Targeting ENPP1 depletion may be a promising therapeutic strategy for treating oral squamous cell carcinoma via cytotoxic autophagy-related apoptosis.

ENPP1 depletion closely related with modulation immunotherapy of several types of cancer. However, the role of ENPP1 correlation with autophagy in oral squamous cell carcinoma (OSCC) pathogenesis remain unknown. In this study, effects of ENPP1 on OSCC cells in vitro were examined by cell proliferation assay, transwell chamber assay, flow cytometry analysis and shRNA technique. Cellular key proteins related to cell autophagy and apoptosis were evaluated by Western blot and immunofluorescent staining. Moreover, functions of ENPP1 on OSCC process were observed in nude mouse model. We reported that overexpression of ENPP1 promote the growth of OSCC cell xenografts in nude mouse model. In contrast, ENPP1 downregulation significantly inhibits OSCC cancer growth and induces apoptosis both in vitro and in vivo, which are preceded by cytotoxic autophagy. ENPP1downregulation induces a robust accumulation of autophagosomes, increases LC3B-II and decreases SQSTM1/p62 in ENPP1-shRNA-treated cells and xenografts. Mechanistic studies show that ENPP1 downregulation increases PRKAA1 phosphorylation leading to ULK1 activation. AMPK-inhibition abrogates ENPP1 downregulation-induced ULK1-activation, LC3B-turnover and SQSTM1/p62-degradation while AMPK-activation potentiates it's effects. Collectively, these data uncover that ENPP1 downregulation induces autophagic cell death in OSCC cancer, which may provide a potential therapeutic target for the treatment of OSCC.

miR-497-5p promoted neuronal injury in ischemic stroke by inhibiting the BDNF/TrkB/PI3K/Akt pathway.

The aim of this study was to investigate the molecular mechanism by which miR-497-5p regulates neuronal injury after ischemic stroke through the BDNF/TrkB/Akt signaling pathway. PC12 cells were used to construct a stroke injury model by oxygen-glucose deprivation/reoxygenation (OGD/R). The expression level of miR-497-5p was measured by RT-qPCR. CCK-8 kit was used to detect cell viability. Cell apoptosis and reactive oxygen species (ROS) were detected by flow cytometry. MDA and SOD detection kits were used to detect MDA content and SOD activity. A double luciferase reporter system was used to verify the targeting relationship between miR-497-5p and BDNF. The expression of BDNF, TrkB, p-TrkB, Akt and p-Akt was detected by Western blot. We have found that miR-497-5p expression was inhibited after treatment with OGD/R. Simultaneously, cell apoptosis, MDA content and ROS were upregulated, while cell viability and SOD were significantly decreased in PC12 cells. The effects of OGD/R on PC12 cells were reversed with the downregulation of miR-497-5p. A double luciferase reporter assay demonstrated that miR-497-5p negatively targets BDNF. BDNF inhibited cell apoptosis and oxidative stress injury in PC12 cells. These findings suggest that miR-497-5p aggravates neuronal injury in experimental model of ischemic stroke by inhibiting the BDNF/TrkB/PI3K/Akt signaling pathway.

The incidence and risk factors of unplanned removal of peripherally inserted central catheters among adult patients: A multi-centre cohort study.

AIMS AND OBJECTIVES: (i) To estimate the national incidence of unplanned removal of peripherally inserted central catheters (PICCs) in China. (ii) To explore the associated risk factors to provide evidence for the prevention. DESIGN: A multi-centre prospective cohort study. METHODS: A representative sample of 3222 Chinese adult patients with successful PICC insertion was recruited for the PICC Safety Management Research (PATH) using a two-stage cluster sampling method from December 2020 to June 2022. Sixty hospitals from seven Chinese provinces representing all geographical regions were selected. Demographic information and PICC characteristics were collected using a standard online case report form. Risk factors for the unplanned removal of PICCs were assessed using a cause-specific hazard model and verified using a sub-distribution hazard model. STROBE guidelines were followed in reporting this study. RESULTS: Three thousand one hundred and sixty-six patients were included in the final analysis with a mean age of 59 years and a total of 344,247 catheter days. The incidence of unplanned removal was 10.04%. Female, with thrombosis history, PICC insertion due to infusion failure, valved catheter and double-lumen catheter were risk factors, whereas longer insertion and exposure length were protective factors in the cause-specific hazard model. Higher BMI became an independent risk factor in the sub-distribution hazard model. CONCLUSIONS: Unplanned removal of PICCs is a serious clinical challenge in China. Our findings call for prevention strategies targeting the identified risk factors. RELEVANCE TO CLINICAL PRACTICE: Our study characterised the epidemiology of unplanned removal of PICCs among Chinese adult inpatients, highlighting the need for prevention among this population and providing a basis for the formulation of relevant prevention strategies. PATIENT OR PUBLIC CONTRIBUTION: Patients contributed through sharing their information required for the case report form. Healthcare professionals who provide direct care to the patient at each medical centre contributed by completing the online case report form.

A Comprehensive Ultrasound Investigation of Lower Facial and Neck Structure.

BACKGROUND: The jawline and neck significantly influence facial aesthetics. Botulinum toxin and filler are highly favored as minimally invasive jawline rejuvenation procedures. However, little evidence exists on the age-related skin and superficial fat tissue transformations in healthy individuals to guide targeted interventions. METHODS: A quantitative sonographic assessment was conducted on 51 patients. Total soft tissue thickness (the skin and superficial fat compartments) was measured at eight sites along the jawline and four sites at the neck. Among them, 21 patients received botulinum toxin A (BTX-A) injections for jawline lift. Three-dimensional images and questionaries were obtained before and after the treatment. RESULTS: In this ultrasound study, total superficial soft tissue thickness decreased significantly from the prejowl sulcus to the lateral cheek, with the jowl showing the greatest thickness. Vertically, significant differences in thickness were noted between superior and inferior points, especially at the inferior prejowl sulcus for the middle-aged and the jowl for the elderly group when comparing across age groups. Soft tissue thickness at the neck decreased from zones 1 to 3, consistent in all age groups. BMI and age positively correlated with soft tissue thickness at the jawline and neck. Regarding BTX-A injections, participants described a pain-free injection process, of which 85.7% reported substantial aesthetic improvement and sharpening of the submental-cervical angle. CONCLUSIONS: This study quantified age-related changes in superficial soft tissues at the jawline and neck regions with ultrasound imaging. With aging, soft tissue thickness alters with high region-specificity. Tailoring interventions to the specific alterations within each age group can achieve optimal results with enhanced safety. This study provided a quantitative analysis of skin and superficial fat compartment thicknesses for the young, middle-aged, and elderly groups. This study illustrated how skin and superficial fat compartments change with age in a regionally specific manner for both the jawline and neck regions. This study revealed a positive association between BMI and age with skin and superficial fat tissue thicknesses, especially in areas like the jowl, submental, and neck. This study provided guidance for a safe and effective botulinum toxin. A injection method focusing on the injection depths and regions to achieve optimal jawline rejuvenation outcomes and patient experience. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Faster Return to Daily Activities and Better Pain Control: A Prospective Study of Enhanced Recovery After Surgery Protocol in Breast Augmentation.

BACKGROUND: Enhanced recovery after surgery (ERAS) has been proven to decrease the amount of opioid use and reduce postoperative pain for a variety of surgeries, including breast reconstruction. However, data on ERAS in breast augmentation is lacking. OBJECTIVES: This study aims to investigate the effectiveness and safety of ERAS for breast augmentation. METHODS: A standardized ERAS protocol was established with full consideration of all aspects of perioperative care. Patients undergoing implant-based breast augmentation were prospectively recruited between December 2020 and January 2023, and assigned to either the ERAS or non-ERAS group randomly. The primary outcome was the activity of daily living after surgery. The secondary was postoperative pain and other outcomes included time to freely elevation, vomiting frequency, the use of analgesics, and complications. RESULTS: A total of 122 patients were included, with 70 in the ERAS group and 52 in the non-ERAS group. Compared to non-ERAS patients, ERAS patients had a shorter time to freely elevation of upper limbs (2.3 d vs. 5.5 d, P < 0.001). For ERAS patients, the pain scores were significantly lower on postoperative days 1 to 3, the activity of daily living index was significantly higher on postoperative days 1 to 3 and the opioids consumption was decreased (7.1 mg vs. 46.2 mg, P = 0.018). No difference was observed in complication and hospital costs between the two groups. CONCLUSION: The ERAS protocol significantly reduced postoperative pain and the use of opioids and promoted a return to daily activities without increasing complications in breast augmentation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Noncovalent Dual-Locked Near-Infrared Fluorescent Probe for Precise Imaging of Tumor via Hypoxia/Glutathione Activation.

Stimulus-responsive fluorescent probes have broad applications in the early detection and treatment of tumors and thus promote the personalized treatment of tumors and improve patient survival. Among the repertoires of probes, dual-locked near-infrared (NIR) fluorescent probes are of great significance due to their improved specificity and multiplex detection in tumor imaging but remain to be explored. In this work, a facile noncovalent strategy for constructing dual-locked probes was proposed. A glutathione (GSH)-activatable single-locked probe CySS (first lock) was preloaded into a hypoxia-responsive molecular container CF3C4A (second lock) through a host-guest interaction to form the dual-locked probe CF3C4A-CySS. Under physiological conditions, CF3C4A-CySS binds strongly to avoid undesired leakage in normal tissues. We have proven that CF3C4A-CySS can be activated and "turn on" its NIR fluorescent signal under the dual key stimulation of hypoxia and GSH in the tumor microenvironment, which enables precise tumor imaging with enhanced accuracy and specificity. Both in vitro and in vivo results indicated the superiority of CF3C4A-CySS in tumor imaging. This work not only provides an effective tool for tumor imaging but also proposes a promising strategy for dual-locked imaging agent construction.

Rapid and Selective 19F NMR-Based Sensors for Fingerprint Identification of Ribose.

Ribose plays an important role in the process of life. Excessive ribose in the human cerebrospinal fluid or urine can be used as an early diagnostic marker of leukoencephalopathy. Fluorinated phenylboronic acid combined with 19F NMR spectroscopy was a powerful method for molecular recognition. However, phenylboronic acid-based sensors for selective detection of ribose are rarely reported in the literature. In this study, the rapid and highly selective recognition of ribose was studied by 19F NMR and 2-fluorophenylboric acid. It was found that 2-fluoro-phenylboric acid was an appropriate 19F NMR-based sensor molecule for the determination of ribose under physiological conditions with high selectivity and robust anti-interference ability. When 2-fluorophenylboric acid was used for the detection of ribose in human urine without any sample pretreatment, a limit of detection of 78 µM was obtained at room temperature under given 19F NMR experimental conditions (400 MHz, 512 scans, ca. 12 min), which can well meet the needs of practical application.

Antibacterial activity and action mechanism of flavonoids against phytopathogenic bacteria.

As the most difficult to control in plant disease, phytopathogenic bacteria cause huge losses to agricultural products and economy worldwide. However, the commercially available bactericides are few and enhance pathogen resistance. To alleviate this situation, 50 flavonoids were evaluated for their antibacterial activities and mechanism of action against two intractable plant bacterial pathogens. The results of bioassays showed that most of the flavonoids exhibited moderate inhibitory effects against Xanthomonas oryzae (Xo) and Xanthomonas axonopodis pv citri (Xac). Remarkably, kaempferol showed excellent antibacterial activity against Xo in vitro (EC50 = 15.91 µg/mL) and quercetin showed the best antibacterial activity against Xac in vitro (EC50 = 14.83 µg/mL), which was better than thiodiazole copper (EC50 values against Xo and Xac were 16.79 µg/mL, 59.13 µg/mL, respectively). Subsequently, in vivo antibacterial activity assay further demonstrated kaempferol exhibited a stronger control effect on bacterial infections than thiodiazole copper. Then, the preliminary antibacterial mechanism of kaempferol was investigated by ultrastructural observations, transcriptomic, qRT-PCR analysis and biochemical index determination. These results showed that kaempferol mainly exerted bacteriostatic effects at the molecular level by affecting bacterial energy metabolism, reducing pathogenicity, and leading to disruption of cellular integrity, leakage of contents and cell death eventually.

Fluorometric assay based on the in situ formation of silicon nanoparticles for the determination of ß-glucuronidase.

As a prodrug-converting enzyme, ß-glucuronidase (ß-GCase) is a lysosomal enzyme participating in the release of glucose from glucopyranosyl glycoside. In this work, for the first time, we have developed an analytical method exhibiting fluorometric signals for straightforward determination of ß-GCase using silicon nanoparticles (Si NPs). Via hydrothermal treatment, in the water bath of 70 °C for 50 min, dopamine (DA) reacts with (3-[2-(2-aminoethylamino) ethylamino] propyltrimethoxysilane) (AEEA) to produce green fluorescent Si NPs. Enlightened by such easy reaction and ß-GCase-triggered specific hydrolysis of dopamine-4-ß-D-glucuronide (DA-GCU) into DA, we have designed an analytical method for ß-GCase sensing through the production of Si NPs. Therefore, through the designed sensing platform, ß-GCase activity was monitored, and the limit of detection (LOD) for this study was 0.02 U/L. Furthermore, the feasibility of the method was assessed by measuring ß-GCase activity in human serum where recoveries and RSD were in the ranges 99-104% and 1.37-3.44, respectively.

Three-dimensional tree-like branched TiO2 nanorods for the highly selective enrichment and determination of lead.

Branched titanium dioxide nanorods (B-TiO2 NRs) grown on fluorine-doped tin oxide glass (FTO) were developed, which can be used as a solid-phase extractant for preconcentration and determination of trace Pb(II) combined with inductively coupled plasma optical emission spectrometry (ICP-OES). The B-TiO2 NR-based glass substrate displayed excellent adsorptive selectivity and capacity for Pb(II); the maximum adsorption capacity was found to be 168.4 mg⋅g-1 PB(II) at pH = 5.0. It proved that the primary extraction mechanism was attributed to soft acid/soft base interactions to form complexes for chemisorption. Investigating the adsorption kinetics and isotherms indicated that the pseudo-second-order and Langmuir models can better describe Pb(II) adsorption on the B-TiO2 NRs. The proposed method presented good linearity from 0.01 to 5 mg⋅L-1 with a correlation coefficient (R2) of 0.9989 and a low limit of detection (LOD) of 2.2 µg⋅L-1 for Pb(II) under optimal conditions. The method was successfully applied to Pb(II) determination in foodstuffs with desirable recoveries from 93.18 to 108.1% and good precision with an RSD of less than 12.2%. This work provides a new strategy for selective extraction and determination of Pb(II) in complicated matrix samples.

Enhancing anoxic denitrification of low C/N ratio wastewater with novel ZVI composite carriers.

External organic carbon sources are needed to provide electron donors for the denitrification of wastewater with a low COD/NO3--N (C/N) ratio, increasing the treatment cost. The economic strategy is to enhance the bioactivity and/or biodiversity of denitrifiers to efficiently utilize organic substances in wastewater. In this study, novel zero-valent iron (ZVI) composite carriers were prepared and implemented in a suspended carrier biofilm reactor to enhance the bioactivity and/or biodiversity of denitrifiers. At the influent C/N ratio of 4 (COD was 179.5 ± 5.0 mg/L and TN was 44.2 ± 0.8 mg/L), COD and TN removal efficiencies were 85.1% and 66.4%, respectively, in the reactors filled with 3 wt% ZVI composite carriers. In contrast, COD and TN removal efficiencies were 70.4% and 55.3%, respectively, in the reactor filled with conventional high-density polyethylene (HDPE) biofilm carriers. The biofilm formation on the 3 wt% ZVI composite carriers was optimized due to its higher roughness (surface square roughness increased from 76.0 nm to 93.8 nm) and favorable hydrophilicity (water contact angle dropped to 72.5° ± 1.4° from 94.3° ± 3.2°) compared with the HDPE biofilm carriers. In addition, heterotrophic denitrifiers, Thauera and Dechloromonas, were enriched, whereas autotrophic denitrifiers, Raoultella and Thiobacillus, exhibited high relative abundance in the biofilm of ZVI composite carriers. The coexistence of heterotrophic denitrifiers and autotrophic denitrifiers on the surface of ZVI composite carriers provided mixotrophic metabolism of denitrification (including heterotrophic and iron-based autotrophic), thereby ensuring effective denitrification for wastewater with a low C/N ratio without external organic carbon source addition.

[Study on transport of small molecule rhodamine B within different layers of cartilage].

The small molecule nutrients and cell growth factors required for the normal metabolism of chondrocyte mainly transport into the cartilage through free diffusion. However, the specific mass transfer law in the cartilage remains to be studied. In this study, using small molecule rhodamine B as tracer, the mass transfer models of cartilage were built under different pathways including surface pathway, lateral pathway and composite pathway. Sections of cartilage at different mass transfer times were observed by using laser confocal microscopy and the transport law of small molecules within different layers of cartilage was studied. The results showed that rhodamine B diffused into the whole cartilage layer through surface pathway within 2 h. The fluorescence intensity in the whole cartilage layer increased with the increase of mass transfer time. Compared to mass transfer of 2 h, the mean fluorescence intensity in the superficial, middle, and deep layers of cartilage increased by 1.83, 1.95, and 3.64 times, respectively, after 24 h of mass transfer. Under lateral path condition, rhodamine B was transported along the cartilage width, and the molecular transport distance increased with increasing mass transfer time. It is noted that rhodamine B could be transported to 2 mm away from cartilage side after 24 h of mass transfer. The effect of mass transfer under the composite path was better than those under the surface path and the lateral path, and especially the mass transfer in the deep layer of cartilage was improved. This study may provide a reference for the treatment and repair of cartilage injury.

Noncovalent Theranostic Prodrug for Hypoxia-Activated Drug Delivery and Real-Time Tracking.

Real-time tracking of hypoxia-activated prodrugs (HAPs) delivery and the release process is of great significance for innovative medical treatments and drug development. Existing theranostic methods for HAPs activation imaging are based on the covalent approach, which suffered from complicated molecular design and tedious synthesis. In this work, a facile noncovalent strategy for constructing an hypoxia-activated theranostic prodrug has been proposed. An hypoxia-activated prodrug, NMAC4A, has been synthesized and bound with an NIR fluorophore CyNH2 through host-guest interaction to form the theranostic prodrug NMAC4A-CyNH2. Interestingly, the NIR fluorescence signal of CyNH2 can be effectively "turned off" after the formation of the stable theranostic prodrug NMAC4A-CyNH2. Because of the selective response to a tumor hypoxic microenvironment, NMAC4A-CyNH2 can realize the tumor-targeted drug delivery, accompanied by its NIR fluorescence "turn on". The synchronization of drug release and fluorescence "turn on" properties of NMAC4A-CyNH2 in an hypoxic microenvironment makes the fluorescence signal an effective tool for a precise tracing of the drug release process. Notably, NMAC4A-CyNH2 has been successfully applied to real-time image tracking of the drug delivery in vitro and in vivo. More importantly, the biodistribution of the theranostic prodrug's metabolites in a tumor and some major tissues have been mapped by mass spectrometry imaging at the molecular level, which further validated the effectiveness of NMAC4A-CyNH2 as a tumor-targeted drug delivery platform and NIR probe. This work will not only provide a promising tool for an hypoxia-activated drug delivery and real-time image tracking but also propose an effective design strategy for noncovalent theranostic prodrug construction.

A Bisboronic Acid Sensor for Ultra-High Selective Glucose Assay by 19F NMR Spectroscopy.

Glucose is a significant analyte both in biology and biomedical science, it is of great importance to selectively detect glucose both in body fluids and complex mixture. In this study, a simple 19F NMR based sensor was synthesized easily, which exhibited a high selectivity and robust anti-interference ability toward glucose detection both in a mixture containing up to 10 saccharides and human urine samples without any pretreatment. Combined with this sensor system, glucose could be well detected in human urine samples and the limit of detection was 0.41 mM by using a 400 MHz NMR spectrometer with 128 scans (ca. 4 min). This method had a potential for specific detection of glucose in complex mixture and diagnosis of diabetes mellitus related diseases in body fluid.

α-Glucosidase-Triggered Reaction for Fluorometric and Colorimetric Assays Based on the Formation of Silicon-Containing Nanoparticles.

Designing analytical approaches for enzymatic activity monitoring with high sensitivity and selectivity is of critical value for the diagnosis of diseases and biomedical studies. In this study, we have created a facile one-step synthetic route to prepare orange-red color and yellow fluorescent silicon-containing nanoparticles (Si CNPs) by mixing 3(2-aminoethylamino) propyl (dimethoxymethylsilane) and hydroquinone (HQ) in an aqueous solution. Inspired by the HQ-regulated facile synthetic step and the generation of HQ from α-glucosidase (α-Glu)-catalyzed hydrolysis of 4-hydroxyphenyl-α-d-glucopyranosyl (4-HPαDG), we have designed a straightforward colorimetric and fluorometric α-Glu activity assay using a commercially available 4-HPαDG as the α-Glu substrate. Fluorescent and colorimetric assays for α-Glu activity measurement have been thereby established and exhibited detection limits as low as 0.0032 and 0.0046 U/mL, respectively. Under single excitation at 370 nm, the prepared Si CNPs emitted yellow fluorescence at 520 nm and exhibited an absorbance peak at 390 nm. In addition, the proposed approach reveals various advantages including easy operation, time-saving, and good anti-interference ability. Hence, it could improve the progress of fluorometric and colorimetric enzymatic activity assays with high sensitivity and simplicity. Moreover, the proposed approach was applied for α-Glu inhibitor screening, and its feasibility in real samples was measured by detecting the α-Glu activity in human serum samples.

Narjatamolide, an Unusual Homoguaiane Sesquiterpene Lactone from Nardostachys jatamansi.

Narjatamolide (1), an unusual homoguaiane sesquiterpene lactone, was isolated from the roots and rhizomes of Nardostachys jatamansi DC. It represents the new carbon skeleton of a homoguaiane sesquiterpenoid possessing an additional acetate unit spiro-fused with C-4 and C-15 to form a cyclopropane ring. The structure of 1 was elucidated by extensive spectroscopic analyses, and the absolute configuration was confirmed by the electronic circular dichroism (ECD) calculations and X-ray single-crystal diffraction analysis. Compound 1 showed antiproliferative effects against BEL-7402 cell lines with an IC50 value of 5.67 ± 1.43 µM, and the mechanism study showed that 1 induces cell cycle of BEL-7402 cell lines arrest at G2/M phase.

Fluorescence "turn-on" of silicon-containing nanoparticles for the determination of resorcinol.

A fluorescent nanosensor based on silicon-containing nanoparticles (Si CNPs) with green fluorescence (FL) was prepared by one-step method. The prepared Si CNPs emitted green FL at 470 nm under the excitation at 350 nm. The FL signal of Si CNPs reveals an obvious enhancement in the presence of resorcinol (RC), due to the passivation of surface trap states of Si CNPs via the binding of OH group of RC with the NH group of Si CNPs, which allowed the formation of new radiative electron-hole recombination centers. This was confirmed by some analytical experiments performed on zeta potential, FL lifetime steady state, and the FTIR spectra. Most importantly, this nanosensor could selectively determine RC with high sensitivity and without interference from hydroquinone (HQ) and catechol (CT) as RC isomers. RC was detected in the linear range 0.05-40 µM, with a detection limit of 0.012 µM. The synthesized nanosensor was applied to the determination of RC in fresh fruit juice and water samples. The collected results confirmed the feasibility of our approach with high accuracy.

Fungicidal Activity and Mechanism of Action of Glabridin from Glycyrrhiza glabra L.

Glycyrrhiza glabra (Licorice) belongs to the Fabaceae family and its extracts have exhibited significant fungicidal activity against phytopathogenic fungi, which has mainly been attributed to the presence of phenolic compounds such as flavonoids, isoflavonoids and chalcones. In this study, a series of licorice flavonoids, isoflavonoids and chalcones were evaluated for their fungicidal activity against phytopathogenic fungi. Among them, glabridin exhibited significant fungicidal activity against ten kinds of phytopathogenic fungi. Notably, glabridin displayed the most active against Sclerotinia sclerotiorum with an EC50 value of 6.78 µg/mL and was 8-fold more potent than azoxystrobin (EC50, 57.39 µg/mL). Moreover, the in vivo bioassay also demonstrated that glabridin could effectively control S. sclerotiorum. The mechanism studies revealed that glabridin could induce reactive oxygen species accumulation, the loss of mitochondrial membrane potential and cell membrane destruction through effecting the expression levels of phosphatidylserine decarboxylase that exerted its fungicidal activity. These findings indicated that glabridin exhibited pronounced fungicidal activities against S. sclerotiorum and could be served as a potential fungicidal candidate.

[Current Progress on Biological Evaluation for Medical Devices].

To broadly understand the new direction of biological evaluation for medical devices, we introduced both domestic and international progress of biological evaluation and focused on illustrating the key points on full life-cycle biological evaluation, toxicological risk evaluation, evaluation endpoints and package material evaluation concern as well as how to use the update vision of ISO 10993-1:2018 scientifically and reasonably in order to provide us better services on performing biological evaluation for medical devices.

Precisely Traceable Drug Delivery of Azoreductase-Responsive Prodrug for Colon Targeting via Multimodal Imaging.

We report the development of an azoreductase-responsive prodrug AP-N═N-Cy in which the precursor compound AP, a readily available podophyllotoxin derivative, is linked with a NIR fluorophore (Cy) via a multifunctional azobenzene group. This type of azo-based prodrug can serve as not only an azoreductase-responsive NIR probe to real-time tracking of the drug delivery process but also a delivery platform for an anticancer compound (AdP). We have shown that cleavage of the multifunctional azobenzene group in AP-N═N-Cy only occurred in the presence of azoreductase, which specifically secretes in the colon, resulting in direct release of AdP through an in situ modification of a phenylamino group on the precursor AP. Moreover, introduction of the azobenzene group endows the prodrug with an unique fluorescence "off-on" property and served as a switch to "turn on" the fluorescence of Cy as consequence of a self-elimination reaction with breakage of an azo bond. Such a prodrug can be administered orally and exhibit high stability and low toxicity before arriving at the colon. In view of the synchronism of drug release and the fluorescence turn-on process, the fluorescence imaging method was utilized to precisely trace drug delivery in vitro, ex vivo, and in vivo. Distinguishingly, the biodistribution of AdP and Cy in various tissues was further precisely mapped at the molecular level using imaging mass spectrometry. To the best of our knowledge, this is the first time that the in vivo real-time precise tracking of the colon-specific drug release and biodistribution was reported via a multimodal imaging method.