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A new gold(i) self-relay catalysis consisting of a 3,3-rearrangement, Nazarov cyclization and Michael addition cascade of 1,3-enyne acetates with aurones and their derived azadienes is reported, producing functionalized cyclopentenones.

8-methylene-tert-butylamine-3',5,7-trihydroxy-4'-methoxyflavanone (MTBH), a novel hesperidin derivative, has potential in the prevention of hepatic disease, however, its effects on cytochrome P450 isoforms (P450s) remains unexplored. The purpose was to investigate the effects of MTBH on the mRNA, protein levels and activities of six P450s (1A2, 2C11/9, 2D2/6, 3A1/4, 2C13/19 and 2E1) in vitro and in vivo.In vitro study, rat and human liver microsomes were adopted to elucidate the inhibitory effect of MTBH on six P450s using probe drugs. In vivo study, Sprague-Dawley male rats were treated with MTBH (25, 50 or 100 mg/kg for 28 consecutive days), phenobarbital (80 mg/kg for 12 consecutive days) or 0.5% CMC-Na solution (control group) by intragastric administration, then, the mRNA, protein levels and activities of liver P450s were analyzed by real-time PCR, western blotting and probe-drug incubation systems, respectively.The in vitro study indicated that MTBH inhibits the activities of CYP3A1/4 and CYP2E1 in rat and human liver microsomes. In vivo data showed that MTBH inhibits mRNA, protein levels and activities of CYP3A1 and CYP2E1 in medium- and high-dose MTBH groups.MTBH has the potential to cause drug-drug interactions when co-administered with drugs that are metabolized by CYP3A1/4 and CYP2E1.

Recent studies have reported that MLST8 is upregulated in many malignant tumors. Nevertheless, the underlying molecular mechanism is still unclear. The aim of this work was to investigate how MLST8 contributes to the development and progression of clear cell renal cell carcinoma (ccRCC). MLST8 is an oncogenic protein in the TCGA database and ccRCC clinical specimens. We also ascertain that MLST8 interacts with FBXW7, which was universally regarded as an E3 ubiquitin ligase. MLST8 can be degraded and ubiquitinated by tumor suppressor FBXW7. FBXW7 recognizes a consensus motif (T/S) PXX (S/T/D/E) of MLST8 and triggers MLST8 degradation via the ubiquitin‐proteasome pathway. Strikingly, the activated cyclin dependent kinase 1 (CDK1) kinase engages in the MLST8 phosphorylation required for FBXW7‐mediated degradation. In vitro, we further prove that MLST8 is an essential mediator of FBXW7 inactivation‐induced tumor growth, migration, and invasion. Furthermore, the MLST8 and FBXW7 proteins are negatively correlated in human renal cancer specimens. Our findings suggest that MLST8 is a putative oncogene that functions via interaction with FBXW7, and inhibition MLST8 could be a potential future target in ccRCC treatment., Schematic diagram of the CDK1‐FBXW7α signaling axis in the regulation of MLST8 protein degradation.

Daphnenoids A-C (1-3), three unusual sesquiterpenes with distinctive ring skeletons, together with a biogenetically related daphnenoid D (4) were obtained from the herb of Daphne penicillata by molecular networking strategies. Daphnenoid A (1) possesses a unique caged tetracyclo [5.3.2.01,6.04,11] dodecane scaffold by unexpected cyclizations of C-1/C-11 and C-2/C-14. Daphnenoids B and C (2 and 3) were the first discovered natural sesquiterpenes with unique 5/5 spirocyclic systems in nature. Their structures were determined by NMR spectroscopic analysis, computer-assisted structure elucidation methods, quantum chemical calculations, and X-ray diffraction. A hypothetical biogenetic pathway begins with typical guaiane sesquiterpene (a), including a key intermediate (4) was proposed. Daphnenoids B and C (2 and 3) exhibited potential inhibitory activities on the production of NO against LPS-induced BV2 microglial cells.

Nowadays, there is an urgent need for microwave absorbing materials with light weight, thin thickness, and strong absorbing ability to solve the problem of electromagnetic radiation. In this study, we report a novel high-performance aerogel absorber by growing MoO3-doped WO3 nanoflakes on reduced graphene oxide (rGO) sheets. The resultant rGO-Mo-WO3 aerogel displays a low density (∼75 mg/cm3) and unique hierarchical architectures including 3D porous microstructures, 2D rGO skeleton, and binary transition metal oxide of Mo-WO3 nanoflakes, thus leading to excellent microwave absorption performances. Typically, rGO-Mo-WO3 aerogel exhibits an ultra-strong reflection loss (RL) of −61.8 dB with a thin coating thickness of 1.54 mm. And a wide effective absorption bandwidth of 6.24 GHz can be achieved at a low filler loading of 8 wt%, much superior to previous ones. The synergistic effect of moderate polarization relaxation loss and weak conduction loss together with the porous microstructure for the aerogel result in the suitable impedance matching and strong microwave attenuation ability. This work may demonstrate a promising method to fabricate hierarchically nanostructured absorbers with the advantages of light weight, ultra-strong microwave absorption, and thin coating thickness.

Chitosan (CS) films containing 0, 1, 3 and 5% (w/w) of polyphenol-rich rambutan peel extract (RPE) were developed. The micro-structural characterization and physical and functional properties of the films were determined. Results showed RPE formed strong interactions with CS, making film inner micro-structure become uniform and film crystallinity decline. Amongst different films, CS film containing 5% of RPE showed the lowest light transmission, moisture content (28.35%), water solubility (46.07%), water vapor permeability (8.41 × 10−10 g m−1 s−1 Pa−1) and oxygen permeability (0.28 cm3 mm m−2 day−1 atm−1). Meanwhile, CS film containing 5% of RPE exhibited the highest tensile strength (38.87 MPa) and elongation at break (51.73%) and the strongest antioxidant and antimicrobial activities. Finally, pork was wrapped with the films and stored at 4 °C for 8 days. Results showed pork wrapped with CS film containing 5% of RPE presented the lowest total volatile basic nitrogen level (9.17 mg/100 g), thiobarbituric acid reactive substance value (0.51 mg malondialdehyde/kg) and total viable count (4.53 log colony forming unit/g) and the best sensory attributes on the eighth day. Our results suggested the potential of CS film containing 5% of RPE as an active packaging material in pork preservation.

Oestradiol (E2) is a critical factor for multiple systems' development during the embryonic period. Here, we aimed to investigate the effects of oestradiol on intrahepatic bile duct development, which may allow a better understanding of congenital bile duct dysplasia. DLK+ hepatoblasts were extracted from the C57BL/6CrSlc foetal mice and randomly divided into control group, oestradiol groups (1, 10, 100 nM) and oestradiol (10 nM) + DAPT (inhibitor of Notch signalling; 40 µM) group for in vitro experiments. For in vivo analysis, pregnant mice were divided into control group, oestradiol (intraperitoneal injection of 0.6 mg/kg/day) ± DAPT (subcutaneous injection of 10 mg/kg/day) groups and tamoxifen (gavage administration of 0.4 mg/kg/day) group. The results showed that oestradiol promoted hepatoblast differentiation into cholangiocytes and intrahepatic bile duct development during the embryonic period. Tamoxifen, an antioestrogenic drug, inhibited the above processes. Moreover, oestradiol promoted the expression of Notch signalling pathway‐associated proteins and genes both in vitro and in vivo. Notably, DAPT addition inhibited the oestradiol‐mediated effects. In conclusion, oestradiol can promote hepatoblast differentiation into cholangiocytes and intrahepatic bile duct development of C57BL/6CrSlc mice during embryonic period via the Notch signalling pathway.

circRNAs have been suggested to modulate NSCLC tumorigenesis and drug resistance. Whether circSNX6 affects NSCLC remains unclear. In this study, we aim to investigate the role of circSNX6 in drug resistance of NSCLC exposed to cisplatin. RT-qPCR method was used to investigate expression levels of circSNX6, miR-137 and CXCL12. MTT, cell colony formation and TUNEL assays were utilized to assess cell viability, proliferation, apoptosis, respectively. Xenograft assay was conducted to examine in vivo tumor growth. circSNX6 overexpression caused enhanced cell viability and proliferation of H1299 and Calu-1, while it inhibited apoptosis under cisplatin treatment. miR-137 inhibitor greatly rescued cell viability, proliferation and apoptosis of circSNX6 knockdown H1299 cells. miR-137 mimic increased ROS generation, as well as reduced GSH and SOD levels, whereas miR-137 inhibitor exerted opposing effect. circSNX6 knockdown also enhanced ROS generation, as well as decreased GSH and SOD levels. CXCL12 partially restored miR-137 mimic-modulated cell viability, proliferation and apoptosis. Herein, our group proposes circSNX6 as key regulator for drug resistance of NSCLC. The findings provide solid groundings for understanding of NSCLC pathogenesis and development of therapeutics.

Edaravone (Eda) is a free radical scavenger used in clinical trials for the treatment of ischemic stroke and amyotrophic lateral sclerosis. However, how Eda exerts its neuroprotective effects remains to be elucidated. We investigated the neuroprotective effects of Eda in cultured hippocampal neurons and in a mouse model of AlCl3/D-galactose-induced cognitive impairment. Eda protected hippocampal neurons by eliminating H2O2 or glutamate-induced toxicity, leading to decreased cell viability and neurite shortening. Consistently, Eda restored impaired levels of BDNF, FGF2 and their associated signaling axes (including TrkB, p-Akt and Bcl-2) to attenuate neuronal death. In a mouse model of chemically-induced cognitive impairment, Eda restored the levels of BDNF, FGF2 and TrkB/Akt signaling axis to attenuate neuronal apoptosis, thereby ameliorating cognitive impairment. Meanwhile, the pro-inflammation was eliminated due to the restoration of pro-inflammatory factors such as TNF-α, IL-6, IL-1β, and NOS2. In summary, Eda is an effective drug for protecting neurons from neurotoxic injury. BDNF, FGF2, and their regulated pathways may be potential therapeutic targets for neuroprotection.

The maternal‐foetal interface is an immune‐privileged site where the semi‐allogeneic embryo is protected from attacks by the maternal immune system. Uterine macrophages are key players in establishing and maintaining pregnancy, and the dysregulation of the M1‐M2 subpopulation balance causes abortion. We separated two distinct mouse uterine macrophage subpopulations during early pregnancy, CD45+F4/80+CD206− M1‐like (M1) and CD45+F4/80+CD206+ M2‐like (M2) cells. The M1 preponderance was significantly exaggerated at 6 hours after lipopolysaccharide (LPS) treatment, and adoptive transfer of M2 macrophages partially rescued LPS‐induced abortion. RNA sequencing analysis of mouse uterine M2 versus M1 revealed 1837 differentially expressed genes (DEGs), among which 629 was up‐regulated and 1208 was down‐regulated. Histone deacetylase 9 (Hdac9) was one of the DEGs and validated to be significantly up‐regulated in uterine M2 as compared with M1. Remarkably, this differential expression profile between M1 and M2 was also evident in primary splenic macrophages and in vitro polarized murine peritoneal, bone marrow–derived and RAW 264.7 macrophages. In Hdac9/HDAC9 knockout RAW 264.7 and human THP‐1–derived macrophages, the expression of M1 differentiation markers was unchanged or decreased whereas M2 markers were increased compared with the wild‐type cells, and these effects were unrelated to compromised proliferation. Furthermore, Hdac9/HDAC9 ablation significantly enhanced the phagocytosis of fluorescent microspheres in M2 Raw 264.7 cells yet decreased the capacity of THP‐1‐derived M1 macrophages. The above results demonstrate that Hdac9/HDAC9 deficiency exaggerates M2 macrophage polarization in mouse and human macrophages, which may provide clues for our understanding of the epigenetic regulation on macrophage M1/M2 polarization in maternal‐foetal tolerance.

In this study, a series of molecular dynamics (MD) simulations are performed for methane-water and methane-brine systems in the range of 263.15 K∼283.15 K, 1 MPa∼10 MPa with the ion mass fraction u...

Recent findings have revealed that exposure to environmental contaminants may result in obesity and pose a health threat to the general public. As the activity of transient receptor potential channels (TRPs) plays a permissive role in adipogenesis, the interactions between TRPs and some food pollutants, i.e. bisphenol A, di (2-ethylhexyl) phthalate, zearalenone, and zeranol at 10 μM were investigated in the present study. TRP-V1,-V3, -C4 and -C6 are reported to be differentially expressed in the adipocyte differentiation, and immunoblotting was performed to quantify changes in these TRPs affected by the pollutants. Our result indicated that the mycoestrogen zeranol or α-zearalanol suppressed the expression of the V1 and C6 isoforms. Subsequently, confocal microscopy was used to measure the calcium inflow repressed by zeranol from 0.1 μM to 10 μM. Oil Red O staining was used to determine the differentiation of 3T3 L1 preadipocytes. Zeranol could suppress the expression of TRP-V1 and -C6 protein and inhibit the associated flow of calcium into the cytosol of 3T3 L1 cells. Its IC50 value for inhibiting calcium inflow stimulated by 40 μM capsaicin or 10 μM GSK1702934A was estimated to be around 6 μM. Reduced TRP-V1 or -C6 activity might result in promoting adipogenesis. In conclusion, this study demonstrated that zeranol could potentiate fat cell differentiation through antagonizing TRP-V1 and –C6 activities.

Evidence suggests constipation precedes motor dysfunction and is the most common gastrointestinal symptom in Parkinson's disease (PD). 5-HT4 receptor (5-HT4R) agonist prucalopride has been approved to treat chronic constipation. Here, we reported intraperitoneal injection of prucalopride for 7 days increased dopamine and decreased dopamine turnover. Prucalopride administration improved motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mouse models. Prucalopride treatment also ameliorated intestinal barrier impairment and increased IL-6 release in PD model mice. However, prucalopride treatment exerted no impact on JAK2/STAT3 pathway, suggesting that prucalopride may stimulate IL-6 via JAK2/STAT3-independent pathway. In conclusion, prucalopride exerted beneficial effects in MPTP-induced Parkinson's disease mice by attenuating the loss of dopamine, improving motor dysfunction and intestinal barrier.

In this work, we have successfully in-situ synthesized Na+ and Co2+ co-doped Li0.9Na0.1Mn1-xCoxPO4/C nanoparticles on the surface of Li2.7Na0.3PO4 self-sacrificing template by the co-precipitation process combined with the hydrothermal method. The crystal lattice structure, crystal appearance and electrochemical parameters are characterized by X-ray diffractometer (XRD), scanning electron microscopy (SEM), galvanostatic charge and discharge test, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). SEM analysis indicates that Li0.9Na0.1Mn0.9Co0.1PO4/C composite shows uniform porous structure and nanosized grain particles. The electrochemical measurements show that the double ions co-doping routine plays a vital influence on the rate capability and electrochemical lithium storage property of LiMnPO4 material. The initial discharge specific capacity of Li0.9Na0.1Mn0.9Co0.1PO4/C reaches 164.3 mAh/g (0.05 C) and 148.0 mAh/g (1 C), respectively. The excellent rate capability is attributed to the synergetic doping effect of Na+ and Co2+ on improving the Li-ion diffusion rate and broadening the Li-ion diffusion channels.

Most nano-scaled adsorbents have trouble in separating from aqueous solution, thus, a need for new materials of facile separation and predominant adsorption performance has arisen. This present study focused on a novel segregative zirconium-chitosan modified sodium alginate (Zr-CTS/SA) composite preparation and its performance for As(III/V) removal from aqueous solution. The obtained composite presented a spherical structure with a diameter of 2.0–3.0 mm and favorable thermal stability. Experimental data showed that Zr-CTS/SA had considerable adsorbability for As(III) and As(V), the adsorption capacities were enhanced about at least 20 and 6 times separately compared with pristine SA beads. The adsorption processes of As(III) and As(V) could both be described with Langmuir isotherm model and the maximum adsorption capacities reached 43.19 and 76.78 mg g−1, respectively. The kinetic data of As(III) followed the intra-particle diffusion model while As(V) fitted the pseudo-first-order model. Moreover, the adsorption mechanisms of As(III/V) involved ligand exchange with Cl on the surface of Zr-CTS/SA, another reaction pathway for As(V) was the electrostatic attraction with protonated -OH and -NH2 groups. Note that the employment of Zr-CTS/SA in low-concentration arsenic solution exhibited a residue concentration as low as the 10 μg L−1 WHO guideline for drinking water.

Rationale: Accumulated evidence indicates that environmental plasticizers are a threat to human and animal fertility. Di (2-ethylhexyl) phthalate (DEHP), a plasticizer to which humans are exposed daily, can trigger reproductive toxicity by acting as an endocrine-disrupting chemical. In mammals, the female primordial follicle pool forms the lifetime available ovarian reserve, which does not undergo regeneration once it is established during the fetal and neonatal period. It is therefore critical to examine the toxicity of DEHP regarding the establishment of the ovarian reserve as it has not been well investigated. Methods: The ovarian cells of postnatal pups, following maternal DEHP exposure, were prepared for single cell-RNA sequencing, and the effects of DEHP on primordial follicle formation were revealed using gene differential expression analysis and single-cell developmental trajectory. In addition, further biochemical experiments, including immunohistochemical staining, apoptosis detection, and Western blotting, were performed to verify the dataset results. Results: Using single-cell RNA sequencing, we revealed the gene expression dynamics of female germ cells and granulosa cells following exposure to DEHP in mice. Regarding germ cells: DEHP impeded the progression of follicle assembly and interfered with their developmental status, while key genes such as Lhx8, Figla, and others, strongly evidenced the reduction. As for granulosa cells: DEHP likely inhibited their proliferative activity, and activated the regulation of cell death. Furthermore, the interaction between ovarian cells mediated by transforming growth factor-beta signaling, was disrupted by DEHP exposure, since the expression of GDF9, BMPR1A, and SMAD3 was affected. In addition, DNA damage and apoptosis were elevated in germ cells and/or somatic cells. Conclusion: These findings offer substantial novel insights into the reproductive toxicity of DEHP exposure during murine germ cell cyst breakdown and primordial follicle formation. These results may enhance the understanding of DEHP exposure on reproductive health.

Background To develop an effective model of predicting fatal outcomes in the severe coronavirus disease 2019 (COVID-19) patients. Methods Between February 20, 2020 and April 4, 2020, consecutive confirmed 2541 COVID-19 patients from three designated hospitals were enrolled in this study. All patients received chest computed tomography (CT) and serological examinations at admission. Laboratory tests included routine blood tests, liver function, renal function, coagulation profile, C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and arterial blood gas. The SaO2 was measured using pulse oxygen saturation in room air at resting status. Independent high-risk factors associated with death were analyzed using Cox proportional hazard model. A prognostic nomogram was constructed to predict the survival of severe COVID-19 patients. Results There were 124 severe patients in the training cohort, and there were 71 and 76 severe patients in the two independent validation cohorts, respectively. Multivariate Cox analysis indicated that age ≥ 70 years (HR = 1.184, 95% CI 1.061–1.321), panting (breathing rate ≥ 30/min) (HR = 3.300, 95% CI 2.509–6.286), lymphocyte count 9/L (HR = 2.283, 95% CI 1.779–3.267), and interleukin-6 (IL-6) > 10 pg/ml (HR = 3.029, 95% CI 1.567–7.116) were independent high-risk factors associated with fatal outcome. We developed the nomogram for identifying survival of severe COVID-19 patients in the training cohort (AUC = 0.900, 95% CI 0.841–0.960, sensitivity 95.5%, specificity 77.5%); in validation cohort 1 (AUC = 0.811, 95% CI 0.763–0.961, sensitivity 77.3%, specificity 73.5%); in validation cohort 2 (AUC = 0.862, 95% CI 0.698–0.924, sensitivity 92.9%, specificity 64.5%). The calibration curve for probability of death indicated a good consistence between prediction by the nomogram and the actual observation. The prognosis of severe COVID-19 patients with high levels of IL-6 receiving tocilizumab were better than that of those patients without tocilizumab both in the training and validation cohorts, but without difference (P = 0.105 for training cohort, P = 0.133 for validation cohort 1, and P = 0.210 for validation cohort 2). Conclusions This nomogram could help clinicians to identify severe patients who have high risk of death, and to develop more appropriate treatment strategies to reduce the mortality of severe patients. Tocilizumab may improve the prognosis of severe COVID-19 patients with high levels of IL-6.

A new class of high-quality ionic organic microcrystals with bright deep-blue luminescence (with up to 60% quantum yield) have been prepared in situ by the protonation of 2,2′-di(pyrid-2-yl)bipheny...

A new photocatalytic three-component annulation of 2-alkynylaryldiazonium tetrafluoroborates with γ-hydroxyl terminal alkynes and sodium metabisulfite is reported using fac-Ir(ppy)3 as the photocatalyst for the first time and used to produce a series of (Z)-thiochromene 1,1-dioxides bearing an exocyclic double bond with moderate to good yields in a highly stereoselective manner. A wide variety of easily available substrates with substituent diversity could successfully participate in this photocatalysis with good functional group tolerance.

Dietary supplementation is prevalent in our daily life, in which tablet form plays an important role due to its long-term stability and cost-effectiveness. In the pharmaceutical industry, coordination polymer-based tablets are widely produced for dietary supplementation. The mechanical properties of such dietary supplements are very crucial for the tableting process and need to be broadly studied. In this study, the mechanical properties of a copper supplement, namely copper glycinate hydrate (Cu[O2CCH2NH2]2·H2O), have been studied via high-pressure synchrotron powder X-ray diffraction and density functional theory calculations. This material is a 1D coordination polymer, and adjacent chains are linked via hydrogen bonding in the structure. The measured bulk modulus (Ko) is ∼13.9 GPa, which is comparable to that of small organic drug crystals and far smaller than that of inorganic dietary supplements. The calculated Young's moduli (13.55–35.75 GPa) indicate a significant elastic anisotropy, and the directional dependent Young's modulus can be substantiated with the underlying atomic structure. Our experimental and calculated results provide useful quantitative information for tableting and formulating this dietary supplement in the pharmaceutical industry.

Objectives To explore the in vivo anti-obesity effect of chikusetsusaponin V and explore the underlying mechanism by transcriptomic and metabonomic methods. Methods The physiological parameters of high-fat-diet induced obese mice administered with or without 25 mg/kg and 100 mg/kg of chikusetsusaponin V by gavage for 16 weeks were recorded. In addition, the RNA-sequencing and UHPLC-Q-TOF techniques were applied to obtain the transcriptomic and metabolomic profiling, respectively. Key findings Chikusetsusaponin V could significantly alleviate the high-fat-diet induced increase in the weight of the whole body and obesity-related organs or tissues, and ameliorate the lipid content in the blood, the lipid accumulation in the livers, as well as the hypertrophy of the fat tissues. Importantly, transcriptomic results revealed that more than 30 genes involved in the pathway which closely associates with obesity, were significantly altered. Moreover, metabolomic data indicated the key differential metabolites enriched in the pathways such as the activated protein kinase signaling pathway which is a vital mediator of obesity and other processes. Conclusions The integrative analysis highlighted that chikusetsusaponin V significantly influenced the activated protein kinase signaling pathway at both transcriptomic and metabolomic levels, thereby exerting anti-obesity effects.

As a key regulator of human physiology and metabolic processes, ribonuclease (RNase) A can be used as an important biomarker for predicting human disease occurrence. Hence, establishing sensitive methods for tracking RNase A activity in vitro and in living cells is of great importance. Herein, we present a convenient fluorescence method assisted by reduced graphene oxide (rGO) and DNAzyme mediated fluorescence signal release for RNase A assay. The fluorescence change of the new method showed a positive linear relation with RNase A concentration in the range from 0.5 pg μL−1 to 1 ng μL−1 with a detection limit of 0.089 pg μL−1. By using this method to screen the effector of RNase A from natural compounds, the natural compound of B6 was found to stimulate RNase A activity in vitro and in vivo, the result of which was supported by the real-time imaging of RNase A in living cells. In summary, this fluorescence method with high sensitivity and specificity provides an alternative for RNase A activity assay and effector screening.

New tunable catalytic [2+2] cycloaddition/silane-mediated conjugate transfer reductions of yne-allenones have been developed, by which substituent-diverse cyclobutarenes with generally good yields were selectively synthesized by adjusting Fe-H and Cu-H catalytic systems. Use of the Fe-H system triggers 1,6-conjugate reduction to dihydrocyclobuta[a]naphthalen-4-ols whereas the Cu-H complex enables 1,4-conjugate reduction to cyclobuta[a]naphthalen-4(2H)-ones.

A novel 3D Eu(iii) metal-organic framework (Eu-MOF-1) formulated as [Eu(L)(H2O)(DMA)] (L = 2-(2-nitro-4-carboxylphenyl)terephthalic acid) has been successfully synthesized under solvothermal conditions and characterized by structural analyses. Eu-MOF-1 displays a new 3D framework containing EuIII ions, ligand L, and coordinated DMA molecules and water molecules. The fluorescence investigations indicate that Eu-MOF-1 emits bright red luminescence, and shows relatively high water stability and outstanding chemical stability under a relatively wide range of pH conditions. It is noteworthy that Eu-MOF-1 can quantitatively detect p-aminophenol (PAP) which is a metabolite of phenylamine in human urine. More significantly, Eu-MOF-1 is the first reported multi-responsive luminescent sensor for detecting the biomarker PAP, and MnVII and CrVI anions with high selectivity, sensitivity, recyclability and relatively low detection limits in aqueous solutions. Furthermore, the possible sensing mechanisms of Eu-MOF-1 for selective sensing have also been explored in detail. Eu-MOF-1 could be an ideal candidate as a multi-responsive luminescent sensor in biological and environmental areas.

Carbon dots (CDs) have been studied for years as one of the most promising fluorescent nanomaterials. Herein, fluorescent CDs excited by visible light emitted red fluorescence with a quantum yield of 32.8% via a facile hydrothermal treatment. In addition to being applied in cell imaging, the as-prepared CDs were also utilized in the detection of ammonia and formaldehyde in aqueous solutions because of their pH-dependent properties, with a low limit of detection of 3.7 nM and 44 μM, respectively. Furthermore, we synthesized flexible and transparent fluorescence films by mixing the as-prepared CDs and PVB powder, which can be utilized to directly detect ammonia gas under visible light according to significant colour changes. Therefore, the as-prepared CDs would have more prominent and influential application in clinical diagnostics and environmental analysis.

Luminescent hydrogels have gained widespread attention in smart devices and sensors, because of their flexibility, functional versatility and excellent optical properties. Herein, we report the construction of a clay–polymer hybrid luminescent hydrogel with co-cross-linked networks via in situ polymerization of N-isopropylacrylamide (NIPA) in the presence of two types of cross-linker, LAPONITE® (Lap) and lanthanide complex, endowing the obtained hydrogel with excellent mechanical strength and luminescent performance. By varying the molar ratio of lanthanide ions, the luminescent colors of the hydrogel can be tailored. Moreover, due to the thermoresponsiveness of the PNIPA, the luminescence intensity of the hydrogel can be regulated reversibly.

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

Background/aim TP53 mutation is recognized as a negative prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). Here, we present the characteristics of TP53 mut DLBCL patients following investigation of the effect of a treatment approach on survival of TP53 mut DLBCL patients. Methods A total of 44 DLBCL patients with TP53 mut and treated with an R-CHOP regimen were included for analysis. Patients who failed to achieve a complete response (CR) to initial treatment or relapsed in the first 6 months after initial CR were deemed to have primary refractory disease. Results Among 44 patients harboring TP53 mutations who underwent upfront R-CHOP or R-CHOP-like treatment, 21 (47.7%) had limited-stage and 23 (52.3%) presented advanced-stage disease. Apart from the seven patients receiving upfront surgical resection, 37 had measurable disease under the R-CHOP regimen, with 59.1% (n=26) developing primary refractory disease. Seven limited-stage patients after early complete resection and one with residue resection remained event-free at median follow-up of 37 months. Multivariate analysis revealed that elevated baseline lactate dehydrogenase (LDH), extranodal involvement (two or more), Ann Arbor stage, and locoregional treatment (surgery or radiation therapy) were independent indicators for progression-free survival (PFS). After adjustment for baseline LDH and extranodal involvement, adding locoregional treatment including surgery and radiation to the R-CHOP regimen significantly improved PFS (p=0.008) and overall survival (p=0.017) in limited-stage TP53 mut DLBCL patients compared to R-CHOP-only treatment. Conclusion This study presents the characteristics of TP53-mutated DLBCL and implies a potential benefit of locoregional treatment in limited-stage DLBCL patients with TP53 mutations.

The purpose of this study was to identify the fractal dimension and their relationships with alkalinity properties of soils, and to evaluate the potential of fractal dimension as an indicator of alkalinity properties of soil. Six soils with an increasing salinity (electrical conductivity was 0.09, 0.18, 0.62, 0.78, 1.57 and 1.99 dS m−1, respectively) were selected from the western part of the Songnen Plain (China). Salt content, exchangeable sodium percentage, sodium adsorption ratio and other properties of the soils were determined and the soil particle-size distribution (0–2000 μm) was measured using a laser diffraction particle size analyser. Our results show that the overall fractal dimension of the selected soils ranged from 2.35 to 2.60. A linear regression analysis showed a significant negative correlation between fractal dimension and the amount of coarse sand and fine sand (r = − 0.5452, P P P P P 3− (P

Anthocyanins and betacyanins are two different types of natural pigments. In this study, active and intelligent packaging were prepared by adding anthocyanins or betacyanins or anthocyanins/betacyanins mixture (in the weight ratios of 3:1, 1:1 and 1:3) into starch/polyvinyl alcohol (PVA) films. The physical and functional properties of developed films were compared. Results showed anthocyanins were more pH-sensitive than betacyanins. However, betacyanins were more beneficial to improve the compactness of the films and had stronger hydrogen bonding interactions with film matrix as compared with anthocyanins. The addition of anthocyanins and/or betacyanins slightly decreased the crystallinity of the films but significantly increased the ultraviolet-visible light barrier, water vapor barrier, antioxidant, antimicrobial, and ammonia-sensitive properties of the films. Moreover, the barrier, antioxidant and antimicrobial properties of the films increased with the increase of betacyanins proportion. Amongst different films, the film containing anthocyanins/betacyanins mixture in the weight ratio of 1:3 presented obvious color changes when the film was utilized to monitor the freshness of pork. Our results suggested betacyanins was more beneficial to enhance the barrier, antioxidant and antimicrobial properties of starch/PVA films. Starch/PVA films simultaneously added with anthocyanins and betacyanins were more suitable to monitor the freshness of pork.

Melatonin (N-acetyl-5-methoxytryptamine) plays important roles in plant defences against a variety of biotic and abiotic stresses, including UV-B stress. Molecular mechanisms underlying functions of melatonin in plant UV-B responses are poorly understood. Here, we show that melatonin effect on molecular signalling pathways, physiological changes and UV-B stress resistance in Arabidopsis. Both exogenous and endogenous melatonin affected expression of UV-B signal transduction pathway genes. Experiments using UV-B signalling component mutants cop1-4 and hy5-215 revealed that melatonin not only acts as an antioxidant to promote UV-B stress resistance, but also regulates expression of several key components of UV-B signalling pathway, including ubiquitin-degrading enzyme (COP1), transcription factors (HY5, HYH) and RUP1/2. Our findings indicate that melatonin delays and subsequently enhances expression of COP1, HY5, HYH and RUP1/2, which act as central effectors in UV-B signalling pathway, thus regulating their effects on antioxidant systems to protect the plant from UV-B stress.

An efficient and practical approach to electrophilic thiolation was developed by using commercially available triphosgene as a reductant and the appropriate alkyl- or arylsulfinates, which were transformed in situ into electrophilic RSCl intermediates in the presence of triphosgene. This procedure represents a general and powerful approach for the synthesis of α-(trifluoromethyl)thio-substituted ketones and thiolated electron-rich heteroaromatic compounds.

A study was performed to investigate monomethylamine (MMA) as an alternative or supplementary reagent for selective non-catalytic reduction (SNCR) of nitrogen oxides (NOx) for power plants especially the coal-fired type. A detailed chemical kinetics mechanism for MMA, related to the SNCR NOx reduction process, was modeled using a simplified plug flow reactor (PFR) approach using the CHEMKIN software. Model validation results were in line with reported experimental results. A model sensitivity analysis showed that the normalized MMA/NO stoichiometric ratio (NSR) and the initial NOx concentration are the most critical parameters that significantly affect MMA-based process performance. Additionally, a reduced reaction mechanism and its mechanism tree for this particular process are proposed, consisting of only 18 reactions and 21 species. Simulation comparisons with three other reagents (ammonia, urea, and cyanuric acid), under similar process conditions, indicate that MMA-based SNCR NOx reduction process has a superior performance at much lower temperatures (under 800 K) than conventional SNCR processes, with the added benefit that it does not suffer from ammonia slip problems. The MMA-based SNCR NOx removal system could be applied in cascade mode with other post-combustion NOx removal approaches to extend NOx control to lower temperatures and eliminate the temperature window limitation and potential ammonia slip of conventional SNCR systems. The cascade design is a perfect solution for coal power plants especially at partial load modes of operation which provides more flexibility in performance for such plants. The results of the simulations in this study show that the potential of MMA for SNCR NOx reduction systems at full-scale power plants has significant merit.

Ribosome recycling is the final step of the cyclic process of translation, where the post-termination complex (PoTC) is disassembled by the concerted action of ribosome recycling factor (RRF) and elongation factor G (EF-G) in the sub-second time range. Since, however, both the RRF and PoTC display highly dynamic action during this process, it is difficult to assess the molecular details of the interactions between the factors and the ribosome that are essential for rapid subunit separation. Here we characterized the molecular dynamics of RRF and PoTC by combined use of molecular dynamics simulations, single molecule fluorescence detection and single-particle cryo-EM analysis, with time resolutions in the sub-millisecond to minute range. We found that RRF displays two-layer dynamics: intra- and inter-molecular dynamics during ribosome splitting. The intra-molecular dynamics exhibits two different configurations of RRF: 'bent' and 'extended'. A single-site mutant of RRF increases its propensity to the 'extended' conformation and leads to a higher binding affinity of RRF to the PoTC. The inter-molecular dynamics between RRF and EF-G in the PoTC reveals that the domain IV of EF-G pushes against the domain II of RRF, triggering the disruption of the major inter-subunit bridge B2a, and catalyzes the splitting.

Two new Zn(II)-based coordination polymers {[Zn3(L1)6(H2O)]∙(H2O)4}n (1, HL1 = 4-(tetrazol-5-yl)phenyl-4,2′:6′,4″-terpyridine) and [Zn2Cl2(L2)2H2O]n (2, HL2 = 4-([2,2′:6’,2″’-terpyridin]-4′-yl)benzoic acid) have been successfully prepared using two similar organic ligands with distinct donor groups under similar reaction conditions. The distinct structural features and donor atoms make the two complexes show different water stability, and the complex 1 with good water stability, which can be utilized as the sensor for Fe3+ ion detection in water. The value of Stern–Volmer quenching constant of 1 to the Fe3+ is 5.77 × 104 M− 1, which lies in the top region of the reported CP-based sensors. The mechanism investigation reveals that the energy transfer of resonance from the complex 1 to the Fe3+ ion can account for its fluorescent quenching behavior. The treatment activity of compounds 1 and 2 on the postpartum hemorrhage (PPH) was assessed. First, the cytotoxicity of compounds 1 and 2 on human umbilical vein endothelial cells was assessed with Cell Counting Kit-8 detection kit. Then, to evaluate the prevention of compounds 1 and 2 on the PPH, we conducted the Lowry method and detected the clotting factor IX and anticoagulant factor III contents after the indicated treatment. Finally, the inflammatory response in mice was determined by ELISA method, and the IL-6 and IL-8 levels were determined.

Objectives To investigate plasma and urinary kynurenine (KYN)-tryptophan (TRP) ratios in bladder cancer, expression of indoleamine 2,3-dioxygenase 1 (IDO1) in relation to tryptophan 2,3-dioxygenase (TDO2) in bladder tumour, and the correlation of KYN-TRP ratio with bladder tumour burden. Methods Metabotyping of the TRP-KYN metabolic axis was performed via a clinical case-control study. Expression of IDO1 and TDO2 was measured in human biopsied tissues. Correlational experiments between KYN-TRP ratio and bladder tumour were performed using a murine orthotopic prostate-specific antigen (PSA)-secreting MB49 bladder cancer model. Results We established for the first time that plasma TRP level was significantly decreased, while both plasma and urinary KYN-TRP ratios were significantly higher in bladder cancer patients, and expression level of IDO1 but not TDO2 was increased in human bladder tumour. We reported the positive correlation between IDO1 expression, KYN-TRP ratio, normalized PSA to creatinine, and bladder tumour burden in the murine model. Conclusion Kynurenine-tryptophan ratio is a promising surveillance biomarker for bladder cancer, but would require further validation before clinical translation.

Multifunctional food packaging was prepared by incorporating betalains-rich vegetable amaranth (Amaranthus tricolor L.) extract into quaternary ammonium chitosan (QC)/fish gelatin (FG) blend films. The structures, physical and functional properties of the films with and without amaranth extract (AE) were determined. Results showed betalains-rich AE was pH-sensitive and could change its colors under alkaline conditions. Structural characterization revealed the interactions between AE and film matrix were based on hydrogen bonds, which influenced the compactness of the films. Notably, AE significantly enhanced the thickness (from 0.076 to 0.089 mm), UV–vis light barrier ability, elongation at break (from 66.7% to 88.8%), 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (from 6.8% to 95.8% at 5 mg/mL), antimicrobial activity against four foodborne pathogens (Escherichia coli, Staphylococcus aureus, Salmonella typhimurium and Listeria monocytogenes) and ammonia sensitivity of the films. However, AE remarkably reduced the water vapor permeability (from 34.9 × 10−11 to 26.4 × 10−11 g m−1 s−1 Pa−1) of the films. Notably, the films containing 5 wt% and 10 wt% of AE were suitable to monitor the freshness of shrimp. Our results suggested QC/FG films with betalains-rich AE could be used as antioxidant, antimicrobial and intelligent packaging in food industry.

In the current study, silver nanoparticles (AgNPs) were bio-fabricated with the help of aqueous silver nitrate and green apple (Malus Domestica) extract as a precursor and reducing agent, respectiv...