUC), quality of life (QOL) score, and mental status scale in non-psychiatric settings (MSSNS) score were calculated with the receiver operator characteristic curve (ROC) and compared between the 2 groups. Results: The test accuracy, positive detection rate, negative detection rate, test specificity, sensitivity, and AUC of the experimental group were significantly higher than those of the control group, and the results were statistically significant (P < .05). There was no significant difference in the QOL and the MSSNS scores between the 2 groups (P > .05). Conclusion: MSCT combined with MRI has a high application value in diagnosing colon cancer obstruction patients, and can significantly improve the test's accuracy, specificity and sensitivity.

Tailored Trojan horse nanocarriers for enhanced redox-responsive drug delivery.

Redox-responsive anti-tumor nanomedicine is appealing in improving the therapeutic efficacy and patient compliance. However, the thiol-disulfide exchange reaction is reversible and kinetically very slow, resulting in poor drug release and delayed onset of drug action. To address this issue, a tailored Trojan horse nanocarrier is designed with pH-labile zeolitic imidazolate framework-8 (ZIF-8) as the core and disulfide-linked amphiphilic polymer-drug conjugate as the steric shell. A potent reductant, tris(3-hydroxypropyl)phosphine (THPP) is loaded in ZIF-8 and capped by myristyl alcohol. At low pH (e.g. endosome and lysosome), the collapse of ZIF-8 can induce the liberation of THPP that further cleaves the disulfide bond and release the drug post self-immolation. As the reaction between THPP and disulfide is both thermodynamically and kinetically favored, the drug release rate can be boosted. The proof-of-concept is demonstrated both in 4T1 murine mammary carcinoma cells and 4T1 tumor-bearing mice with curcumin as the model drug. Compared to the control nanosystem without THPP, the tailored nanocarrier can significantly enhance the drug release and hence therapeutic efficacy, which is demonstrated by the assays of cell viability, tumor growth inhibition, and histological staining. Such strategy can extend to a plethora of thiol-free cargos for controlled intracellular delivery.

Electron-Accepting Micelles Deplete Reduced Nicotinamide Adenine Dinucleotide Phosphate and Impair Two Antioxidant Cascades for Ferroptosis-Induced Tumor Eradication.

Ferroptotic antitumor therapy has been compromised by various intracellular antioxidants, particularly glutathione and thioredoxin. Both are cofactors of glutathione peroxide 4 (GPX4) that act against oxidative stress via catalyzing the reduction of lipid peroxides. It was postulated that tailored polymer micelles could enhance ferroptotic antitumor efficacy via diminishing glutathione and thioredoxin under hypoxia. The aim was to engineer hypoxia-responsive micelles for selective enhancement of ferroptotic cell death in solid tumor. The polymer contains hydrophilic poly(ethylene glycol) (PEG) that is linked by azobenzene linker with nitroimidazole-conjugated polypeptide. The tailored polymer could self-assemble into nanoscale micelles to encapsulate RAS-selective lethal small molecule 3, a covalent GPX4 inhibitor. Under hypoxia, the azobenzene moiety enabled PEG shedding and enhanced micelles uptake in 4T1 cells. Likewise, the nitroimidazole moiety was reduced by the overexpressed nitroreductase with reduced nicotinamide adenine dinucleotide phosphate (NADPH) as the cofactor, resulting in transient depletion of NADPH. This impaired both the glutathione and thioredoxin redox cycle, leading to diminished intracellular glutathione and thioredoxin. The selective potency of ferroptotic micelles in depleting NADPH, glutathione and thioredoxin was further verified in vivo in the 4T1 tumor xenograft mice model. This work highlights the role of hypoxia-responsive polymers in enhancing the potency of ferroptotic inducers against solid tumors without additional side effects to healthy organs.

Upconverting Nanocarriers Enable Triggered Microtubule Inhibition and Concurrent Ferroptosis Induction for Selective Treatment of Triple-Negative Breast Cancer.

Despite the resistance of triple-negative breast cancer (TNBC) to targeted hormone therapy, the discovery of azobenzene combretastatin A4 (Azo-CA4) provides therapeutic opportunities for TNBC. Here, Azo-CA4 was loaded in upconverting nanocarriers that could convert near-infrared (NIR) light to UV light to activate Azo-CA4. Upon irradiation, Azo-CA4-loaded nanocarriers significantly reduced the viability of TNBC cells via both apoptosis and ferroptosis. The former was induced by photoisomerization of Azo-CA4, accompanied by microtubule breakdown and cell cycle arrest at G2/M phase. The latter was caused by the UV light-induced reduction of Fe3+ to Fe2+ that facilitates the peroxidation of tailored lipids. The cooperation between apoptosis and ferroptosis in eliminating TNBC was demonstrated in a xenograft mice model in terms of histological staining, tumor growth inhibition, and animal survival. Since the NIR light is only applied to the tumor site, the adverse effects of such triggered nanocarriers to the healthy organs are negligible.

Triggered All-Active Metal Organic Framework: Ferroptosis Machinery Contributes to the Apoptotic Photodynamic Antitumor Therapy.

Nanoscale photodynamic therapy (PDT) is an appealing antitumor modality for which apoptosis is the major mechanism of toxicity induction. It was postulated that the highly reactive singlet oxygen in PDT could deplete glutathione (GSH) and activate ferroptosis, the extent to which could be further manipulated by a redox-responsive nanocarrier. To validate this, a disulfide-bearing imidazole ligand coordinated with zinc to form an all-active metal organic framework (MOF) nanocarrier where a photosensitizer (chlorin e6/Ce6) was encapsulated. Regardless of light irradiation, the Ce6-loaded nanocarrier caused the depletion of intracellular GSH via the disulfide-thiol exchange reaction in a murine mammary carcinoma cell line (4T1). The GSH depletion further caused the inactivation of glutathione peroxide 4 (GPX4) and the enhancement of cytotoxicity that was alleviated by ferroptosis inhibitors. The superior in vivo antitumor efficacy of the all-active nanocarrier was corroborated in a 4T1 tumor-bearing mice model regarding tumor growth suppression and animal survival rate. The coadministration of an iron chelator weakened the antitumor potency of the nanocarrier due to ferroptosis inhibition, which was supported by the fact of tumor growth upsurge and the recovered GPX4 activity. The current work highlights the contribution of ferroptotic machinery to antitumor PDT via an activatable, adaptable, all-active MOF nanocarrier.

Energy-Free, Singlet Oxygen-Based Chemodynamic Therapy for Selective Tumor Treatment without Dark Toxicity.

Traditional singlet oxygen-based antitumor therapies have been burdened with the necessity of external energy (e.g., light and ultrasound) and harmful dark toxicity. Ascorbate at the pharmacological concentration could accumulate hydrogen peroxide only in the tumor site. It is postulated that the concurrent delivery of ascorbate and nanoparticulate hypochlorous ion (ClO- ) could produce singlet oxygen at the tumor site as an energy-free, tumor-specific therapy. The ClO- is loaded in a hybrid core-shell nanocarrier consisting of a zeolitic imidazolate framework and amphiphilic poloxamer 188. Intracellular singlet oxygen production is verified in 4T1 cells by the cooperation between hybrid nanocarriers and ascorbate, which induces significant apoptotic cell death. Upon intravenous nanocarriers delivery plus intraperitoneal ascorbate administration to xenograft mice, the in vivo antitumor efficacy of this cooperative nanomedicine is demonstrated without noticeable side-effects. This work demonstrates a proof-of-concept of singlet oxygen-based chemodynamic therapy for selective tumor eradication, which produces a novel trigger-free, singlet oxygen-based cancer therapy without the side effects of traditional photodynamic and sonodynamic therapy.

Gated Mesoporous Silica Nanocarriers for Hypoxia-Responsive Cargo Release.

Mesoporous silica nanocarriers (MSNs) are appealing in terms of their large cavity surface area and high loading capacity, but they have been suffering from premature cargo release. Herein, we report a gated smart MSN that is sensitive to low oxygen concentration (i.e., hypoxia) via taking advantage of the superior electron-accepting ability of the azobenzene moiety. The azobenzene polymer was employed as the responsive gate-keeper that was deposited on the MSN surface, followed by coating with amphiphilic Pluronic F68 for steric stabilization. The obtained nanocarriers were less than 200 nm. The in vitro polymer degradation was spectrophotometrically witnessed via the employment of a reducing agent, namely, sodium dithionite, with a strong electron-donating ability. The hypoxia-responsive cargo release from the gated MSN was quantitatively demonstrated in breast cancer cells (MCF-7) using the fluorescence resonance energy transfer (FRET) technique where coumarin 6 and rhodamine B was selected as the FRET donor and acceptor, respectively. The FRET ratio was used as the index and decreased linearly over time under hypoxia, whereas it almost remained steady under normoxia. In addition, a model photosensitizer, namely, chlorin e6, was also loaded in the gated MSN whose toxicity under hypoxia was verified. This study developed a hypoxia-responsive MSN with the azobenzene polymer as the removable gate-keeper, which would expand the application of MSNs in pharmaceutical and biomedical areas since the low oxygen concentration is a unique trigger in many pathological conditions.

Supercritical carbon dioxide extract of Cinnamomum cassia bark: toxicity and repellency against two stored-product beetle species.

The extract from Cinnamomum cassia Presl bark was obtained with supercritical CO2 fluid extraction (SFE). Chemical components of the SFE extract were characterized by GC-MS spectrometry. The repellency and contact toxicity of the SFE extract were evaluated against the adults of Tribolium castaneum and Lasioderma serricorne along with those of its two main compounds. The results of GC-MS analysis indicated that 33 volatile constituents were identified from the extract. The main components included trans-cinnamaldehyde (32.1%), 3,3-dimethylhexane (10.6%) and 2,4-di-tert-butylphenol (7.9%). Testing results showed that the SFE extract had potent contact toxicity against T. castaneum and L. serricorne with LD50 values of 3.96 and 23.89 µg/adult, respectively. LD50 values of trans-cinnamaldehyde against T. castaneum and L. serricorne were 5.78 and 3.24 µg/adult, respectively. Additionally, percentage repellency values of the SFE extract and trans-cinnamaldehyde against T. castaneum and L. serricorne were rather high (PR = 100% and PR > 90%, respectively) at 78.63 and 15.73 nL/cm2 at 2 h post-exposure. 2,4-Di-tert-butylphenol showed some repellency against both beetle species. Considering its insecticidal and repellent effects, the SFE extract from C. cassia bark might be used in integrated pest management programs for T. castaneum and L. serricorne.

Effects of different mixing ratios on emissions from passenger cars fueled with methanol/gasoline blends.

Regulated and unregulated emissions from four passenger cars fueled with methanol/gasoline blends at different mixing ratios (M15, M20, M30, M50, M85 and M100) were tested over the New European Driving Cycle (NEDC). Volatile organic compounds (VOCs) were sampled by Tenax TA and analyzed by thermal desorption-gas chromatograph/mass spectrometer (TD-GC/MS). Carbonyls were trapped on dinitrophenylhydrazine (DNPH) cartridges and analyzed by high performance liquid chromatography (HPLC). The results showed that total emissions of VOCs and BTEX (benzene, toluene, ethylbenzene, p, m, o-xylene) from all vehicles fueled with methanol/gasoline blends were lower than those from vehicles fueled with only gasoline. Compared to the baseline, the use of M85 decreased BTEX emissions by 97.4%, while the use of M15 decreased it by 19.7%. At low-to-middle mixing ratios (M15, M20, M30 and M50), formaldehyde emissions showed a slight increase while those of high mixing ratios (M85 and M100) were three times compared with the baseline gasoline only. When the vehicles were retrofitted with new three-way catalytic converters (TWC), emissions of carbon monoxide (CO), total hydrocarbon (THC), and nitrogen oxides (NO(x)) were decreased by 24%-50%, 10%-35%, and 24%-58% respectively, compared with the cars using the original equipment manufacture (OEM) TWC. Using the new TWC, emissions of formaldehyde and BTEX were decreased, while those of other carbonyl increased. It is necessary that vehicles fueled with methanol/gasoline blends be retrofitted with a new TWC. In addition, the specific reactivity of emissions of vehicles fueled with M15 and retrofitted with the new TWC was reduced from 4.51 to 4.08 compared to the baseline vehicle. This indicates that the use of methanol/gasoline blend at a low mixing ratio may have lower effect on environment than gasoline.