Design and Evaluation of 3-Phenyloxetane Derivative Agonists of the Glucagon-Like Peptide-1 Receptor.

Various small molecule GLP1R agonists have been developed and tested for treating type 2 diabetes (T2DM) and obesity. However, many of these new compounds have drawbacks, such as potential hERG inhibition, lower activity compared to natural GLP-1, limited oral bioavailability in cynomolgus monkeys, and short duration of action. Recently, a new category of 3-phenyloxetane derivative GLP1R agonists with enhanced hERG inhibition has been discovered. Using an AIDD/CADD method, compound 14 (DD202-114) was identified as a potent and selective GLP1R agonist, which was chosen as a preclinical candidate (PCC). Compound 14 demonstrates full agonistic efficacy in promoting cAMP accumulation and possesses favorable drug-like characteristics compared to the clinical drug candidate Danuglipron. Additionally, in hGLP-1R knock-in mice, compound 14 displayed a sustained pharmacological effect, effectively reducing blood glucose levels and food intake. These findings suggest that compound 14 holds promise as a future treatment option for T2DM and obesity, offering improved properties.

Enhanced the energy conversion of corn stalk via co-production of photo-fermentation biohydrogen and bioethanol.

Hydrogen-ethanol co-production can significantly improve the energy conversion efficiency of corn stalk (CS). In this study, with CS as the raw material, the co-production characteristics of one-step and two-step photo-fermentation hydrogen production (PFHP) and ethanol production were investigated. In addition, the gas and liquid characteristics of the experiment were analyzed. The kinetics of hydrogen-ethanol co-production was calculated, and the economics of hydrogen and ethanol were analyzed. Results of the experiments indicated that the two-step hydrogen-ethanol co-production had the best hydrogen production performance when the concentration of CS was 25 g/L. The total hydrogen production was 350.08 mL, and the hydrogen yield was 70.02 mL/g, which was 2.45 times higher than that of the one-step method. The efficiency of hydrogen-ethanol co-production was 17.79 %, which was 2.76 times more efficient than hydrogen compared to fermentation with hydrogen. The result provides technical reference for the high-quality utilization of CS.

A laponite-based immunologically active gel delivery system for long-acting tumor vaccine.

Traditional bolus vaccines typically require multiple doses, which complicates the vaccination process and may cause missed shots, leading to sub-optimal immunity and reduced vaccine effectiveness. Herein, a gel-based long-acting vaccine system with self-adjuvant properties based on laponite was constructed to simplify vaccination procedures and improve vaccine effectiveness. Firstly, the gel system could recruit multiple types of immune cells to form immune niches. Secondly, it could achieve sustained delivery of antigens to lymph nodes by active transport and passive drainage. Then, the gel system triggered the formation of a large number of germinal centers, which elicited enhanced and durable humoral immune responses, as well as strong cellular immune responses. As a result, it eventually showed good prophylactic and therapeutic effects in a variety of tumor models including melanoma, colorectal cancer and peritoneal metastasis models. By further combining the immunoadjuvant CpG ODN and cytokine IL-12, the effect of the gel-vaccine could be further enhanced. In a murine peritoneal metastasis model of colorectal carcinoma, a single administration of the gel-vaccine resulted in complete tumor eradication in 8/9 mice. In summary, this study developed an immunologically active gel-vaccine system. And as a robust and versatile vaccine platform, by loading different antigens and adjuvants, this gel-vaccine system is expected to realize its better therapeutic potential.

Quercetin inhibits the epithelial-mesenchymal transition and reverses CDK4/6 inhibitor resistance in breast cancer by regulating circHIAT1/miR-19a-3p/CADM2 axis.

Breast cancer (BC) cells have a high risk of metastasis due to epithelial-mesenchymal transition (EMT). Palbociclib (CDK4/6 inhibitor) is an approved drug for BC treatment. However, the drug resistance and metastasis can impair the treatment outcome of Palbociclib. Understanding the mechanisms of EMT and Palbociclib drug resistance in BC is conducive to the formulation of novel therapeutic strategy. Here, we investigated the role of circHIAT1/miR-19a-3p/CADM2 axis in modulating EMT and Palbociclib resistance in BC. circHIAT1 and CADM2 were down-regulated in BC tissues and cell lines, and miR-19a-3p showed an up-regulation. circHIAT1 could interact with miR-19a-3p and suppress its activity, while miR-19a-3p functioned to negatively regulate CADM2. Forced over-expression of circHIAT1 could impaired the EMT status and migratory ability of BC cells, and this effect was inhibited by miR-19a-3p mimic. In addition, we also generated Palbociclib resistant BC cells, and showed that circHIAT1 and CADM2 were down-regulated in the resistant BC cells while miR-19a-3p showed an up-regulation. Forced circHIAT1 over-expression re-sensitized BC cells to Palbociclib treatment. Quercetin, a bioactive flavonoid, could suppressed the migration and invasion of BC cells, and re-sensitized BC cells to Palbociclib. The anti-cancer effect of quercetin could be attributed to its regulatory effect on circHIAT1/miR-19a-3p/CADM2 axis. In vivo tumorigenesis experiment further revealed that quercetin administration enhanced the anti-cancer effect of Palbociclib, an effect was dependent on the up-regulation of circHIAT1 by quercetin. In summary, this study identified quercetin as a potential anti-cancer compound to reverse Palbociclib resistance and impair EMT in BC cells by targeting circHIAT1/miR-19a-3p/CADM2 axis.

Copper Single-Atom-Based Metal-Organic Framework for Ultrasound-Enhanced Nanocatalytic Therapy.

Chemodynamic therapy (CDT) is an emerging therapeutic modality triggered by endogenous substances in the tumor microenvironment (TME) to generate reactive oxygen species. However, the mild acid pH, low H2O2 concentration, and overexpressed glutathione can suppress the CDT efficiency. Herein, ultrasound (US)-triggered Cu2+-based single-atom nanoenzymes (FA-NH2-UiO-66-Cu, FNUC) are constructed with the performance of target and glutathione depletion. In the TME, the single-atom Cu sites of FNUC consume glutathione and the FNUC:Cu+ generates •OH via peroxidase-like activity. The US-activated FNUC exhibits a fast •OH generation rate, a low Michaelis constant, and a large •OH concentration, indicating the cavitation effect of US promotes the •OH generation. Meanwhile, the tumor target of FNUC is confirmed by NIR-II fluorescence imaging, in which it is modified with IR-1061. Combined with the antitumor performance of FNUC in vitro and in vivo, the novel Cu-based SAzymes can achieve efficient and precise cancer treatment.

Mitoxantrone Combined with Engineered TRAIL-Nanovesicles for Enhanced Cancer Immunotherapy Via Converting Apoptosis into Pyroptosis.

Pyroptosis, a highly inflammatory form of programmed cell death, has emerged as a promising target for cancer immunotherapy. However, in the context of pyroptosis execution, while both caspase-3 and GSDME are essential, it is noteworthy that GSDME is frequently under-expressed in cold tumors. To overcome this limitation, engineered cellular nanovesicles (NVs) presenting TRAIL on their membranes (NVTRAIL) are developed to trigger the upregulation of cleaved caspase-3. When strategically combined with the chemotherapeutic agent mitoxantrone (MTO), known for its ability to enhance GSDME expression, MTO@NVTRAIL can convert cancer cells from apoptosis into pyroptosis, inhibit the tumor growth and metastasis successfully in primary tumor. The microparticles released by pyroptotic tumor cells also exhibited certain cytotoxicity against other tumor cells. In addition, tumor cells exposed to the combination treatment of MTO@NVTRAIL in vitro have also demonstrated potential utility as a novel form of vaccine for cancer immunotherapy. Flow analysis of the tumor microenvironment and draining lymph nodes reveals an increased proportion of matured dendritic cells and activation of T cells. In summary, the research provided a reference and alternative approach to induce cancer pyroptosis for clinical antitumor therapy based on engineered cellular nanovesicles and chemotherapy.

Temporary mechanical circulatory support as a bridge to durable left ventricular assist device as destination therapy in fulminant giant cell myocarditis：A case report.

Fulminant giant cell myocarditis is a fatal form of acute myocarditis leading to a rapid-onset clinical presentation with lethal arrhythmias, acute heart failure, or cardiogenic shock requiring mechanical circulatory support. We report the case of a 52-year-old female diagnosed with fulminant myocarditis requiring veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and intra-aortic balloon pump(IABP) support. Due to hemodynamic instability, she was transferred to our hospital by helicopter on day 4. On arrival at our hospital, she underwent percutaneous balloon atrial septostomy to decompress the left ventricle. Although the left ventricular distension and pulmonary edema improved after atrial septostomy, no signs of biventricular function recovery were identified on day 14. On day 23, V-A ECMO and IABP were switched to a durable left ventricular assist device(LVAD) system and a right ventricular assist device(RVAD) with ECMO (RVAD-ECMO) under median sternotomy. On day 37, RVAD-ECMO was eventually removed and rehabilitation was started with the remaining LVAD support as destination therapy. On day 78, the patient was finally discharged with LVAD support to follow-up as an outpatient. This case underscores the importance of a multidisciplinary approach and rigorous monitoring to optimize outcomes in the treatment of fulminant giant cell myocarditis.

Complete mitochondrial genome of Melia azedarach L., reveals two conformations generated by the repeat sequence mediated recombination.

Melia azedarach is a species of enormous value of pharmaceutical industries. Although the chloroplast genome of M. azedarach has been explored, the information of mitochondrial genome (Mt genome) remains surprisingly limited. In this study, we used a hybrid assembly strategy of BGI short-reads and Nanopore long-reads to assemble the Mt genome of M. azedarach. The Mt genome of M. azedarach is characterized by two circular chromosomes with 350,142 bp and 290,387 bp in length, respectively, which encodes 35 protein-coding genes (PCGs), 23 tRNA genes, and 3 rRNA genes. A pair of direct repeats (R1 and R2) were associated with genome recombination, resulting in two conformations based on the Sanger sequencing and Oxford Nanopore sequencing. Comparative analysis identified 19 homologous fragments between Mt and chloroplast genome, with the longest fragment of 12,142 bp. The phylogenetic analysis based on PCGs were consist with the latest classification of the Angiosperm Phylogeny Group. Notably, a total of 356 potential RNA editing sites were predicted based on 35 PCGs, and the editing events lead to the formation of the stop codon in the rps10 gene and the start codons in the nad4L and atp9 genes, which were verified by PCR amplification and Sanger sequencing. Taken together, the exploration of M. azedarach gap-free Mt genome provides a new insight into the evolution research and complex mitogenome architecture.

Classic congenital adrenal hyperplasia with unilateral functional adrenal cortical adenoma: case report.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders related to adrenal steroid biosynthesis, and mainly caused by mutations in the CYP21A2 gene encoding 21-hydroxylase. Adrenal tumors are common in CAH, but functional adrenal tumors are rare. Here, we report a 17-year-old female with virilized external genitalia and primary amenorrhea, accompanied by a right adrenal tumor. Her 17-OHP level was normal, cortisol and androgen levels were significantly elevated, and the tumor pathology showed adrenal cortical adenoma. Gene testing for CYP21A2 showed c.518T > A in exon 4 and c.29313C > G in intron 2. The possibility of untreated classic CAH with 21-OH deficiency causing functional adrenal cortical adenoma should be considered. When clinical diagnosis highly considers CAH and cannot rule out the influence of functional adrenal tumors' secretion function on 17-OHP, gene mutation analysis should be performed.

Development and application of a CNT-Ag-Cu-Al/PS-based paper electrode for detecting diverse analytes in complex matrices.

Electrochemical sensors play a crucial role in the detection of different analytes in complex matrices, and their performance is highly dependent on the electrode capacity. However, most of the available electrodes can only be used for single-component detection, so it is urgent to develop electrodes with high sensitivity and selectivity for different components. Herein, we report an amphiprotic amino-bonded carbon nanotube-Ag/Cu/Al nanoparticle/polystyrene-coated paper electrode (CNT-Ag-Cu-Al/PS electrode), which can be used for the measurement of glucose (Glc), oxytetracycline (OTC), and hydroquinone (HQ), respectively. The results showed that the analytical sensitivity and selectivity of the CNT-Ag-Cu-Al/PS electrode were comparable to those of single metal-coated paper substrate. The developed electrode also exhibited excellent linear responses for Glc, OTC, and HQ in the ranges of 1.0-1000.0 µM, 1.0 × 10-2 to 10.0 µM, and 5.0 × 10-3 to 50.0 µM, and the limits of detection (LODs) were 0.2055 µM (Glc), 0.0074 µM (OTC), and 0.0048 µM (HQ). Owing to the characteristics of good selectivity, anti-interference, stability, and reproducibility, the CNT-Ag-Cu-Al/PS paper electrode has been successfully applied to the detection of these analytes in complex human body fluids, food, and environmental waters. The paper electrode is promising for the detection of target compounds in complex matrices.

Spirohypertones A and B as potent antipsoriatics: Tumor necrosis factor-α inhibitors with unprecedented chemical architectures.

Tumor necrosis factor-α (TNF-α) is a promising target for inflammatory and autoimmune diseases. Spirohypertones A (1) and B (2), two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons, were isolated from Hypericum patulum. The structures of 1 and 2 were confirmed through comprehensive spectroscopic analysis, single-crystal X-ray diffraction and electronic circular dichroism calculations. Importantly, 2 showed remarkable TNF-α inhibitory activity, which could protect L929 cells from death induced by co-incubation with TNF-α and actinomycin D. It also demonstrated the ability to suppress the inflammatory response in HaCaT cells stimulated with TNF-α. Notably, in an imiquimod-induced psoriasis murine model, 2 restrained symptoms of epidermal hyperplasia associated with psoriasis, presenting anti-inflammatory and antiproliferative effects. This discovery positions 2 as a potent TNF-α inhibitor, providing a promising lead compound for developing an antipsoriatic agent.

Paper-in-Tip Bipolar Electrospray Mass Spectrometry for Real-Time Chemical Reaction Monitoring.

Capturing short-lived intermediates at the molecular level is key to understanding the mechanism and dynamics of chemical reactions. Here, we have developed a paper-in-tip bipolar electrolytic electrospray mass spectrometry platform, in which a piece of triangular conductive paper incorporated into a plastic pipette tip serves not only as an electrospray emitter but also as a bipolar electrode (BPE), thus triggering both electrospray and electrolysis simultaneously upon application of a high voltage. The bipolar electrolysis induces a pair of redox reactions on both sides of BPE, enabling both electro-oxidation and electro-reduction processes regardless of the positive or negative ion mode, thus facilitating access to complementary structural information for mechanism elucidation. Our method enables real-time monitoring of transient intermediates (such as N,N-dimethylaniline radical cation, dopamine o-quinone (DAQ) and sulfenic acid with half-lives ranging from microseconds to minutes) and transient processes (such as DAQ cyclization with a rate constant of 0.15 s-1). This platform also provides key insights into electrocatalytic reactions such as Fe (III)-catalyzed dopamine oxidation to quinone species at physiological pH for neuromelanin formation.

Radiation-based immunogenic vaccine combined with a macrophage "checkpoint inhibitor" for boosting innate and adaptive immunity against metastatic colon cancers.

Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors. Especially, X-ray- induced dying tumor cells are rich in highly immunogenic tumor-associated antigens and self-generated dsDNA as potent adjuvants. However, we found that the X-ray induction process can result in the excessive exposure of phosphatidylserine in cancer vaccines, which can specifically bind with the MerTK receptor on macrophages, acting as a "checkpoint" to facilitate immune silence in the tumor microenvironment. Therefore, we developed a novel strategy combining X-ray-induced cancer vaccines with UNC2250, a macrophage MerTK "checkpoint inhibitor," for treating peritoneal carcinomatosis in colon cancer. By incorporating UNC2250 into the treatment regimen, immunosuppressive efferocytosis of macrophages, which relies on MerTK-directed recognition of phosphatidylserine on vaccines, was effectively blocked. Consequently, the immune analysis revealed that this combination strategy promoted the maturation of dendritic cells and M1-like repolarization of macrophages, thereby simultaneously eliciting robust adaptive and innate immunity. This innovative approach utilizing X-ray-induced vaccines combined with a checkpoint inhibitor may provide valuable insights for developing effective cancer vaccines and immunotherapies targeting colon cancer.

Biological fermentation pilot-scale systems and evaluation for commercial viability towards sustainable biohydrogen production.

Featuring high caloric value, clean-burning, and renewability, hydrogen is a fuel believed to be able to change energy structure worldwide. Biohydrogen production technologies effectively utilize waste biomass resources and produce high-purity hydrogen. Improvements have been made in the biohydrogen production process in recent years. However, there is a lack of operational data and sustainability analysis from pilot plants to provide a reference for commercial operations. In this report, based on spectrum coupling, thermal effect, and multiphase flow properties of hydrogen production, continuous pilot-scale biohydrogen production systems (dark and photo-fermentation) are established as a research subject. Then, pilot-scale hydrogen production systems are assessed in terms of sustainability. The system being evaluated, consumes 171,530 MJ of energy and emits 9.37 t of CO2 eq when producing 1 t H2, and has a payback period of 6.86 years. Our analysis also suggests future pathways towards effective biohydrogen production technology development and real-world implementation.

The Suitable Population for Opportunistic Low Bone Mineral Density Screening Using Computed Tomography.

Objective: To explore the suitable population of CT value for predicting low bone mineral density (low-BMD). Methods: A total of 1268 patients who underwent chest CT examination and DXA within one-month period retrospectively analyzed. The CT attenuation values of trabecular bone were measured in mid-sagittal plane from thoracic vertebra 7 (T7). Receiver operating characteristic (ROC) curves were used to evaluate the ability to diagnose low-BMD. Results: The AUC for diagnosing low BMD was larger in women than in men (0.894 vs 0.744, p < 0.05). The AUC increased gradually with the increase of age but decreased gradually with the increase in height and weight (p < 0.05). In females, when specificity was adjusted to approximately 90%, a threshold of 140.25 HU has a sensitivity of 69.3%, which is higher than the sensitivity of 36.5% in males for distinguishing low-BMD from normal. At the age of 70 or more, when specificity was adjusted to approximately 90%, a threshold of 126.31 HU has a sensitivity of 76.1%, which was higher than that of other age groups. Conclusion: For patients who had completed chest CTs, the CT values were more effective in predicting low-BMD in female, elderly, lower height, and lower weight patients.

Antecubital vein combined with femoral vein pathway could shorten the learning curve of simultaneous bilateral adrenal vein sampling.

During our previous bilateral adrenal vein sampling (AVS) procedure, the authors observed that accessing the left adrenal vein through the antecubital vein was more feasible than the conventional femoral vein. Meanwhile, the femoral vein pathway facilitated access to the right adrenal vein than the antecubital vein pathway. Therefore, the authors hypothesized that simultaneous bilateral AVS via the antecubital combined with the femoral vein pathway could improve the success rate. A total of 94 cases of AVS via the antecubital combined with the femoral vein pathway were performed, while the remaining 20 cases employed the antecubital vein pathway at our center between August 2020 and April 2023. Furthermore, a meta-analysis was conducted in this study using 15 selected articles to determine the success rate of AVS in each center and pathway. The success rate of ACTH-stimulated simultaneous bilateral AVS via the antecubital vein combined with the femoral vein pathway was 92.85% (P = .503) on the right and 95.00% (P < .001) on the left. In the antecubital vein pathway, the success rates were only 25.00% (P < .001) on the right side and 80.00% (P = .289) on the left side. The results of meta-analysis demonstrated a success rate of 78.16% on the right and 94.98% on the left for ACTH-stimulated AVS via the femoral vein pathway. Based on our center's experience, simultaneous bilateral adrenal vein sampling via the combined pathway could improve the success rate of AVS in the short term and shorten the learning curve.

Comparative chloroplast genomes of Argentina species: genome evolution and phylogenomic implications.

The genus Argentina Hill belongs to the tribe Potentilleae Sweet and contains approximately 75 species predominantly distributed in the Sino-Himalayan region and the Malesian archipelago. So far we have less knowledge on the phylogenetic relationships within Argentina owing to limited sampling of Argentina taxa or gene fragments in previous studies. Moreover, to date there is no phylogenetic study on Argentina from the perspective of comparative chloroplast (cp) genomics. Here we performed comparative genomic analyses on the cp genomes of 39 accessions representing 18 taxa of Argentina. The Argentina cp genomes presented the typical quadripartite structure, with the sizes ranging from 155 096 bp to 157 166 bp. The 39 Argentina cp genomes contained a set of 112 unique genes, comprising four ribosomal RNA (rRNA) genes, 30 transfer RNA (tRNA) genes, as well as 78 protein-coding genes (PCGs). The cp genome organization, gene content and order in Argentina were highly conserved, but some visible divergences were present in IR/SC boundary regions. Ten regions (trnH-GUG-psbA, trnG-GCC-trnfM-CAU, trnD-GUC-trnY-GUA, rpl32-trnL-UAG, atpH-atpI, rps16-trnQ-UUG, trnS-GCU-trnG-UCC, ndhF-rpl32, trnR-UCU-atpA, and accD-psaI) were identified as excellent candidate DNA markers for future studies on species identification, population genetics and phylogeny of Argentina. Our results indicated that Argentina is monophyletic. In the current sampling, the A. smithiana - A. anserina clade was sister to the remainder of Argentina. Our results corroborated the previous taxonomic treatments to transfer A. phanerophlebia and A. micropetala from the genus Sibbaldia L. to Argentina. Our results showed close relationships among A. stenophylla, A. microphylla, A. taliensis, and A. tatsienluensis, congruent with previous studies based on the morphology of these species. Twenty-six genes (rps3, rps15, rps16, rps19, rpl16, rpl20, rpl22, rpoA, rpoB, rpoC1, rpoC2, atpA, atpF, psbB, psbF, ndhA, ndhB, ndhC, ndhD, ndhF, rbcL, accD, ccsA, matK, ycf1, ycf2) were with sites under positive selection, and adaptive evolution of these genes might have played crucial roles in Argentina species adaptation to the harsh mountain environment. This study will facilitate future work on taxonomy, phylogenetics, and adaptive evolution of Argentina.

Colon Targeting pH-Responsive Coacervate Microdroplets for Treatment of Ulcerative Colitis.

Ulcerative colitis (UC), an immune-mediated chronic inflammatory disease, drastically impacts patients' quality of life and increases their risk of colorectal cancer worldwide. However, effective oral targeted delivery and retention of drugs in colonic lesions are still great challenges in the treatment of UC. Coacervate microdroplets, formed by liquid-liquid phase separation, are recently explored in drug delivery as the simplicity in fabrication, spontaneous enrichment on small molecules and biological macromolecules, and high drug loading capacity. Herein, in this study, a biocompatible diethylaminoethyl-dextran hydrochloride/sodium polyphenylene sulfonate coacervates, coated with eudragit S100 to improve the stability and colon targeting ability, named EU-Coac, is developed. Emodin, an active ingredient in traditional Chinese herbs proven to alleviate UC symptoms, is loaded in EU-Coac (EMO@EU-Coac) showing good stability in gastric acid and pepsin and pH-responsive release behavior. After oral administration, EMO@EU-Coac can effectively target and retain in the colon, displaying good therapeutic effects on UC treatment through attenuating inflammation and oxidative stress response, repairing colonic epithelia, as well as regulating intestinal flora balance. In short, this study provides a novel and facile coacervate microdroplet delivery system for UC treatment.

Hybrid biomineralized nanovesicles to enhance inflamed lung biodistribution and reduce side effect of glucocorticoid for ARDS therapy.

Acute respiratory distress syndrome (ARDS) is a critical illness characterized by severe lung inflammation. Improving the delivery efficiency and achieving the controlled release of anti-inflammatory drugs at the lung inflammatory site are major challenges in ARDS therapy. Taking advantage of the increased pulmonary vascular permeability and a slightly acidic-inflammatory microenvironment, pH-responsive mineralized nanoparticles based on dexamethasone sodium phosphate (DSP) and Ca2+ were constructed. By further biomimetic modification with M2 macrophage membranes, hybrid mineralized nanovesicles (MM@LCaP) were designed to possess immunomodulatory ability from the membranes and preserve the pH-sensitivity from core nanoparticles for responsive drug release under acidic inflammatory conditions. Compared with healthy mice, the lung/liver accumulation of MM@LCaP in inflammatory mice was increased by around 5.5 times at 48 h after intravenous injection. MM@LCaP promoted the polarization of anti-inflammatory macrophages, calmed inflammatory cytokines, and exhibited a comprehensive therapeutic outcome. Moreover, MM@LCaP improved the safety profile of glucocorticoids. Taken together, the hybrid mineralized nanovesicles-based drug delivery strategy may offer promising ideas for enhancing the efficacy and reducing the toxicity of clinical drugs.

Value of ultra-high b-value diffusion-weighted imaging for the evaluation of renal ischemia-reperfusion injury.

To explore the feasibility of ultra-high b-value diffusion-weighted imaging (ubDWI) in assessment of renal IRI. Thirty-five rabbits were randomized into a control group (n = 7) and a renal IRI group (n = 28). The rabbits in the renal IRI group underwent left renal artery clamping for 60 min. Rabbits underwent axial ubDWI before and at 1, 12, 24, and 48 h after IRI. Apparent diffusion coefficient (ADCst) were calculated from ubDWI with two b-values (b = 0, 1000 s/mm2). Triexponential fits were applied to calculate the pure diffusion coefficients (D), perfusion-related diffusion coefficient (D⁎), and ultra-high ADC (ADCuh). The interobserver reproducibility were evaluated. The repeated measurement analysis of variance and Spearman correlation analysis was used for statistical analysis. The ADCst, D, and ADCuh values showed good reproducibility. The ADCst, D, and D⁎ values of renal Cortex (CO) and outer medulla (OM) significantly decreased after IRI (all P < 0.05). The ADCuh values significantly increased from pre-IRI to 1 h after IRI (P < 0.05) and significantly declined at 24 h and 48 h after IRI (all P < 0.05). ADCuh was strongly positively correlated with AQP-1 in the renal CO and OM (ρ = 0.643, P < 0.001; ρ = 0.662, P < 0.001, respectively). ubDWI can be used to non-invasively evaluate early renal IRI, ADCuh may be adopted to reflect AQP-1 expression.