Glycerol-weighted chemical exchange saturation transfer nanoprobes allow 19F/1H dual-modality magnetic resonance imaging-guided cancer radiotherapy.

Recently, radiotherapy (RT) has entered a new realm of precision cancer therapy with the introduction of magnetic resonance (MR) imaging guided radiotherapy systems into the clinic. Nonetheless, identifying an optimized radiotherapy time window (ORTW) is still critical for the best therapeutic efficacy of RT. Here we describe pH and O2 dual-sensitive, perfluorooctylbromide (PFOB)-based and glycerol-weighted chemical exchange saturation transfer (CEST) nano-molecular imaging probes (Gly-PFOBs) with dual fluorine and hydrogen proton based CEST MR imaging properties (19F/1H-CEST). Oxygenated Gly-PFOBs ameliorate tumor hypoxia and improve O2-dependent radiotherapy. Moreover, the pH and O2 dual-sensitive properties of Gly-PFOBs could be quantitatively, spatially, and temporally monitored by 19F/1H-CEST imaging to optimize ORTW. In this study, we describe the CEST signal characteristics exhibited by the glycerol components of Gly-PFOBs. The pH and O2 dual-sensitive Gly-PFOBs with19F/1H-CEST MR dual-modality imaging properties, with superior therapeutic efficacy and biosafety, are employed for sensitive imaging-guided lung cancer RT, illustrating the potential of multi-functional imaging to noninvasively monitor and enhance RT-integrated effectiveness.

A Study on the Efficacy of Ω Toenail Correction Treating Paronychia.

To study the clinical effects of Ω toenail correction in the treatment of paronychia. One hundred thirty-six cases of 130 patients during the period from August 2018 to August 2021 were treated with Ω toenail correction according to clinical stages, the clinical therapeutic effects of which were evaluated in terms of the operation time, the time to resume movement, treatment cycle, 1-y recurrence rate, and visual analogue scale (VAS) scores before and after treatment. The clinical efficacy was analyzed and compared of Ω toenail correction in treating paronychia of different clinical stages. It has been demonstrated that there was no significant difference in operation time, time to resume movement, treatment cycle and recurrence rate among different stages of paronychia, while there existed the significant difference (p < .05) in VAS score of resting-state pain before and after correction which stood at 6.43 ± 0.29 points with the after-treatment VAS scores at 1.10 ± 0.22. There is a statistical difference (p < .05) in VAS score of movement-evoked pain between before and after treatment. The VAS scores of movement-evoked pain stood at 7.55 ± 0.42, which is in contrast with the after-treatment VAS at 1.74 ± 0.93. It has been concluded that Ω toenail correction characterized by easy operation can relieve the pain immediately, which can achieve satisfactory clinical efficacy for treating paronychia of different stages.

Alveolar Macrophages-Mediated Translocation of Intratracheally Delivered Perfluorocarbon Nanoparticles to Achieve Lung Cancer 19F-MR Imaging.

Recent advances in intratracheal delivery strategies have sparked considerable biomedical interest in developing this promising approach for lung cancer diagnosis and treatment. However, there are very few relevant studies on the behavior and mechanism of imaging nanoparticles (NPs) after intratracheal delivery. Here, we found that nanosized perfluoro-15-crown-5-ether (PFCE NPs, ∼200 nm) exhibite significant 19F-MRI signal-to-noise ratio (SNR) enhancement than perfluorooctyl bromide (PFOB NPs) up to day 7 after intratracheal delivery. Alveolar macrophages (AMs) engulf PFCE NPs, become PFCE NPs-laden AMs, and then migrate into the tumor margin, resulting in increased tumor PFCE concentration and 19F-MRI signals. AMs-mediated translocation of PFCE NPs to lung draning lymph nodes (dLNs) decreases the background PFCE concentration. Our results shed light on the dynamic AMs-mediated translocation of intratracheally delivered PFC NPs for effective lung tumor visualization and reveal a pathway to develop and promote the clinical translation of an intratracheal delivery-based imaging strategy.

Self-assembled nanomaterials for ferroptosis-based cancer theranostics.

Most ferroptosis nanomedicines based on organic or inorganic carriers have difficulties in further clinical translation due to their serious side effects and complicated preparation. Self-assembled nanomedicines can reduce the biological toxicity caused by additional chemical modifications and excipients, offering better biocompatibility and safety. Ferroptosis therapy is an iron-associated programmed cell death dependent on lipid peroxidation with efficient tumor selectivity and biosafety. Therefore, the application of self-assembled nanomedicines with good biosafety in the ferroptosis treatment of tumors has attracted extensive attention. In this review, recent advances in the field of ferroptosis-based self-assembled nanomaterials for cancer therapy are presented, with emphasis on how these nanomaterial components interact and their distinct mechanisms for inducing ferroptosis in tumor cells, including iron metabolism, amino acid metabolism and CoQ/FSP1, as well as their respective advantages and challenges. This review would therefore help the spectrum of advanced and novice researchers interested in this area to quickly zoom in on the essential information and glean some thought-provoking ideas to advance this subfield in cancer nanomedicine.

RA-DENet: Reverse Attention and Distractions Elimination Network for polyp segmentation.

To address the problems of polyps of different shapes, sizes, and colors, low-contrast polyps, various noise distractions, and blurred edges on colonoscopy, we propose the Reverse Attention and Distraction Elimination Network, which includes Improved Reverse Attention, Distraction Elimination, and Feature Enhancement. First, we input the images in the polyp image set, and use the five levels polyp features and the global polyp feature extracted from the Res2Net-based backbone as the input of the Improved Reverse Attention to obtain augmented representations of salient and non-salient regions to capture the different shapes of polyp and distinguish low-contrast polyps from background. Then, the augmented representations of salient and non-salient areas are fed into the Distraction Elimination to obtain the refined polyp feature without false positive and false negative distractions for eliminating noises. Finally, the extracted low-level polyp feature is used as the input of the Feature Enhancement to obtain the edge feature for supplementing missing edge information of polyp. The polyp segmentation result is output by connecting the edge feature with the refined polyp feature. The proposed method is evaluated on five polyp datasets and compared with the current polyp segmentation models. Our model improves the mDice to 0.760 on the most challenge dataset (ETIS).

Peptide functionalized actively targeted MoS2 nanospheres for fluorescence imaging-guided controllable pH-responsive drug delivery and collaborative chemo/photodynamic therapy.

The combination of imaging and different therapeutic strategies into one single nanoplatform often demonstrates improved efficacy over monotherapy in cancer treatments. Herein, a multifunctional nanoplatform (labelled as MPRD) based on molybdenum disulfide quantum dots (MoS2 QDs) is developed to achieve enhanced antitumor efficiency by integrating fluorescence imaging, tumor-targeting and synergistic chemo/photodynamic therapy (PDT) into one system. First, polyethylene glycol (PEG)ylated MoS2 QDs (MP) with desirable stability are synthesized via a hydrothermal process using MoS2 QDs and carboxyamino-terminated oligomeric PEG as raw materials. Then, MP were conjugated with arginine-glycine-aspartic acid (RGD) peptide via amidation to form a novel nanocarrier (MPR), which possesses strong blue fluorescence, good biocompatibility and ανß3 receptor-mediated targeting ability. More importantly, MPR generated reactive oxygen species under 808 nm laser activation to realize targeted antitumor PDT. Further doxorubicin (DOX) was loaded onto MPR, which endows MPRD with localized chemotherapy and pH-responsive drug release. The MPRD exhibits improved chemotherapy performance on HepG2 cells (overexpressing integrin ανß3) owing to enhanced cellular uptake mediated by ανß3 receptor and effective drug release triggered by intracellular pH. Notably, MPRD with efficient tumor targeting ability and high chemo/PDT efficacy under NIR laser irradiation is capable of inhibiting HepG2 tumor cell growth both in vitro and in vivo, which is significantly superior to each individual therapy. These findings demonstrate that MPRD holds great potential in effective cancer therapy.

An efficient calcium-based sorbent for flue gas dry-desulfurization: promotion roles of nitrogen oxide and oxygen.

The development of sorbents for flue gas desulfurization in a dry mode is essential to control emission of sulfur dioxide. Based on the novel concept of "treating waste with waste", a low-cost and highly activated calcium-based sorbent (ACS) was prepared using coal fly ash, CaO and waste gypsum as the raw materials via the one-step incipient wetness impregnation method. Based on characterization using scanning electron microscopy and nitrogen adsorption-desorption, the ACS possessed a fibrous and netted structure with high porosity, which improved SO2 adsorption greatly. The SO2 adsorption capacity of ACS with coal fly ash/CaO/CaSO4 = 1/2/1 was high, up to 44.26 mg g-1, with 100% removal efficiency at 150 °C. In the absence of O2, SO2 was rapidly adsorbed on the sorbent to form CaSO3 according to in situ DRIFTS analysis, while when O2 was present in the flue gas, SO2/SO3 2- tended to be oxidized into SO4 2- species. Moreover, the presence of NO can further enhance the SO2 adsorption capacity of the ACS due to the formation of adsorbed NO2 or nitrate species with strong oxidizing properties. Therefore, the ACS can be considered as a sustainable sorbent with the advantage of employing fly ash for the removal of sulfur dioxide.

Dye-cored polylysine dendrimer as luminescent nanoplatform for imaging-guided anticancer drug delivery.

Dendrimers have numerous applications in imaging and drug delivery. Designing a dendrimer diagnostic platform with a well-defined structure and controlled drug delivery is a formidable challenge. Here, we design dendritic polymer-platinum conjugates (G5-PEG-Pt) as pH-responsive nanovesicles for imaging-guided platinum drug delivery. The G5-PEG-Pt have a well-defined structure, intrinsically bright fluorescence, and acid-responsive drug release. The pH-responsive G5-PEG-Pt could rapidly release the platinum drug at acidic pH (5.0) than neutral pH (7.4). The G5-PEG-Pt could enter SKOV-3 human ovarian cancer cells by the endocytosis pathway and exhibited comparative cytotoxicity to free cisplatin. By virtue of the prolonged blood circulation time and the enhanced permeability and retention (EPR) effect, a 4.4-fold higher tumor platinum uptake than that of free cisplatin was achieved, potentially enhancing the therapeutic indexes of the platinum drug. Therefore, these pH-responsive platinum and fluorescent dendrimer conjugates are expected to be potent in vivo cancer optical imaging and therapy platforms.

Molecularly Precise, Bright, Photostable, and Biocompatible Cyanine Nanodots as Alternatives to Quantum Dots for Biomedical Applications.

Fluorescent imaging with fluorophores has become a powerful way to explore complex biological systems and visualize nanoparticles for drug delivery. However, it is challenging to develop fluorophores with ideal physical and optical properties. We report a method to synthesize cyanine nanodots with a single-molecule structure, well-defined particle size, customizable fluorescent spectrum, and bright and stable fluorescence. These cyanine nanodots are acquired by the divergent synthesis of cyanine-dye-cored polylysine (PLL) dendrimers. We demonstrated the feasibility of the method by synthesizing cyanine 3 (Cy3), cyanine 5 (Cy5), or cyanine 7 (Cy7) cored single-molecule nanodots up to eight generations with a size of around 11 nm. We show that these cyanine nanodots are capable of multiple biomedical applications, including multicolor cellular tracing and cancer imaging. These cyanine nanodots possess many merits of organic dots and quantum dots that are promising for future application.

A near-infrared triggered upconversion/MoS2 nanoplatform for tumour-targeted chemo-photodynamic combination therapy.

The combination of photodynamic therapy and chemotherapy has shown a great potential in cancer treatment. As a promising photosensitizer, MoS2 quantum dots (QDs) have limited application due to the low tissue penetration of its light absorbing wavelength in the ultraviolet and visible regions. For the purpose of utilizing MoS2QDs in higher NIR absorption region, herein, we constructed a core/shell nano-photosensitizer upconversion@MoS2 with doxorubicin loading. This nanoplatform can convert 980 nm NIR into visible light, activating MoS2QDs to produce reactive oxygen species through fluorescence resonance energy transfer. In addition, this nanoplatform presented good biocompatibility and tumor targeting after polyethylene glycol and folic acid modification. Interestingly, with pH-responsive drug release performance, this nanoplatform presented efficient chemotherapy effects. Thus, the tumour-targeted nanoplatform can achieve up-converted luminescence imaging guided chemo-photodynamic synergistic therapy effectively.

Perfusion Analysis of Kidney Injury in Rats With Cirrhosis Induced by Common Bile Duct Ligation Using Arterial Spin Labeling MRI.

BACKGROUND: Arterial spin labeling (ASL) has been proven to be effective in ischemia-induced acute kidney injury (AKI); however, validation of ASL magnetic resonance imaging (MRI) is limited in AKI in the presence of cirrhosis. PURPOSE: To investigate the feasibility of ASL in revealing renal blood flow (RBF) changes in kidney injury in the presence of cirrhosis and to assess its value in the early diagnosis of disease. STUDY TYPE: Longitudinal. ANIMAL MODEL: Rats were randomized into baseline group (N = 3), sham surgery group (N = 18), and common bile duct ligation (BDL) group (N = 48). All groups were divided into six subgroups based on different sacrificed time points. FIELD STRENGTH/SEQUENCE: 3 T scanner, prototypic pulsed ASL sequence using flow-sensitive alternating inversion recovery preparation, half-Fourier acquisition single-shot turbo spin echo sequence. ASSESSMENT: RBF measurement was performed by ASL. Hematoxylin-eosin (HE) score, Hypoxia-inducible factor-1alpha (HIF-1α) score, peritubular capillar (PTC) density, alanine aminotransferase, aspartate aminotransferase, serum total bilirubin, total bile acids, serum creatinine (Scr), and blood urea nitrogen (BUN) were harvested. STATISTICAL TESTS: Analysis of variance, Pearson's correlation coefficient, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. RESULTS: RBF, HE score, HIF-1α score, and PTC density after BDL were significantly different from baseline. RBF was highly correlated with HE score, HIF-1α score, and PTC density (r = -0.7598, r = -0.7434, r = 0.6406, respectively). RBF and Scr began to differ significantly from baseline at day 3 and 7 after intervention, respectively. The areas under the curves of RBF, Scr, and BUN for distinguishing non-AKI from AKI in cirrhosis were 1.00, 0.888, and 0.911, while those for distinguishing mild from severe kidney injury were 0.961, 0.830, and 0.857, respectively. DATA CONCLUSION: ASL allows the longitudinal assessment of the degree of AKI induced by cholestatic cirrhosis in rats and can serve as a noninvasive marker for the early and accurate diagnosis of AKI. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Side-Chain-Type Anion Exchange Membranes Based on Poly(arylene ether sulfone)s Containing High-Density Quaternary Ammonium Groups.

To obtain anion exchange membranes with both high ionic conductivity and good dimensional stability, a series of side-chain-type poly(arylene ether sulfone)s (PAES-QDTPM-x) were designed and synthesized. Quaternary ammonium (QA) groups were densely aggregated and grafted onto the main chain via flexible hydrophobic spacers. Well-defined microphase separation was confirmed by small-angle X-ray scattering. PAES-QDTPM-0.30 exhibited reasonably high conductivity (39.4 mS cm-1 at 20 °C and 76.1 mS cm-1 at 80 °C) and excellent dimensional stability at 80 °C (11.9% in length, 11.2% in thickness) due to the concentration of ion clusters and the side-chain-type structure. All membranes maintained over 82% of the conductivity after alkali treatment for 14 days. In the H2/O2 fuel cell performance test, the maximum power density of PAES-QDTPM-0.30 at 60 °C was 225.8 mW cm-2.

IMPERFECTIVE EXINE FORMATION (IEF) is required for exine formation and male fertility in Arabidopsis.

KEY MESSAGE: IEF, a novel plasma plasma membrane protein, is important for exine formation in Arabidopsis. Exine, an important part of pollen wall, is crucial for male fertility. The major component of exine is sporopollenin which are synthesized and secreted by tapetum. Although sporopollenin synthesis has been well studied, the transportation of it remains elusive. To understand it, we analyzed the gene expression pattern in tapetal microdissection data, and investigated the potential transporter genes that are putatively regulated by ABORTED MICROSPORES (AMS). Among these genes, we identified IMPERFECTIVE EXINE FORMATION (IEF) that is important for exine formation. Compared to the wild type, ief mutants exhibit severe male sterility and pollen abortion, suggesting IEF is crucial for pollen development and male fertility. Using both scanning and transmission electron microscopes, we showed that exine structure was not well defined in ief mutant. The transient expression of IEF-GFP driven by the 35S promoter indicated that IEF-GFP was localized in plasma membrane. Furthermore, AMS can specifically activate the expression of promoterIEF:LUC in vitro, which suggesting AMS regulates IEF for exine formation. The expression of ATP-BINDING CASSETTE TRANSPORTER G26 (AGCB26) was not affected in ief mutants. In addition, SEM and TEM data showed that the sporopollenin deposition is more defective in abcg26/ief-2 than that of in abcg26, which suggesting that IEF is involved in an independent sporopollenin transportation pathway. This work reveal a novel gene, IEF regulated by AMS that is essential for exine formation.

Tuning the Brightness and Photostability of Organic Dots for Multivalent Targeted Cancer Imaging and Surgery.

Specific labeling of biomarkers with bright and high photostable fluorophores is vital in fluorescent imaging applications. Here, we report a general strategy to develop single-molecule dendritic nanodots with finely tunable optical properties for in vivo fluorescent imaging. The well-defined nanodots are based on the divergent growth of biodegradable polylysine dendrimers with a fluorophore as the core. By tuning the size and surface chemistry, we obtained fluorescent nanodots with excellent brightness and photostability, favorable pharmacokinetics, and multivalent tumor-targeting capability. The nanodots provided robust, stable, long-lasting, and specific fluorescence enhancement in tumor tissue with an in situ tumor-to-normal ratio (TNR) of ∼3 and lasting over 5 days and an ex vivo TNR up to ∼17, holding considerable promise for cancer imaging and image-guided surgery. This strategy significantly improves the in vivo performance of fluorophores and can be applied to other modality imaging probes.

Polyhydroxylated sterols from Monascus purpureus-fermented rice.

Using a cell-based cytotoxicity assay, two new polyhydroxylated sterols, 16(S),22(S)-epoxy-3ß,5α,6ß,20(R),23(R),25-hexahydroxy-7-ergostene and 3ß,7ß,8α,25-tetrahydroxy-5,22E-ergostadiene were isolated from the ethyl acetate portion of the ethanolic extract of Monascus purpureus. Their structures were elucidated by spectroscopic analysis and in comparison with those reported in the literature. Both compounds showed cytotoxic activity against the lung adenocarcinoma (A549) with IC50 values of 12.6 and 18.5 µM, exhibited moderate activities against human ovarian cancer (A2780), with IC50 values of 8.8 and 9.4 µM.