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Organelles are responsible for the efficient storage and transport of substances in living systems. A myriad of extracellular vesicles (EVs) acts as a bridge to exchange signaling molecules in cell–cell communication, and the highly dynamic tubulins and actins contribute to efficient intracellular substance transport. The inexhaustible cues of natural cargo delivery by organelles inspire researchers to explore the construction of biomimetic architectures for “smart” delivery carriers. Herein, we report a 10-hydroxycamptothecin (HCPT)-peptide conjugate HpYss that simulates the artificial EV-to-filament transformation process for precise liver cancer therapy. Under the sequential stimulus of extracellular alkaline phosphatase (ALP) and intracellular glutathione (GSH), HpYss proceeds via tandem self-assembly with a morphological transformation from nanoparticles to nanofibers. The experimental phase diagram elucidates the influence of ALP and GSH contents on the self-assembled nanostructures. In addition, the dynamic transformation of organelle-mimetic architectures that are formed by HpYss in HepG2 cells enables the efficient delivery of the anticancer drug HCPT to the nucleus, and the size–shape change from extracellular nanoparticles (50–100 nm) to intracellular nanofibers (4–9 nm) is verified to be of key importance for nuclear delivery. Nuclear targeting of HpYss amplifies apoptosis, thus significantly enhancing the inhibitory effect of HCPT (>10-fold) to HepG2 cells. Benefitting from the spatiotemporally controlled nanostructures, HpYss exhibited deep penetration, enhanced accumulation, and long-term retention in multicellular spheroid and xenograft models, potently abolishing liver tumor growth and preventing lung metastasis. We envision that our organelle-mimicking delivery strategy provides a novel paradigm for designing nanomedicine to cancer therapy., Graphical abstract Image 1, Highlights • An organelle-inspired nanomedicine for precise liver cancer therapy is proposed. • The delivery process mimics the transport of extracellular vesicles and filaments. • The extra- and intracellular tandem self-assembly influence the nanostructures. • The dynamic size–shape change of nanomedicine actuates the nuclear delivery. • Spatiotemporally controlled nanomedicine abolishes liver tumor growth and lung metastasis.

An abnormal level of SO2 is closely related to many diseases. Therefore, developing an effective method for the detection of SO2 in biological environments has important physiological and pathological significance. In this work, a new fluorescent probe (CA-SO2) was designed and synthesized for efficiently and specifically detecting SO2 derivatives through nucleophilic addition reaction. The novel fluorescent probe (CA-SO2) showed high selectivity, fast response time (within 50 s), and low detection limit (LOD = 75 nM). Furthermore, after adding SO2 derivatives to the probe solution, the color of the solution changes from orange to colorless, which allows “naked eye” detection for SO2. Moreover, the probe has a large Stokes shift (129 nm) and excellent biocompatibility. The probe has been successfully applied to the detection of SO2 derivatives in living cells and zebrafish.

X-ray computed tomography (CT), as one of the most widely used noninvasive imaging modalities, can provide three-dimensional anatomic details with high resolution, which plays a key role in disease diagnosis and treatment assessment. However, although they are the most prevalent and FDA-approved contrast agents, iodinated water-soluble molecules still face some challenges in clinical applications, such as fast clearance, serious adverse effects, nonspecific distribution, and low sensitivity. Because of their high biocompatibility, tunable designability, controllable biodegradation, facile synthesis, and modification capability, the polymers have demonstrated great potential for efficient delivery of iodinated contrast agents (ICAs). Herein, we comprehensively summarized the applications of multifunctional polymeric materials for ICA delivery in terms of increasing circulation time, decreasing nephrotoxicity, and improving the specificity and sensitivity of ICAs for CT imaging. We mainly focused on various iodinated polymers from the aspects of preparation, functionalization, and application in medical diagnosis. Future perspectives for achieving better imaging and clinical translation are also discussed to motivate new technologies and solutions.

Background:Nuezhenide (NZD), an iridoid glycoside isolated from Ilex pubescens Hook. & Arn. var. kwangsiensis Hand.-Mazz., used as a traditional Chinese medicine for clearing Hook. & Arn. var. kwangsiensis Hand.-Mazz., used as a traditional Chinese medicine for clearing away heat and toxic materials, displays a variety of biological activities such as anti-tumor, antioxidant, and other life-protecting activities. However, a few studies involving anti-inflammatory activity and the mechanism of NZD have also been reported. In the present study, the anti-inflammatory and antioxidative effects of NZD are illustrated.Objective:This study aims to test the hypothesis that NZD suppresses LPS-induced inflammation by targeting the NF-κB pathway in RAW264.7 cells.Methods:LPS-stimulated RAW264.7 cells were employed to detect the effect of NZD on the release of cytokines by ELISA. Protein expression levels of related molecular markers were quantitated by western blot analysis. The levels of ROS, NO, and Ca2+were detected by flow cytometry. The changes in mitochondrial reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were observed and verified by fluorescence microscopy. Using immunofluorescence assay, the translocation of NF-κB/p65 from the cytoplasm into the nucleus was determined by confocal microscopy.Results:NZD exhibited anti-inflammatory activity and reduced the release of inflammatory cytokines such as nitrite, TNF-α, and IL-6. NZD suppressed the expression of the phosphorylated proteins like IKKα/β, IκBα, and p65. Besides, the flow cytometry results indicated that NZD inhibited the levels of ROS, NO, and Ca2+in LPS-stimulated RAW264.7 cells. JC-1 assay data showed that NZD reversed LPS-induced MMP loss. Furthermore, NZD suppressed LPS-induced NF-B/p65 translocation from the cytoplasm into the nucleus.Conclusions:NZD exhibits anti-inflammatory effects through the NF-κB pathway on RAW264.7 cells.

Systemic acquired resistance (SAR) is induced by pathogens and confers protection against a broad range of pathogens. Several SAR signals have been characterized, but the nature of the other unknown signalling by small metabolites in SAR remains unclear. Glutathione (GSH) has long been implicated in the defence reaction against biotic stress. However, the mechanism that GSH increases plant tolerance against virus infection is not entirely known. Here, a combination of a chemical, virus‐induced gene‐silencing‐based genetics approach, and transgenic technology was undertaken to investigate the role of GSH in plant viral resistance in Nicotiana benthamiana. Tobacco mosaic virus (TMV) infection results in increasing the expression of GSH biosynthesis genes NbECS and NbGS, and GSH content. Silencing of NbECS or NbGS accelerated oxidative damage, increased accumulation of reactive oxygen species (ROS), compromised plant resistance to TMV, and suppressed the salicylic acid (SA)‐mediated signalling pathway. Application of GSH or l‐2‐oxothiazolidine‐4‐carboxylic acid (a GSH activator) alleviated oxidative damage, decreased accumulation of ROS, elevated plant local and systemic resistance, enhanced the SA‐mediated signalling pathway, and increased the expression of ROS scavenging‐related genes. However, treatment with buthionine sulfoximine (a GSH inhibitor) accelerated oxidative damage, elevated ROS accumulation, compromised plant systemic resistance, suppressed the SA‐mediated signalling pathway, and reduced the expression of ROS‐regulating genes. Overexpression of NbECS reduced oxidative damage, decreased accumulation of ROS, increased resistance to TMV, activated the SA‐mediated signalling pathway, and increased the expression of the ROS scavenging‐related genes. We present molecular evidence suggesting GSH is essential for both local and systemic resistance of N. benthamiana to TMV through a differential modulation of SA and ROS., Glutathione is required for both local and systemic resistance of Nicotiana benthamiana to tobacco mosaic virus infection through a differential modulation of salicylic acid signalling and reactive oxygen species.

Two mononuclear Pt(II) compounds, [Pt(BQL1)Cl]Cl (BQL1-Pt) and [Pt(BQL2)Cl]Cl (BQL2-Pt), with [5-(benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-pentyl]-bis-pyridin-2-ylmethyl-amine (BQL1) and [9-(benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-nonyl]-bis-pyridin-2-ylmethyl-amine (BQL2), were prepared as new chemotypes for potential antitumor agents. In this study, the effects of cryptolepine derivatives in BQL1-Pt, 2,2′-dipicolylamine Pt(II) complex, and BQL2-Pt on cellular Pt(II) accumulation, cytotoxicity, and in vitro and in vivo antitumor activities against T-24 cancer cells and normal HL-7702 cells were evaluated. BQL1-Pt and BQL2-Pt displayed cytotoxic activities in the micromolar range (1.3 ± 0.1 and 0.2 ± 0.2 μM, respectively) on T-24 cancer cells; however, they did not exhibit any toxicity against HL-7702 cells. They triggered T-24 cell apoptosis through a mitochondrial dysfunction pathway. BQL1-Pt and BQL2-Pt prepared from the neutral BQL1 and BQL2 ligands with cryptolepine derivatives showed better antitumor activities than 2,2′-dipicolylamine. Furthermore, BQL2-Pt effectively inhibited the growth of bladder T-24 tumor in vivo. BQL2-Pt could be a potential therapeutic candidate for cancers.

Acute lung injury (ALI) is a serious clinical disease. Rotundic acid (RA), a natural ingredient isolated from Ilex rotunda Thunb, exhibits multiple pharmacological activities. However, RA's therapeutic effect and mechanism on ALI remain to be elucidated. The present study aimed to further clarify its regulating effects on inflammation in vitro and in vivo. Our results indicated that RA significantly inhibited the overproduction of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). RA decreased ROS production and calcium influx. In addition, RA inhibited the activation of PI3K, MAPK, and NF-κB pathways and enhanced the activity of nuclear factor E2-related factor 2 (Nrf2) signaling. The cellular thermal shift assay and docking results indicated that RA bind to TLR4 to block TLR4 dimerization. Furthermore, RA pretreatment effectively inhibited ear edema induced by xylene and LPS-induced endotoxin death and had a protective effect on LPS-induced ALI. Our findings collectively indicated that RA has anti-inflammatory effects, which may serve as a potential therapeutic option for pulmonary inflammation.

A one-step protocol of the aryl iodine-catalyzed aminolactonization of unactivated alkenes under oxidation conditions was first reported to efficiently construct diverse amino lactones in a short time using HNTs2 as the compatible nitrogen source. In addition, we investigated the influence of the reaction rate based on the structure of the iodoarene precatalyst, which revealed the selective adjustment effect on aminolactonization and oxylactonization. Finally, preliminary experiments verified the feasibility of asymmetric aminolactonization catalyzed by a chiral iodoarene precatalyst.

It is challenging to construct high-performing excimer-based luminescent analytic tools at low molecular concentrations. We report that enzyme-instructed self-assembly (EISA) enables the monomer-excimer transition of a coumarin dye (Cou) at low molecular concentrations, and the resulting higher ordered luminescent supramolecular assemblies (i.e., nanofibers) efficiently record the spatiotemporal details of alkaline phosphatase (ALP) activity in vitro and in vivo. Cou was conjugated to short self-assembly peptides with a hydrophilic ALP-responsive group. By ALP triggering, EISA actuated a nanoparticles-nanofibers transition at low peptide concentrations followed by monomer-excimer transition of Cou. Analysis of structure-property relationships revealed that the self-assembly motif was a prerequisite for peptides to induce the monomer-excimer transition of Cou. Luminescent supramolecular nanofibers of pYD (LSN-pYD) illuminated the intercellular bridge of cancer cells and distinguished cancer cells (tissues) from normal cells (tissues) efficiently and rapidly, promising potential use for the early diagnosis of cancer. This work extends the functions of EISA and provides a new application of supramolecular chemistry.

GTPBP3 and MTO1 cooperatively catalyze 5-taurinomethyluridine (τm5U) biosynthesis at the 34th wobble position of mitochondrial tRNAs. Mutations in tRNAs, GTPBP3 or MTO1, causing τm5U hypomodification, lead to various diseases. However, efficient in vitro reconstitution and mechanistic study of τm5U modification have been challenging, in part due to the lack of pure and active enzymes. A previous study reported that purified human GTPBP3 (hGTPBP3) is inactive in GTP hydrolysis. Here, we identified the mature form of hGTPBP3 and showed that hGTPBP3 is an active GTPase in vitro that is critical for tRNA modification in vivo. Unexpectedly, the isolated G domain and a mutant with the N-terminal domain truncated catalyzed GTP hydrolysis to only a limited extent, exhibiting high Km values compared with that of the mature enzyme. We further described several important pathogenic mutations of hGTPBP3, associated with alterations in hGTPBP3 localization, structure and/or function in vitro and in vivo. Moreover, we discovered a novel cytoplasm-localized isoform of hGTPBP3, indicating an unknown potential noncanonical function of hGTPBP3. Together, our findings established, for the first time, the GTP hydrolysis mechanism of hGTPBP3 and laid a solid foundation for clarifying the τm5U modification mechanism and etiology of τm5U deficiency-related diseases.

Isoflurane (ISO) elicits protective effects on ischemia-induced brain injury. We investigated whether sub-anesthetic (0.7%) ISO post-conditioning attenuates the inflammation and apoptosis in oxygen-glucose deprivation (OGD)-insulted co-cultures (microglia and neurons) in vitro and the brain injury of the middle cerebral arterial occlusion (MCAO) rat. We demonstrated that ISO augmented the viability of OGD-treated microglia and neurons. ISO reduced the expression and activation of COX2 and iNOS in OGD-challenged microglia. ISO repressed the production of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, and monocyte chemoattractant protein-1 in OGD-exposed microglia. ISO also decreased nucleosomal fragmentation and caspase-3 activity but increased mitochondrial membrane potential in OGD-stimulated microglia and neurons. Mechanistically, ISO suppressed OGD-induced microglial inflammation by blocking ROS-regulated p38 MAPK/NF-κB signaling pathway and hampered OGD-triggered microglial apoptosis in a ROS- or NO-dependent fashion. In vivo results with MCAO rats were partly consistent with the in vitro observation. These findings indicate that sub-anesthetic ISO post-conditioning abates the inflammation and apoptosis in OGD-stimulated rat microglia and the apoptosis of OGD-exposed neurons and the brain injuries of MCAO rats, suggesting it as a potentially effective therapeutic approach for ischemic brain damages.

Metal–organic frameworks (MOFs), which have attracted widespread interest, are used for electrode materials in renewable clean energy production and storage because of the large surface area, high ...

A composite particle electrode Sn/Sb-Mn-GAC was prepared by impregnation with granular activated carbon (GAC) as carrier. The surface morphology, phase composition and electrochemical properties of the particle electrode were characterized by scanning electron microscopy, X-ray diffraction and electrochemical workstation. The results show that the Sn/Sb-Mn-GAC particles have uniform grain size, good dispersity and high oxygen evolution potential. The Sn/Sb-Mn-GAC particle electrode was used to the electrochemical degradation of 4-chlorophenol. It was shown that 4-chlorophenol was almost completely removed after electrolyzing for 60 min. A large number of intermediates were produced during the degradation of 4-chlorophenol in the experimental system. The main intermediate products were benzoquinone, 4-chlorocatechol, hydroquinone, fumaric acid, oxalic acid, etc., eventually mineralized into water and carbon dioxide. The degradation pathway of 4-chlorophenol were preliminarily suggested through the analysis of intermediates in degradation process. The supported Sn/Sb-Mn-GAC particle electrode can be repeated used 4 times in three-dimensional electrochemical reactor and the kinetic model for the electrochemical oxidation of 4-chlorophenol was established. The experimental results show that the degradation process of 4-chlorophenol accords with the first-order kinetic model, the correlation coefficient is 0.98 or more. The kinetic rate constant k of Sn/Sb-Mn-GAC particle electrode is reduced when it is repeated used, but the treatment efficiency of 4-chlorophenol is still better. The results of research show that the three-dimensional electrochemical reactor using Sn/Sb-Mn-GAC particle electrode has promising application prospects in the treatment of phenolic wastewater.

Purpose Two-dimensional creatine CEST (2D-CrCEST), with a slice thickness of 10-20 mm and temporal resolution (τRes ) of about 30 seconds, has previously been shown to capture the creatine-recovery kinetics in healthy controls and in patients with abnormal creatine-kinase kinetics following the mild plantar flexion exercise. Since the distribution of disease burden may vary across the muscle length for many musculoskeletal disorders, there is a need to increase coverage in the slice-encoding direction. Here, we demonstrate the feasibility of 3D-CrCEST with τRes of about 30 seconds, and propose an improved voxel-wise B 1 + -calibration approach for CrCEST. Methods The current 7T study with enrollment of 5 volunteers involved collecting the baseline CrCEST imaging for the first 2 minutes, followed by 2 minutes of plantar flexion exercise and then 8 minutes of postexercise CrCEST imaging, to detect the temporal evolution of creatine concentration following exercise. Results Very good repeatability of 3D-CrCEST findings for activated muscle groups on an intraday and interday basis was established, with coefficient of variance of creatine recovery constants (τCr ) being 7%-15.7%, 7.5%, and 5.8% for lateral gastrocnemius, medial gastrocnemius, and peroneus longus, respectively. We also established a good intraday and interday scan repeatability for 3D-CrCEST and also showed good correspondence between τCr measurements using 2D-CrCEST and 3D-CrCEST acquisitions. Conclusion In this study, we demonstrated for the first time the feasibility and the repeatability of the 3D-CrCEST method in calf muscle with improved B 1 + correction to measure creatine-recovery kinetics within a large 3D volume of calf muscle.

After an intravenous bolus injection of 100 mL of iodinated contrast agent (370 mgI/mL), the amount of iodine atoms entering the blood is tens of thousands of times the daily dose of iodine recommended by the World Health Organization. However, the effect of iodinated contrast in patients with nonthyroidal illness, manifested as reduced serum total triiodothyronine (TT3) concentrations, is unclear. We studied the effect of iodinated contrast on thyroid function and auto-antibodies in patients with reduced TT3 after diagnosis and treatment of coronary heart disease.This was a prospective cohort study. One hundred and fifty-four stable angina pectoris patients with reduced TT3 and normal thyroid-stimulating hormone (TSH), free thyroxine (FT4), and reverse triiodothyronine (rT3) were enrolled from January, 2017, to June, 2018. All subjects had no history of thyroid dysfunction and had no recent infections, tumors, trauma, or other critical illnesses. Fourty-one patients underwent coronary angiography and 113 patients underwent coronary intervention.There were 6 patients (3.9%) with hypothyroidism and 30 patients (19.5%) developed subclinical hypothyroidism (SCHypo) on the first day after surgery. There were 6 patients (3.9%) with hypothyroidism, 6 patients (3.9%) with SCHypo, and 18 patients (11.7%) with subclinical hyperthyroidism (SCHyper) at the first month postsurgery. There were 23 patients (14.9%) with SCHyper and 6 patients (3.9%) with SCHypo at the sixth month after surgery. No patient with longterm severe thyroid dysfunction occurred during follow-up. The levels of free triiodothyronine, FT4, TT3, total thyroxine, and TSH showed statistically significant changes at 1 day, and 1, 3, and 6 months postoperative (P.005). The level of rT3 showed no statistically significant change at 1, 3, and 6 months postoperative (P.05). The levels of thyroglobulin antibody and thyroid peroxidase antibody decreased at 6 months postoperative (P.001).The risk of subclinical thyroid dysfunction and transient hypothyroidism occurred with a single large dose of iodinated contrast in the diagnosis and treatment of coronary heart disease, but no longterm severe thyroid dysfunction occurred. Patients with preoperative thyroid antibody elevation were more likely to have subclinical thyroid dysfunction after surgery.FT3 = free triiodothyronine; FT4 = free thyroxine; PCI = percutaneous coronary intervention; rT3 = reverse triiodothyronine; SCHyper = subclinical hyperthyroidism; SCHypo = subclinical hypothyroidism; TGAB = thyroglobulin antibody; TPOAB = thyroid peroxidase antibody; TT3 = total triiodothyronine; TT4 = total thyroxine; TSH = thyroid-stimulating hormone; WHO = World Health Organization.

Lung cancer is the leading cause of cancer death and the most common malignant tumor, the long-term survival of which has stagnated in the past several decades. Pileostegia tomentella Hand. Mazz is a traditional Chinese medicine called "Zhongliuteng" (ZLT) in the pharmacopeia, which has been proved to possess a potent anti-tumor effect on various cancers. In this study, the effects of ZLT N-butanol extraction (ZLTN) and ZLT ethyl acetate extraction (ZLTE) on the viability of non-small cell lung cancer cell (NSCLC) lines H1299 and A549 were evaluated. Here, we firstly reported that ZLTE significantly inhibited H1299 cells growth without affecting the release of lactate dehydrogenase (LDH). In addition, ZLTE induced caspase-dependent apoptosis in a concentration-dependent manner and increased the expression cleaved-PARP and decreased pro-caspase-3, pro-caspase-7, pro-caspase-8, and pro-caspase-9. Moreover, ZLTE increased the level of cellular reactive oxygen species (ROS) in H1299 cells to lead to apoptosis, which was reversed by N-acetyl-cysteine (NAC). Taken together, our results revealed that ZLTE induced caspase-dependent apoptosis via ROS generation, suggesting that ZLTE is a promising herbal medicine for the treatment of NSCLC.

A waste cotton fabric (WCF)/zinc borate (ZB) composite aerogel with flame resistance was successfully synthesized through zinc borate immobilized in the cellulose aerogel by in situ formation by di...

BACKGROUND: Diffusion MRI is routinely used to evaluate brain injury in neonatal encephalopathy. Though abnormal mean diffusivity (MD) is often attributed to cytotoxic edema, the specific contribution from neuronal pathology is unclear. PURPOSE: To determine whether MD from high-resolution diffusion tensor imaging (DTI) can detect variable degrees of neuronal degeneration and pathology in piglets with brain injury induced by excitotoxicity or global hypoxia-ischemia (HI) with or without overt infarction. STUDY TYPE: Prospective. ANIMAL MODEL: Excitotoxic brain injury was induced in 6 neonatal piglets by intrastriatal stereotaxic injection of the glutamate receptor agonist quinolinic acid (QA). Three piglets underwent global HI or sham procedure. Piglets recovered for 20–96 hours before undergoing MRI (n=9). FIELD STRENGTH/SEQUENCE: 3.0T MRI with DTI, T(1)- and T(2)-weighted imaging. ASSESSMENT: MD, fractional anisotropy (FA), and qualitative T(2) injury were measured in putamen and caudate. The cell bodies of normal neurons, degenerating neurons (excitotoxic necrosis, ischemic necrosis, or necrosis-apoptosis cell death continuum), and injured neurons with equivocal degeneration were counted by histopathology. STATISTICAL TESTS: Spearman correlations were used to compare MD and FA to normal, degenerating, and injured neurons. T(2) injury and neuron counts were evaluated by descriptive analysis. RESULTS: The QA insult generated titratable levels of neuronal pathology. In QA, HI, and sham piglets, lower MD correlated with higher ratios of degenerating-to-total neurons (p0.99). Neuron counts were not related to FA (p>0.30) or to qualitative injury from T(2)-weighted MRI. DATA CONCLUSION: MD is more accurate than FA for detecting neuronal degeneration and loss during acute recovery from neonatal excitotoxic and HI brain injury. MD does not reliably detect non-fulminant, nascent, and potentially reversible neuronal injury.

The mRNA precursor 3′-end modification factor NUDT21 is a major regulator of 3′UTR shortening and an important component of pre-mRNA cleavage and polyadenylation. However, its role in pathologic progress of small cell lung cancer (SCLC) remains unclear. In this study, we observed that NUDT21 expression is downregulated in SCLC tissues. Hypoxia-induced down-regulation of NUDT21 through HIF-1α. NUDT21 shRNA transduction promotes proliferation and inhibits apoptosis of A549 cells. NUDT21 inhibition also promotes tumor growth in a mouse xenograft model. Furthermore, we clarified that HIF-1α mediated NUDT21 downregulation which altered the expression patterns of two isoforms of GLS1, GAC and KGA. These results link the hypoxic tumor environments to aberrant glutamine metabolism which is important for cellular energy in SCLC cells. Therefore, NUDT21 could be considered as a potential target for the treatment of SCLC.

Nitrogen (N) is the essential nutrient for wheat growth and development, its accumulation and metabolism controlled by many other elements. Zinc (Zn) is one of the important elements which tends to have effects on plant N homeostasis. Here in our study, 0 μM and 5 μM Zn was applied to the wheat seedlings culturing in 5 mM (+N) and 0.5 mM (-N) N treatments, respectively. The results showed that the shoot and root length growth performance, total N, NO3−, and amino acid concentrations, glutamine synthetase (GS) activity of wheat were facilitated by 5 μM Zn application under + N and –N conditions. Quantitative real-time PCR (qRT-PCR) analysis indicated that several NO3− transporters genes (TaNRT2.1, TaNPF7.1 and TaNPF7.2) and the genes encoding GS (TaGS1 and TaGS2) were induced by 5 μM Zn. In addition, transcriptional changes in wheat shoots and roots with Zn application were tested by RNA-seq techniques. A total of 147/551 induced and 36/2162 reduced differentially expression genes (DEGs) was detected in wheat shoots/roots, respectively. GO and KEGG enrichment analyses showed that 5 μM Zn mainly affected the glutathione (GSH) metabolism, phenylpropanoid biosynthesis and amino acid metabolism, involving in N homeostasis. Furthermore, the relative expression of genes related to phenylalanine, cysteine and methionine metabolism was induced by 5 μM Zn to promote the amino acid accumulation. Overall, these results highlight the facilitating of N accumulation by low level Zn, and provide an insight into the effects of Zn on N metabolism in wheat.

This article has been retracted, and the online PDF has been watermarked “RETRACTION”. The retraction notice is available at http://doi.org/10.3233/MGC-220954.

At present, several reports have indicated that the C-terminal peptides of tissue factor pathway inhibitor 1 (TFPI-1) were active antibacterial peptides. However, the functions of TFPI-1 C-terminal peptides in teleost are still very limited. In this study, a C-terminal peptide, TC26 (with 26 amino acids), derived from common carp (Cyprinus carpio) TFPI-1, was synthesized and investigated for its antibacterial spectrum, action mechanism, as well as the in vivo effects on bacterial invasion. Our results showed that TC26 was active against Gram-positive bacteria Micrococcus luteus and Staphylococcus aureus, as well as Gram-negative bacterium Vibrio vulnificus. TC26 treatment facilitated the bactericidal process of erythromycin by enhancing the out-membrane permeability of V. vulnificus. During the bactericidal process, TC26 killed the target bacterial cells Vibrio vulnificus, by destroying cell membrane integrity, penetrating into the cytoplasm and inducing degradation of genomic DNA and total RNA. In vivo study showed that administration of turbot with TC26 before bacterial infection significantly reduced pathogen dissemination and replication in tissues. These results indicated that TC26 is a novel and active antibacterial peptide and may play a vital role in fighting pathogenic infection in aquaculture.

Solubility of 1-butyl-3-methylimidazolium bis[(trifluoromethyl)sulfanilamide] ([Bmim][NTf2]) and 1-butyl-3-methylimidazolium acetate ([Bmim][Ac]) in supercritical carbon dioxide (scCO2) using ethan...

To increase the oxygen concentration in the product gas of a chemical looping air separation (CLAS) system, it is important to reduce the oxygen uncoupling temperature of the oxygen carrier (OC). In this paper, it is investigated whether and to what extent the addition of Mn2O3, Co3O4, Pb3O4, and Cr2O3, all of which have oxygen uncoupling propensity according to thermodynamics, to CuO improves the oxygen uncoupling behavior of the mixed-oxide OC at lower temperatures. Using thermogravimetric analyses, it is shown that the oxygen uncoupling temperature of a Cu-Mn composite OC is decreased by approximately 200 °C relative to a Cu OC. In addition, the oxygen transport capacity of this composite OC can reach up to 0.056 g O2/g OC. Density functional theory calculations have been carried out to analyze the changes in reactivity and stability of the mixed-oxide OC. When a Mn3O4(001) surface adsorbs a Cu4O4 cluster, the average bond length of Cu-O in the Cu4O4 cluster increases from 1.983 to 2.047 Å and the charge is transferred from Cu4O4 to Mn3O4(001). Chemical reaction between the cluster and the surface occurs, and Cu-Mn composite oxides are formed after adsorption. Moreover, the adsorption energy is -3.749 eV, which is higher than that of Cu4O4 on a CuO(111) surface (-2.92 eV), and the composite OC has better stability and sintering resistance than the Cu OC. The stability of the composite OC was also investigated at 900 °C under reducing conditions and at 700 °C under oxidizing conditions. The results show that the Cu-Mn/Zr composite OC remains stable over 15 consecutive cycles. Moreover, the Cu-Mn composite does not only reduce the oxygen uncoupling temperature of CuO but it also overcomes thermodynamic limitations of the oxidation of Mn3O4 to Mn2O3, where the redox reaction of the Cu-Mn composite OC can be expressed as follows: CuxMn3-xO4 ⇋ CuxMn2-x + O2(g). From the results, it can be concluded that Mn2O3 is the most suitable composite oxide to improve the oxygen uncoupling properties of a Cu OC for oxygen uncoupling in the CLAS system.

Anxiety disorder is highly prevalent worldwide and represents a chronic and functionally disabling condition, with high levels of psychological stress characterized by cognitive and physiological symptoms. Scopoletin (SP), a main active compound in Angelica dahurica, is traditionally used for the treatment of headache, rhinitis, pain, and other conditions. Here, we evaluated the effects of SP in a mouse model of complete Freund’s adjuvant (CFA)-induced chronic inflammation anxiety. SP (2.0, 10.0, 50.0 mg/kg) administration for 2 weeks dose-dependently ameliorated CFA-induced anxiety-like behaviors in the open field test and elevated plus maze test. Moreover, we found that SP treatment inhibited microglia activation and decreased both peripheral and central IL-1β, IL-6, and TNF-α levels in a dose-dependent manner. Additionally, the imbalance in excitatory/inhibitory receptors and neurotransmitters in the basolateral nucleus after CFA injection was also modulated by SP administration. Our findings indicate that the inhibition of the nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways involving anti-inflammatory activities and regulation of the excitatory/inhibitory balance can be attributed to the anxiolytic effects of SP. Moreover, our molecular docking analyses show that SP also has good affinity for gamma-aminobutyric acid (GABA) transaminase and GABAA receptors. Therefore, these results suggest that SP could be a candidate compound for anxiolytic therapy and for use as a structural base for developing new drugs.

Four mononuclear cyclometalated iridium(III) complexes, namely, [Ir(FQ)(L1)2] (Ir-1), [Ir(FQ)(L2)2] (Ir-2), [Ir(FQ)(L3)2] (Ir-3) and [Ir(FQ)(L4)2]·2CH3OH (Ir-4) using 5-fluoro-8-quinolinol (H-FQ)-based ligands and [(C^N)2IrCl(μ-Cl)]2 precursor have been first synthesised. The two most effective complexes (containing 7,8-benzoquinoline (H-L3) and 1-phenylpyrazole (H-L4)), Ir-3 and Ir-4, kill HeLa cells in the nanomole range, with the IC50 values of 0.170 ± 0.05 and 0.035 ± 0.002 μM, respectively, indicating that they could potentially inhibit HeLa tumour populations at a lower concentration. Encouragingly, Ir-3 and Ir-4 induce HeLa apoptosis, as indicated by the clear changes in the apoptosis-associated proteins; both accumulate to a high extent in the mitochondrial fraction; promote mitochondrial membrane (MMP) depolarisation and loss of MMP; and trigger caspase-mediated mitochondrial dysfunction apoptosis pathways. To the best of our knowledge, this study is the first to synthesize cyclometalated iridium(III)-5-fluoro-8-quinolinol complexes that can function as mitochondrion-targeting anticancer drugs.

We recently published that type 2 diabetes promotes cell centrosome amplification via upregulation of Rho-associated protein kinase 1 (ROCK1) and 14-3-3 protein-σ (14-3-3σ). This study further investigates the molecular mechanisms underlying diabetes-associated centrosome amplification. We found that treatment of cells with high glucose, insulin, and palmitic acid levels increased the intracellular and extracellular protein levels of Wingless-type MMTV integration site family member 6 (Wnt6) as well as the cellular level of β-catenin. The treatment also activated β-catenin and promoted its nuclear translocation. Treatment of cells with siRNA species for Wnt6, Frizzled-4 (FZD4), or β-catenin as well as introduction of antibodies against Wnt6 or FZD4 to the cell culture medium could all attenuate the treatment-triggered centrosome amplification. Moreover, we showed that secreted Wnt6-FZD4-β-catenin was the signaling pathway that was upstream of ROCK1 and 14-3-3σ. We found that advanced glycation end products (AGEs) were also able to increase the cellular and extracellular levels of Wnt6, the cellular protein level of β-catenin, and centrosome amplification. Treatment of the cells with siRNA species for Wnt6 or FZD4 as well as introduction of antibodies against Wnt6 or FZD4 to the cell culture could all inhibit the AGEs-elicited centrosome amplification. In colon tissues from a diabetic mouse model, the protein levels of Wnt6 and 14-3-3σ were increased. In conclusion, our results showed that the pathophysiological factors in type 2 diabetes, including AGEs, were able to induce centrosome amplification. It is suggested that secreted Wnt6 binds to FZD4 to activate the canonical Wnt6 signaling pathway, which is upstream of ROCK1 and 14-3-3σ, and that this is the cell signaling pathway underlying diabetes-associated centrosome amplification.

In the present investigation, a new Ag–ZnO loaded carboxymethyl cellulose/K-carrageenan/graphene oxide/konjac glucomannan (Ag–ZnO@CGK) hydrogel was effectively prepared by means of a straight forward two step technique for clinical applications as wound-recuperating materials. In the first step, silver nanoparticles were synthesized with green deoxidizer mango peel extracts. The Ag–ZnO@CGK hydrogel indicated incredible swelling assimilation and impressive mechanical properties. Also, Ag–ZnO@CGK hydrogel exhibited great bactericidal movement against test microorganisms. In vitro viability testing demonstrated that fibroblast cells could endure well within the sight of Ag@CGK hydrogel, showing that Ag–ZnO@CGK hydrogel has great viability. In vivo animal models demonstrated that the Ag–ZnO@CGK hydrogel adequately quickened wound recuperating and histological examinations demonstrated that they have advanced fibroblast development and quickened epithelialization. The test results demonstrated that Ag–ZnO@CGK hydrogel has incredible potential in advanced wound healing.

The growing demand of propene and its derivatives promotes the development of on-purpose propene production technology. Chemical looping oxidative dehydrogenation of propane (CL-ODHP) is an alternative with several advantages. The research in this paper focuses on selecting suitable oxygen carrier for CL-ODHP process by a comprehensive thermodynamic method. The Gibbs free energy changes of propane oxidative dehydrogenation reactions to temperature for 45 different oxygen carriers are calculated to evaluate their reactivity and availability for propane oxidative dehydrogenation. Meanwhile, the chemical stability including gas oxygen releasing and hydroxides formation of different oxygen carrier systems are considered. Furthermore, the Gibbs free energy minimization method is used to calculate the equilibrium compositions of CL-ODHP reactions system considering side reactions. And propane conversion and propene selectivity of different oxygen carriers under different conditions are obtained. Other important properties are also qualitatively estimated. Among the studied oxygen carriers, Mn-based and Mo-based oxygen carriers would be more suitable for CL-ODHP process than others. And Al2O3, SiO2, TiO2, ZrO2 and Y2O3 can be the suitable binder candidates.

In this study, we investigated the role of ubiquitin-specific protease 22 (USP22) in the growth and progression of gastric cancer (GC). USP22 mRNA and protein levels were significantly higher in GC tissue samples and GC cell lines than in adjacent noncancerous tissue samples and a normal gastric mucosal epithelial cell line (GES1), respectively. USP22 knockdown significantly decreased in vitro survival, proliferation, migration, and invasiveness of GC cells compared with the controls. Western blot analysis of control and USP22-silenced GC cells showed that USP22 modulates the c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling pathways. Subcutanenous injection of USP22-silenced GC cells into SCID mice generated significantly smaller xenograft tumors than did control cells. Moreover, USP22-silenced GC cells showed less lung metastasis than the controls following tail vein injection in SCID mice. In addition, high USP22 expression correlated positively with tumor size, advanced stage and metastasis, and correlated negatively with tumor differentiation and prognosis in GC patients. These results show that USP22 regulates growth and progression of GC via the c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling pathways.

Hepatic fibrosis is the final pathway of several chronic liver diseases, which is characterized by the accumulation of extracellular matrix due to chronic hepatocyte damage. Activation of hepatic stellate cells and oxidative stress (OS) play an important role in mediating liver damage and initiating hepatic fibrosis. Hence, hepatic fibrosis can be reversed by inhibiting multiple channels such as oxidative stress, liver cell damage, or activation of hepatic stellate cells. Liuwei Wuling Tablets is a traditional Chinese medicine formula with the effect of anti- hepatic fibrosis, but the composition and mechanism of reversing hepatic fibrosis are still unclear. Our study demonstrated that one of the main active components of the Chinese medicine Schisandra chinensis, schisandrin C (Sin C), significantly inhibited oxidative stress and prevented hepatocyte injury. Meanwhile one of the main active components of the Chinese medicine Curdione inhibited hepatic stellate cell activation by targeting the TGF-β1/Smads signaling pathway. The further in vivo experiments showed that Sin C, Curdione and the combination of both have the effect of reversing liver fibrosis in mice, and the combined effect of inhibiting hepatic fibrosis is superior to treatment with Sin C or Curdione alone. Our study provides a potential candidate for multi-molecular or multi-pathway combination therapies for the treatment of hepatic fibrosis and demonstrates that combined pharmacotherapy holds great promise in the prevention and treatment of hepatic fibrosis.

ObjectiveTo characterize the serum metabolomic profile and its role in the prediction of poor ovarian response (POR).Patient(s)Twenty-five women with normal ovarian reserve (24-33 years, antral follicle count [AFC] ≥5, anti-Müllerian hormone [AMH] ≥1.2 ng/ml) as the control group and another twenty-five women with POR (19-35 years, AFC ResultsA total of 538 different metabolites were finally identified in the two groups. Tetracosanoic acid, 2-arachidonoylglycerol, lidocaine, cortexolone, prostaglandin H2,1-naphthylamine, 5-hydroxymethyl-2-furancarboxaldehyde, 2,4-dinitrophenol, and D-erythrulose1-phosphate in POR were significantly different from control as were most important metabolites in support vector machines (p <0.05). Metabolomic profiling, together with support vector machines and pathway analysis found that the nicotinate and nicotinamide metabolism pathway, including L-aspartic acid, 6-hydroxynicotinate, maleic acid, and succinic acid semialdehyde, was identified to have significant differences in POR women compared to control women, which may be associated with ovarian reserve.ConclusionThis study indicated that LC–MS-based untargeted metabolomics analysis of serum provided biological markers for women with POR. The nicotinate and nicotinamide metabolism pathway may offer new insight into the complementary prediction and therapeutic potential of POR. The functional associations of these metabolites need further investigation.