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Photodynamic therapy (PDT) is a non-invasive method for cancer treatment that relies on the generation of excess reactive oxygen species (ROS), upon excitation of photosensitizer (PS), to eradicate tumor cells. However, the overexpress of endogenous antioxidants in tumor cells will eliminate the ROS and restrict the therapeutic efficacy of PDT. Herein, a novel type of PS was developed by conjugating cinnamaldehyde (CA), a kind of oxidative stress amplified agent, with porpholactam through a hydrazone bond. The new PS retains the photophysical properties of porpholactam, which displays high singlet oxygen quantum yield for the PDT function. The results of in vitro experiments performed including ROS assay and the cytotoxicity in cancer cells suggest that the rational design of the novel porpholactam-CA derivatives result in enhanced ROS generation upon irradiation, providing a possible approach to achieve enhanced therapeutic effects in PDT.

In this study, we have established a convenient and efficient approach named Modification of DNA Regions with Metagenomic DNA Fragments (MDRMDF) for protein engineering. Degenerate primers were designed corresponding to conserved regions of the gene of interest which were used for amplification of fragments with template of the metagenomic DNA. The resulting PCR products were used to replace the corresponding regions of the gene of interest to introduce modified gene for function-based screening. Therefore, this method can make full use of the metagenomic DNA sequences with unknown metagenomic gene information for efficient protein engineering. The β-xylosidase BH3683 was used to construct a MDRMDF library which was screened with a newly designed p-NPX-M9 medium-based strategy. As a result, a mutant protein Xyl-M56 showing high activity, improved pH stability and higher tolerance to organic solvents was obtained which may have potential for industrial application. The MDRMDF method may find wide application in enzyme engineering, metabolic engineering and other fields, especially offering a new methodological option for the directed evolution of proteins.

Background FOLFIRINOX and gemcitabine plus albumin-bound paclitaxel (AG) regimens are recommended as first-line therapy for both locally advanced and metastatic pancreatic cancer. However, there were no specific markers to conduct personalized regimen choice. The research is to assess delta Housfield unit (delta HU), which is the difference in CT attenuation value (in HU) between enhanced and nonenhanced phase of region of interest, as a marker for predicting chemotherapy response of unresectable pancreatic cancer. Methods A total of 179 unresectable pancreatic cancer patients were enrolled in the study. Kaplan-Meier analysis and COX regression analysis were performed for progression-free survival (PFS) and overall survival. The differences of clinical characteristics were analyzed by χ 2test. Microvessel density (MVD) was calculated by immunochemistry staining of CD34. Results Delta HU was an independent risk factor for unresectable pancreatic cancer (P = 0.017, HR 0.672, 95%CI 0.485–0.930). Patients with higher delta HU were associated with better PFS (P = 0.004). For modified FOLFIRINOX (mFOLFIRINOX) group, delta HU was an independent risk factor (P = 0.045, HR 0.571), but not for AG group (P = 0.473, HR 0.855). Delta HU was correlated with stroma MVD (P = 0.000, R = 0.483), not with parenchyma MVD (P = 0.074, R = 0.199). Conclusions Delta HU was a marker predicting chemotherapy response for unresectable pancreatic cancer. Higher delta HU was associated with better survival for patients receiving mFOLFIRINOX rather than AG. The delta HU was positively correlated with stroma MVD, explaining the relationship between delta HU and prognosis.

Salmonella, being one of the most widespread foodborne pathogens, is a compulsory test item required by national food safety standard of China and many other countries. More sensitive and specific Salmonella detection method is still needed since traditional methods are time consuming and highly dependent on enormous manpower and material resources. In this research, a bacteria detection method based on CRISPR-Cas13a system (where CRISPR is Clustered Regularly Interspaced Short Palindromic Repeats) was proposed. The target DNA was amplified by PCR and transcribed into RNA by T7 transcriptase, which can activate the RNase activity of the Cas13a protein. The self-folding quenched fluorescent probe can be cleaved by the activated Cas13a protein to generate fluorescent signal. We named this method as PCF detection (PCR-CRISPR-Fluorescence based nucleic acid detection). In this study, PCF detection showed excellent sensitivity, which can detect Salmonella genomic DNA with a minimum of 101 aM or 10° CFU/ml Salmonella bacteria in 2 hr. It also showed good specificity with no cross-reaction with other common foodborne bacteria. PRACTICAL APPLICATION: The PCF detection method proposed in this article can detect Salmonella sensitively and specifically, providing a novel strategy for the detection of foodborne pathogens in food and has great application potential in other microbial detection fields.

The study of lanthanide (Ln)-transition-metal (TM) heterometallic clusters which play key roles in various high-tech applications is a rapid growing field of research. Despite the achievement of numerous Ln-TM cluster compounds comprising one Ln atom, the synthesis of Ln-TM clusters containing multiple Ln atoms remains challenging. Here, we present the preparation and self-assembly of a series of Au-bridged heterometallic clusters containing multiple cerium (Ce) atoms via on-surface coordination. By employing different pyridine and nitrile ligands, the ordered coordination assemblies of clusters containing 2, 3 and 4 Ce atoms bridged by Au adatoms are achieved on Au(111) and Au(100), as revealed by scanning tunneling microscopy. Density functional theory calculations uncover the indispensable role of the bridging Au adatoms in constructing the multi-Ce-containing clusters by connecting the Ce atoms via unsupported Ce-Au bonds. These findings demonstrate on-surface coordination as an efficient strategy for preparation and organization of the multi-Ln-containing heterometallic clusters., The preparation of lanthanide-transition metal clusters containing multiple lanthanide atoms remains challenging. Here, the authors present the controlled on-surface formation of ligand-stabilized heterometallic Ce/Au clusters containing two, three and four Ce atoms bridged by Au adatoms.

Homoleptic tris(6,6′-dimethyl-2,2′-bipyridine) rare earth metal complexes M(κ2-dmbp)3 (M = Y, Tb, Dy, Ho, Er; dmbp = 6,6′-dimethyl-2,2′-bipyridine) were synthesized by in situ reduction of 3 equiv. of dmbp with excess KC8 in the presence of 1 equiv. of rare earth metal trihalides. All compounds were characterized by X-ray crystallography, UV-Vis-NIR spectroscopy, infrared (IR) spectroscopy, elemental analysis, and magnetic measurements. While the structural parameters and spectroscopic data confirmed the existence of the trivalent rare earth metal cation and three dmbp radical anions, the electron paramagnetic resonance (EPR) spectrum and the measured magnetic moment of Y(κ2-dmbp)3 indicated that two parallel dmbp radical anions were antiferromagnetically coupled. For paramagnetic rare earth metal ions, room temperature magnetic susceptibility values indicated a weak ferromagnetic interaction between the metal ion and the remaining dmbp radical. Density functional theory (DFT) calculations were performed on Y(κ2-dmbp)3 to gain insight into the electronic structures of these homoleptic metal complexes. The computational results were consistent with the structural, spectroscopic, and magnetic data for a S = 1/2 ground state and spin densities mostly residing on one dmbp radical anion, while the spins on the other two parallel dmbp radical anions being antiferromagnetically coupled.

A series of mononuclear lanthanide complexes with the formula [Hex4N][Ln(DBM)4] (1Ln) (Ln = Nd and Tb), [But4N][Dy(DBM)4] (2), [Et4N][Dy(DBM)4] (3), [PhCH2N(CH3)3][Dy(DBM)4] (4) and [Hex4N][Dy(TTA)4] (5) formed by four β-diketonate ligands (i.e. DBM = dibenzoylmethane, TTA = 2-thenoyltrifluoroacetone) and four organic counter ammonium cations (i.e. Hex4N = tetrahexylammonium, But4N = tetrabutylammonium, Et4N = tetraethylammonium and PhCH2N+(CH3)3) were structurally and magnetically characterized. The organic ammonium as contactless cation pairs with [Ln(β-diketonate)4]−1 moieties, the impact of different remote organic cations and the first coordination sphere comprising distinct β-diketonates on their SMM performance were elaborately studied. This is an efficient method by virtue of the interaction of the remote organic ion pair to modulate their single-molecule magnetic (SMM) properties. More importantly, the tetrakis β-diketonate Dy(III) anion can be almost intactly grafted on functional GaN substrate through an anion exchange reaction, resulting in diminishing slow magnetic relaxation behavior, which presents potential application in future SMM devices.

Transition metal nitrides (TMNs) are predicted to be highly promising electrocatalysts for the nitrogen reduction reaction (NRR) by theoretical calculations. TMNs follow a special Mars-van Krevelen (MvK) mechanism during the NRR, involving surface lattice nitrogen exchange and regeneration. It is hence essential to identify the source of nitrogen, especially taking the stability of lattice nitrogen into consideration. Herein, we investigated the deactivation process of a benchmark CrN nanoparticle catalyst (CrN NPs) with a phase-pure cubic rocksalt (RS) structure for the electrochemical NRR. The current work identifies two possible deactivation pathways for CrN: (i) potential-induced structural collapse of the catalyst including both lattice N leaching and metal dissolution and (ii) ammonia poisoning due to the accumulation and strong chemical bonding of the produced ammonia on the CrN surface. This work provides new perspectives for understanding the structural evolution of nitrogen-containing electrocatalysts for NRR research.

The suppression of irreversible phase change in battery-type materials during electrochemical process, leading to high-performance asymmetric supercapacitors (ASCs), remains one of the crucial challenges for the new generation of electrochemical energy storage devices. Herein, we propose a pre-activation strategy to address the corresponding problem based on an in-depth study of the failure mechanism of nickel–manganese layered double hydroxide (LDH), which is the inhibition of the exfoliation and deactivation of lattice Mn during the cycling process. The modified NiMn-LDH shows enhanced electrochemistry performance compared to pristine NiMn-LDH, with an increase in specific capacity from 855 to 1082 C g−1 and a doubling of stability after 3000 cycles. Furthermore, the assembled ASC device achieves a high specific energy density of 48.9 W h kg−1 at a power density of 810 W kg−1. The anchored, activated lattice Mn provided by hydrogen peroxide in the pre-activation strategy is proved to play a vital role in achieving high-performance ASCs. This work paves a new avenue to solve the long-standing significant challenge of battery-type materials for asymmetric supercapacitors.

Flavonoids have notable biological activities and have been widely used in the medicinal and chemical industries. However, single-copy integration of heterologous pathway genes limits the production of flavonoids. In this work, we designed and constructed single-step integration of multiple flavonoid (2S)-naringenin biosynthetic pathway genes in S. cerevisiae. The efficiency of the naringenin metabolic pathway gene integration into the rDNA site reached 93.7%. Subsequently, we used a high titer p-coumaric acid strain as a chassis, which eliminated feedback inhibition of tyrosine and downregulated the competitive pathway. The results indicated that increasing the supply of p-coumaric acid was effective for naringenin production. We additionally optimized the amount of donor DNA. The optimum strain produced 149.8 mg/L of (2S)-naringenin. The multi-copy integration of flavonoid pathway genes effectively improved (2S)-naringenin production in S. cerevisiae. We further analyzed the copy numbers and expression levels of essential genes (4CL and CHS) in the (2S)-naringenin metabolic pathway by qPCR. Higher copy numbers of the (2S)-naringenin metabolic pathway genes were associated with greater 4CL and CHS transcription, and the efficiency of naringenin production was higher. Therefore, multi-copy integration of genes in the (2S)-naringenin metabolic pathway was imperative in rewiring p-coumaric acid flux to enhance flavonoid production.

The first-row transition metal compounds, [MII(L1)2](ClO4)2 (M = Ni (1); Co (2)), have been prepared by treatment of a neutral tetradentate ligand (L1 = N2,N9-dibutyl-1,10-phenanthroline-2,9-dicarboxamide) with metal perchlorate salts in MeOH. Both compounds have been structurally characterized by X-ray crystallography and it was found that the coordination numbers are 6 and 7, respectively. The reaction of 6,6′-bis(2-tbutyl-tetrazol-5-yl)-2,2′-bipyridine (L2) with hydrated FeII(ClO4)2 afforded a 8-coordinate Fe(II) compound, [FeII(L2)2](ClO4)2 (3); however its reaction with hydrated CoII(ClO4)2 resulted in 6-coordinate [CoII(L2)2](ClO4)2. It is interesting to observe field-induced slow magnetic relaxation in the 7-coordinate Co(II) compound 2 and 8-coordinate Fe(II) compound 3, which further supports the validity of designing high coordination number compounds as single-molecule magnets. Direct current magnetic studies demonstrate that 2 has a very large positive D value (56.2 cm−1) and a small E value (0.66 cm−1), indicating easy plane magnetic anisotropy. Consistent with the larger D value, an effective spin-reversal barrier of Ueff = 100 K (71.4 cm−1) is obtained, which is the highest value reported for 7-coordinate Co(II) complexes with a pentagonal bipyramidal geometry. In contrast, 8-coordinate Fe(II) compound 3 exhibits uniaxial magnetic anisotropy.

The compound (2S)-eriodictyol is an important flavonoid that can be derived from (2S)-naringenin through flavonoid 3'-hydroxylase (F3'H) catalyzation. F3'H is a cytochrome P450 enzyme that requires a cytochrome P450 reductase (CPR) to function. However, P450s have limited applications in industrial scale biosynthesis, owing to their low activity. Here, an efficient SmF3'H and a matched SmCPR were identified from Silybum marianum. To improve the efficiency of SmF3'H, we established a high-throughput detection method for (2S)-eriodictyol, in which the promoter combination of SmF3'H and SmCPR were optimized in Saccharomyces cerevisiae. The results revealed that SmF3'H/SmCPR should be expressed by using promoters with similar and strong expression levels. Furthermore, directed evolution was applied to further improve the efficiency of SmF3'H/SmCPR. With the optimized promoter and mutated combinations SmF3'HD285N/SmCPRI453V, the (2S)-eriodictyol titer was improved to 3.3 g/L, the highest titer in currently available reports. These results indicated that S. cerevisiae is an ideal platform for functional expression of flavonoid related P450 enzymes.

Irreversible consumption of sulfur aroused from shuttle reaction is the major challenge for liquid electrolyte lithium–sulfur batteries, although various sulfur-based cathodes have been designed. I...

In this study, papain and alcalase were used to generate antioxidant peptides from yak bone protein. The antioxidant activities of hydrolysates in vitro were evaluated by 2,2′-azinobios-(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging activity, total reducing power, ferrous ion chelating ability and hydroxyl radical scavenging activity. The hydrolysates generated by alcalase possessed the best antioxidant activity among unhydrolyzed protein and samples treated by papain, but the antioxidant activity decreased after simulated gastrointestinal digestion in vitro. The products of simulated gastrointestinal digestion were separated by ultrafiltration and high performance liquid chromatography, and the amino acid sequences of peptides were identified by mass spectrometry. The digestion sites within peptides were predicted by a bioinformatics strategy, and ten peptides were selected for synthesis. Among 10 synthetic peptides, Gly-Phe-Hyp-Gly-Ala-Asp-Gly-Val-Ala, Gly-Gly-Pro-Gln-Gly-Pro-Arg and Gly-Ser-Gln-Gly-Ser-Gln-Gly-Pro-Ala possessed strong antioxidant activities, among which Gly-Phe-Hyp-Gly-Ala-Asp-Gly-Val-Ala had a significant cytoprotective effect in Caco-2 cells under oxidative stress induced by H2O2, which reduced the formation of reactive oxygen species and malondialdehyde, and improved the activity of antioxidant enzymes in cells. These results showed that yak bone peptides exhibited strong antioxidant activity and have a potential value as a new type of natural antioxidant.

The thermally induced cyclodehydrofluorization of iron tetrakis(pentafluorophenyl)porphyrin proceeded highly stereoselectively to give a prochiral product on a gold surface in an ultrahigh vacuum, whereas dehydrocyclization of the respective iron tetrakisphenylporphyrin did not show such selectivity. Stereoselectivity was predominantly observed for closely packed layers, which is an indication of intermolecular cooperativity and steric constraints induced by adjacent species. Density functional theory identified intermolecular packing constraints as the origin of such selectivity during the reaction. Scanning tunneling microscopy revealed the formation of an enantiomerically pure two-dimensional self-assembly as a conglomerate of mirror domains. On-surface two-dimensional topochemistry, as reported herein, may open new routes for stereoselective synthesis.

Gas sensors with high response, low operating temperature and superior selectivity are highly desired for monitoring toxic gases in the environment. Herein, a formaldehyde (HCHO) gas sensor with outstanding sensing properties is proposed based on Cu-doped Sn3O4 hierarchical nanoflowers that are synthesized via a facile hydrothermal method. The Cu-doped Sn3O4 gas sensors exhibit conspicuously improved sensing performance to HCHO compared with the pure Sn3O4 gas sensor at a relatively low operating temperature of 160°C. Specifically, the gas sensor based on the 4 wt% Cu-doped Sn3O4 composite exhibits a high response up to 53 toward 100 ppm HCHO, a fast response time of 5 s, and low detection limit of 1 ppm. In addition, the prepared Cu-doped Sn3O4 gas sensor possesses conspicuous advantages comprising a good selectivity, perfect reproducibility and excellent long-time stability. The sensing mechanism of the proposed gas sensor is explained by the electron depletion theory, and the possible reasons for the improvement of sensing properties by Cu doping are also discussed. It’s strongly believed that the Cu-doped Sn3O4 sensor has a practical application in HCHO detection.

This study investigates the strength progression of calcium aluminate cement (CAC)-bonded castables with a CAC content ranging from 2 to 16 wt% in the temperatures between 300 and 1000 °C. Focusing on the phase changes and microstructure evolution of the hydrates due to heating, we discovered that castables with higher CAC contents have increased strengths between 300 and 800 °C because the morphology and structure of the dehydrated C3AH6 and AH3 remain similar. At 1000 °C, a higher strength of the 16 wt% CAC castable results from the higher degree of coalescence/sintering between the particles formed from the decomposition products of CAC hydrates. The CAC-bonded castables were prepared using tabular alumina aggregates and α-Al2O3 micro-powder as starting materials, and CAC as the binder. The phase compositions and the microstructures of the castable matrices were characterised by X-ray powder diffraction and scanning electron microscopy, respectively.

Bacillus cereus is an opportunistic pathogen that can cause emetic or diarrheal foodborne illness. Previous studies have identified multiple pathogenic B. cereus strains and characterized a variety of virulence factors. Here, we demonstrate that the virulence and lethality of B. cereus for mammalian cells and host animals involve the interaction of B. cereus flagellin proteins and the host-cell-surface-localized glycosphingolipid Gb3 (CD77, Galα1-4Galβ1-4Glcβ1-Cer). We initially found that B. cereus infection was less lethal for Gb3-deficiencient A4galt−/- mice than for wild-type mice. Subsequent experiments established that some factor other than secreted toxins must account of the observed differential lethality: Gb3-deficiencient A4galt−/- mice were equally susceptible to secreted-virulence-factor-mediated death as WT mice, and we observed no differences in the bacterial loads of spleens or livers of mice treated with B. cereus strain vs. mice infected with a mutant variant of incapable of producing many secreted toxins. A screen for host-interacting B. cereus cell wall components identified the well-known flagellin protein, and both flagellin knockout strain assays and Gb3 inhibitor studies confirmed that flagellin does interact with Gb3 in a manner that affects B. cereus infection of host cells. Finally, we show that treatment with polyclonal antibody against flagellin can protect mice against B. cereus infection. Thus, beyond demonstrating a previously unappreciated interaction between a bacterial motor protein and a mammalian cell wall glycosphingolipid, our study will provide useful information for the development of therapies to treat infection of B. cereus.

Porous carbon materials doped with atomically dispersed metal sites (ADMSs) are promising electrocatalysts for oxygen reduction reaction (ORR) electrocatalysis. In this work, we fabricated hierarchical porous nitrogen-doped carbon nanofibers with atomically dispersed Fe-N4 sites by carbonization of electrospinning iron-based metal-organic frameworks (MOFs)/polyacrylonitrile nanofibers for ORR electrocatalysis. Remarkably, the resultant carbon nanofibers with atomically dispersed Fe-N4 sites exhibit extraordinary electrochemical performance with an onset potential of 0.994 V and a halfwave potential of 0.876 V in alkaline electrolyte, comparable to the benchmark commercial Pt/C catalyst. The high catalytic performance is originated from the unique hierarchically porous 1D carbon structure and abundant highly active atomically dispersed Fe-N4 sites.

We investigate a family of dinuclear dysprosium metallocene single-molecule magnets (SMMs) bridged by methyl and halogen groups [Cp'2 Dy(μ-X)]2 (Cp'=cyclopentadienyltrimethylsilane anion; 1: X=CH3- ; 2: X=Cl- ; 3: X=Br- ; 4: X=I- ). For the first time, the magnetic easy axes of dysprosium metallocene SMMs are experimentally determined, confirming that the orientation of them are perpendicular to the equatorial plane which is made up of dysprosium and bridging atoms. The orientation of the magnetic easy axis for 1 deviates from the normal direction (by 10.3°) due to the stronger equatorial interactions between DyIII and methyl groups. Moreover, its magnetic axes show a temperature-dependent shifting, which is caused by the competition between exchange interactions and Zeeman interactions. Studies of fluorescence and specific heat as well as ab initio calculations reveal the significant influences of the bridging ligands on their low-lying exchange-based energy levels and, consequently, low-temperature magnetic properties.

Pathway optimization plays an important role in fine-tuning metabolic pathways. In most conditions, more than three genes are involved in the biosynthesis pathway of a specific target product. To improve the titer of products, rational regulation of a group of genes by a series of promoters with different strengths is essential. On the basis of a series of RNA-Seq data, a set of 66 native promoters was chosen to fine-tune gene expression in Saccharomyces cerevisiae. Promoter strength was characterized by measuring the fluorescence strength of the enhanced green fluorescent protein through fluorescence-activated cell sorting. The expressions of PTDH1, PPGK1, PINO1, PSED1, and PCCW12 were stronger than that of PTDH3, whereas those of another 15 promoters were stronger than that of PTEF1. Then, 30 promoters were chosen to optimize the biosynthesis pathway of (2S)-naringenin from p-coumaric acid. With a high-throughput screening method, the highest titer of (2S)-naringenin in a 5 L bioreactor reached 1.21 g/L from p-coumaric acid, which is the highest titer according to the currently available reports.

Iron and steel industry emission is an important industrial source of air pollution. However, little is known about the relationship between volatile organic compounds (VOCs) emitted and regional air pollution. In this study, VOCs emissions from a typical iron and steel plant in Yangtze River Delta (YRD, China) were monitored from April 2018 to March 2019. The ozone formation potential (OFP) and secondary organic aerosol (SOA) formation of VOCs were calculated to reveal the influence of VOCs emissions on regional ozone and particulate pollution, and the sensitivity analysis approach was performed to explore the qualitative and quantitative relationships between VOCs and O3, as well as VOCs and PM2.5. The VOCs concentration was 93.76 ± 266.97 ppbv during the study. The OFP was 760.08 ± 2391.90 μg m−3, and aromatics were the predominant precursors, contributing 54.05% of the total OFP. Furthermore, the SOA estimated by fractional aerosol coefficient (FAC) and time-resolved (TR) methods were 6.032 ± 13.347 μg m−3 and 0.971 ± 4.650 μg m−3, accounting for 8.65–26.39% (13.78 ± 7.46%) and 1.55–4.20% (2.22 ± 1.23%) of the PM2.5 concentrations, respectively. The results indicated that VOCs were more sensitive to O3 pollution in high pollution domains, whereas VOCs were more sensitive to PM2.5 pollution in low pollution domains. We concluded that reducing VOCs emissions might be effective in alleviating photochemical pollution episodes in areas around iron and steel industry, and the haze pollution occurred in these regions may be caused by the primary emission of PM, and the contribution of SOA was relatively small.

Oxidative stress is one of the hallmarks of ischemic stroke. Catalase-based (CAT) biomimetic complexes are emerging as promising therapeutic candidates that are expected to act as neuroprotectants for ischemic stroke by decreasing the damaging effects from H2O2. Unfortunately, these molecules result in the unwanted production of the harmful hydroxyl radical, HO•. Here, we report a series of salen-based tri-manganese (Mn(III)) metallocryptands (1-3) that function as catalase biomimetics. These cage-like molecules contain a unique "active site" with three Mn centers in close proximity, an arrangement designed to facilitate metal cooperativity for the effective dismutation of H2O2 with minimal HO• production. In fact, significantly greater oxygen production is seen for 1-3 as compared to the monomeric Mn(Salen) complex, 1c. The most promising system, 1, was studied in further detail and found to confer a greater therapeutic benefit both in vitro and in vivo than the monomeric control system, 1c, as evident from inter alia studies involving a rat model of ischemic stroke damage and supporting histological analyses. We thus believe that metallocryptand 1 and its analogues represent a new and seemingly promising strategy for treating oxidative stress related disorders.

Among the three key active components (KACs) of Magnolia officinalis bark extract (ME), 4-O-methylhonokiol and honokiol showed higher antiproliferation activities than magnolol in the oral squamous cancer cell lines (Cal-27, SCC-9, and SCC-4). Oral bioavailabilities of ME-KACs were poor (

Raw material from biomass and green preparation processes are the two key features for the development of green products. As a bio-lubricant in metalworking fluids, estolides of ricinoleic acid are considered as the promising substitute to mineral oil with a favorable viscosity and viscosity index. Thus, an efficient and sustainable synthesis protocol is urgently needed to make the product really green. In this work, an environment-friendly Brønsted acidic ionic liquid (IL) 1-butanesulfonic acid diazabicyclo[5.4.0]undec-7-ene dihydrogen phosphate ([HSO3-BDBU]H2PO4) was developed as the efficient catalyst for the production of oligomeric ricinoleic acid from ricinoleic acid under solvent-free conditions. The reaction parameters containing reaction temperature, vacuum degree, amount of catalyst and reaction time were optimized and it was found that the reaction under the conditions of 190 °C and 50 kPa with 15 wt % of the [HSO3-BDBU]H2PO4 related to ricinoleic acid can afford a qualified product with an acid value of 51 mg KOH/g (which corresponds to the oligomerization degree of 4) after 6 h. Furthermore, the acid value of the product can be adjusted by regulating the reaction time, implying this protocol can serve as a versatile method to prepare the products with different oligomerization degree and different applications. The other merit of this protocol is the facile product separation by stratification and decantation ascribed to the immiscibility of the product and catalyst at room temperature. It is also worth mentioning that the IL catalyst can be used at least for five cycles with high catalytic activity. As a result, the protocol based on the IL catalyst, i.e. [HSO3-BDBU]H2PO4 shows great potential in industrial production of oligomeric ricinoleic acid from ricinoleic acid.

The electron spin characters of paramagnetic endohedral metallofullerenes (EMFs) are sensitive to their surroundings, which offer an opportunity to manipulate their paramagnetic properties. Here we reported the amination of paramagnetic Gd@C82 and revealed that morpholine groups can be used as a tool to fine-tune properties of Gd@C82. Changes of their paramagnetic properties have been observed under different temperatures and among three derivatives. Addition of morpholine groups eliminates the single unpaired electron on the carbon cage, and causes lower symmetry of the carbon cage and location limit of encapsulated gadolinium, leading serious restriction of Gd@C82 and gadolinium motion. The high sensitivity of spin population to chemical modification offers us the possibility to investigate the spin qubit property and further realize quantum control on a molecular level.

Cyclic (alkyl)(amino)carbenes (cAACs) are the merely known ligand set being capable of stabilizing two-coordinate cobalt(0) complexes. While two complexes of the type [(R2-cAAC)2Co] [R2-cAAC = 5,5-...

As a prominent alternative to toxic dyes/pigments, nanostructural color pixels have garnered tremendous attention in applications related to display/imaging devices and color printings. However, current color pixels mostly offer static color responses. In relation to this, dynamic color tuning properties must be investigated in order to expand their functionalities and promote their use in the fields of encryption and anti-counterfeiting. In this study, a simple array of hydrogenated amorphous silicon nanogratings is proposed to realize polarization-encrypted full-color images via the coupling of incident light into different leaky mode resonances within the nanogratings. The proposed pixels can readily switch from vivid full colors to indistinguishable orange color by altering the incident polarization state. Hence, unlike the reported polarization-tuned color generation schemes that merely allow for the color variation of the image or require complicated designs to hide the color information, the proposed approach can encrypt arbitrary full-color images via a simple tuning of the incident polarization state. Owing to the localized leaky mode resonances supported by the nanogratings, the pixel can still implement the polarization-encrypted functionality even when it contains only four gratings, thus enabling a remarkably high resolution. The proposed simple scheme may provide a credible new pathway for accelerating the practical applications of high-resolution encryption and anti-counterfeiting.

A novel three-dimensional porous dysprosium coordination polymer {[Dy2L2(bpdo)2(H2O)(CH3OH)]·2ClO4·2CH3CN}n (1) has been successfully assembled by combining a superparamagnetic building block of [DyLCl(CH3OH)]2 with the organic ligand 4,4′-bipyridine-N,N′-dioxide (bpdo) (H2L = N′-(2-hydroxybenzylidene)picolinohydrazide). Interestingly, upon the release and/or absorption of different solvent molecules, 1 undergoes reversible single-crystal-to-single-crystal (SCSC) transitions, resulting in the formation of another layer compound of {[DyL(bpdo)(H2O)]·ClO4·2H2O}n (2). This structural transformation involves the breaking and reforming of coordination bonds and leads to significant changes in the relaxation behaviour expected for these coordination polymers, as evidenced by the increase in effective energy barriers from 133 K (1) to 264 K (2) and the slowdown of quantum tunnelling at low temperature. The theoretical calculations indicate that the distinct relaxation behaviours arise mainly from the variation in the coordination geometry around the dysprosium ions. Our work shows that guest molecules can reversibly induce remarkable structural changes in a porous dysprosium coordination polymer and significantly affect its dynamic properties.

There have been reports on the strength decrease of CAC-bonded corundum-based castables without silica fume due to dehydration and decomposition of CAC hydrates when temperature is raised from 110 °C to 900 °C. It is found in this work that there are two steps of strength decrease of the CAC-bonded castables at temperatures of 300 °C and 700 °C respectively. In this paper, corundum-based refractory castables were prepared using tabular alumina and α-Al2O3 micro-powder as starting materials and calcium aluminate cement (CAC) as binder. The phase composition and microstructure of the castable matrix after heating at temperature between 110 °C and 1200 °C were studied by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The strength decreases of the castables at temperatures of 300 °C and, in particular, 700 °C is illustrated using the phase and microstructure evolution of CAC-bonded castable matrixes after heating treatment at different temperatures. For the first time, investigated are the strength increase of the CAC-bonded castables and its causes at temperatures between 900 °C and 1000 °C with emphasis on the structure evolution of the hydrates examined by SEM using high magnification.

The core–shell structure of endohedral fullerene-based anisotropic magnetic molecules of high spin with long coherence time could help scale up quantum systems. In this research, by amination of Gd@C82 with morpholine, three derivatives are functionalized with 5, 7 and 9 morpholine groups providing an interesting model to investigate the relationship between the quantum coherence and the spin environment. The original radical located on the carbon cage is successfully quenched, affording a quantum phase memory times (TM) over 5 μs at 5 K. By increasing the number of substitution groups, spin–lattice relaxation times (T1) also show significant enhancement due to the interaction variation between the molecules and the environments. We found that the TM of the three molecules show no obvious difference below 10 K, while they are limited by T1 at higher temperatures. In this work, the variable functional groups are able to tune both T1 and TM, offering the possibility for application of high-spin magnetic molecules in the field of quantum information processing.

Polyurethane (PU) based phase change materials (PCMs) undergo the solid–solid phase transition and offer state-of-the-art thermal energy storage (TES). Nevertheless, the exploration of these PCMs in real-life applicable smart devices is generally hindered by the technical bottleneck of structural rigidity, low thermal storage capacity and lack of functionalities. Herein, for the first time, we systematically tuned the thermal storage capacity and flexibility of PU-based PCMs (PU-PCMs) by controlling the molecular weight of polyethylene glycol and figured out the optimum selection through the tradeoff between flexibility and thermal storage capacity. We further incorporated functionalized carbon nanotubes (CNTs) in flexible PU-PCMs to improve the thermal conductivity and solar-driven thermal conversion and storage capability. The results demonstrate that the thermal conductivity of the PU–CNT composite is improved by 2.3 times with only 5% weight content of CNTs, and the solar-thermal energy storage efficiency reaches 85.89% at 125 mW cm−2 of irradiation power. Benefitting from the unique mechanical and thermal properties, we further explored our developed composite PCM for solar-driven thermal management of human body parts.

Al2O3–MgAl2O4 castables are prepared using tabular alumina, fused spinel, α-Al2O3 micro-powder, calcium aluminate cement and nano-Al2O3 particles as starting materials. The effects of trace nano-Al2O3 particles (0.2–0.8 wt%) on the thermal shock resistance (TSR) and microstructure of Al2O3–MgAl2O4 castable are investigated. The results show that trace addition of nano-Al2O3 particles contributes to CA6 crystal development and microstructure optimisation. The platelet CA6 crystals form an interlocking network structure creating a toughening effect, which leads to a significant improvement in TSR. In addition, CA6 formation accompanied by volumetric expansion generates many microcracks, which are beneficial for relieving thermal stress during the thermal shock process and enhancing the TSR of the Al2O3–MgAl2O4 castable.

Transition-metal-based phosphides (TMPs) have been considered as attractive electrocatalysts for water splitting due to their earth-abundance and remarkable catalytic activity. As a representative type of precursors, metal-organic frameworks (MOFs) provide ideal plateaus for the design of nanostructured TMPs. In this work, the hierarchically structured iron phosphide nanobundles (FeP-500) were fabricated by one-step phosphorization of an iron-based MOF (MET(Fe)) precursor. The derived FeP-500 nanobundles were constructed by quasi-paralleled one-dimensional nanorods with uneven surface, which provided channels for electrolyte penetration, mass transport, and effective exposure of active sites during the water-splitting process. With the addition of conductive Super P, the obtained FeP-500-S exhibited a good electrocatalytic performance towards the hydrogen evolution reaction in alkaline electrolyte (1 mol L-1 KOH). Furthermore, to investigate the influence of secondary metal doping, a series of isoreticular MOF precursors and bimetallic TMPs were fabricated. The results indicated that the catalytic performance is structure dominated.

Dipeptidyl peptidase IV (DPP-IV) inhibitors have become a new choice to treat diabetes. Here, we studied the DPP-IV inhibitory activity of protein hydrolysates from common carp (Cyprinus carpio) roe. The molecular weight distribution and simulated gastrointestinal digestive stability of hydrolysates produced by four enzymes were analyzed. Papain-generated hydrolysate showed the highest DPP-IV inhibition and effective gastrointestinal stability. New effective peptide sequences from papain hydrolysates were identified using liquid chromatography-tandem mass spectrometry. The bioactivity of IPNVAVD, which was identified from papain hydrolysate (IC50 value of 777.35 ± 5.50 μM), was investigated by Caco-2 and HepG2 cell models. We found that the DPP-IV inhibition by papain hydrolysate was not attenuated after simulated gastrointestinal digestion. In addition, IPNVAVD significantly inhibited the DPP-IV secreted by Caco-2 cells with no cytotoxicity. It also promoted glucose uptake in insulin-resistant HepG2 cells. Transport experiments showed that IPNVAVD could be absorbed intactly by the Caco-2 cell monolayer. Protein hydrolysates from common carp roe inhibited DPP-IV effectively, and they may have potential as functional ingredients in food for diabetic patients.

(2S)-Naringenin, a (2S)-flavanone, is widely used in the food, chemical, and pharmaceutical industries because of its diverse physiological activities. The production of (2S)-naringenin in microorganisms provides an ideal source that reduces the cost of the flavonoid. To achieve efficient production of (2S)-naringenin in Saccharomyces cerevisiae (S. cerevisiae), we constructed a biosynthetic pathway from p-coumaric acid, a cost-effective and more efficient precursor. The (2S)-naringenin synthesis pathway genes were integrated into the yeast genome to obtain a (2S)-naringenin production strain. After gene dosage experiments, the genes negatively regulating the shikimate pathway and inefficient chalcone synthase activity were verified as factors limiting (2S)-naringenin biosynthesis. With fed-batch process optimization of the engineered strain, the titer of (2S)-naringenin reached 648.63 mg/L from 2.5 g/L p-coumaric acid. Our results indicate that the constitutive production of (2S)-naringenin from p-coumaric acid in S. cerevisiae is highly promising.

Patients with stage II or III colorectal cancer (CRC) exhibit various clinical outcomes after radical treatments. The 5-year survival rate was between 50 and 87%. However, the underlying mechanisms of the variation remain unclear. Here we show that AMPKα1 is overexpressed in CRC patient specimens and the high expression is correlated with poor patient survival. We further reveal a previously unrecognized function of AMPKα1, which maintains high level of reduced glutathione to keep reduction–oxidation reaction (redox) homeostasis under stress conditions, thus promoting CRC cell survival under metabolic stress in vitro and enhancing tumorigenesis in vivo. Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity. Suppression of AMPKα1 by using nano-sized polymeric vector induces a favorable therapeutic effect, especially when in combination with oxaliplatin. Our study uncovers a novel function of AMPKα1 in redox regulation and identifies a promising therapeutic strategy for treatment of CRC.

A sandwiched foam concrete (FC) layer with good bond and thermal properties is crucial to the overall performance of a prefabricated insulation panel. In this study, the effects of grade an...

Fusarium species exhibit significant intrinsic resistance to most antifungal agents and fungicides, resulting in high mortality rates among immunocompromised patients. Consequently, a thorough characterization of the antifungal resistance mechanism is required for effective treatments and for preventing fungal infections and reducing antifungal resistance. In this study, an isolate of Fusarium oxysporum (wild-type) with broadly resistant to commonly antifungal agents was used to generate 1,450 T-DNA random insertion mutants via Agrobacterium tumefaciens-mediated transformation. Antifungal susceptibility test results revealed one mutant with increased sensitivity to azoles. Compared with the resistant wild-type, the mutant exhibited low MICs to KTZ, ITC, VRC, POS, and PCZ (0.125, 1, 0.06, 0.5, and 0.125μg/ml, respectively). The T-DNA insertion site of this mutant was characterized as involving two adjacent genes, one encoding a hypothetical protein with unknown function and the other encoding the NADPH-cytochrome P450 reductase, referred as CPR1. To confirm the involvement of these genes in the altered azole susceptibility, the independent deletion mutants were generated and the Cpr1 deletion mutant displayed the same phenotypes as the T-DNA random mutant. The deletion of Cpr1 significantly decreased ergosterol levels. Additionally, the expression of the downstream Cyp51 gene was affected, which likely contributed to the observed increased susceptibility to azoles. These findings verified the association between Cpr1 and azole susceptibility in F. oxysporum. Furthermore, this gene may be targeted to improve antifungal treatments.

Lead halide perovskites always emerge complex interactions among different elemental ions, which lead to multiple intrinsic imperfections. Elemental defects, such as amine, Pb, and I vacancies at A-, B-, and X-sites, are main issues to deteriorate perovskite solar cells (PSCs). Unfortunately, most previous passivators can only temporarily fix partial inactive vacancies as sacrificial agents. Herein, we propose a recovery agent - ferrocene (Fc), which can form a one-dimensional perovskite with adequate steric cavities and suitable dissociation energy to recover all elemental defects back to active light-harvesting perovskites, and regenerate Fc itself meanwhile. Based on this perpetual chain-reaction cycle, corresponding PSCs maintain >10,000-hour lifetime in inert condition and >1,000-hour durabilities under various extreme environments, including continuous 85oC heating, 50% relative humidity wetting, and 1-sun light soaking.

Rhophilin Rho GTPase binding protein 2 (P76RBE) belongs to rhophilin family of Rho-GTPase-binding proteins and is found to contribute to the development of diverse cancers. Data in Oncomine and Kaplan-Meier Plotter databases showed that P76RBE was upregulated in ovarian cancer tissues compared with normal tissues, and patients with high P76RBE expression had worse overall survival, which indicated P76RBE may be associated with the pathogenesis of ovarian cancer. This study aimed to investigate the role of P76RBE in ovarian cancer and to reveal the possible underlying mechanisms. The results demonstrated that P76RBE was highly expressed in ovarian cancer tissues and ovarian cancer cell lines. Functionally, silencing of P76RBE suppressed the proliferation, induced cell cycle arrest, and inhibited migration and invasion in OVCAR-3 and OV-90 cells, while overexpression of P76RBE showed opposite effects on A2780 cells. Mechanically, P76RBE silencing resulted in downregulation of integrin β1, accompanying the reduced NF-κB p65 phosphorylation and nuclear translocation. Importantly, integrin β1 knockdown effectively rescued the effects of P76RBE overexpression on ovarian cancer cells with suppressed proliferation, migration, and invasion. Additionally, in the xenograft tumors derived from OVCAR-3 and OV-90 cell lines, P76RBE knockdown inhibited tumor growth. Meanwhile, the expression of integrin β1 and NF-κB p65 phosphorylation was decreased. In summary, our findings indicate that P76RBE contributes to the progression of ovarian cancer through regulating the integrin β1/NF-κB signaling, and it may be a promising target for ovarian cancer therapy.

Liquorice is a traditional medicine. Triterpenoids such as glycyrrhizin and glycyrrhetinic acid are the main active constituents of liquorice. Studies have revealed that these compounds exert inhibitory effects on several viruses, including SARS-CoV-2. The main mechanisms of action of these compounds include inhibition of virus replication, direct inactivation of viruses, inhibition of inflammation mediated by HMGB1/TLR4, inhibition of β-chemokines, reduction in the binding of HMGB1 to DNA to weaken the activity of viruses, and inhibition of reactive oxygen species formation. We herein review the research progress on the antiviral effects of glycyrrhizin and its derivatives. In addition, we emphasise the significance of exploring unknown antiviral mechanisms, structural modifications, and drug combinations in future studies.

This study aimed to investigate the effect of myofiber changes and protein oxidation on water holding capacity (WHC) of bighead carp fillets stored at −20 °C. WHC, microstructure, protein oxidation parameters, and specific modifications of oxidized amino acids were analyzed during 9 months of frozen storage. Results indicated that WHC decreased accompanied by myofibers’ structural changes (including the formation of cavities among myofibers, breakage of myofibrils and myofibers, and shortening of sarcomeres) and protein oxidation. SDS-PAGE and carbonyl and sulfhydryl content determination of myofibrillar proteins and exudates gave a detailed description of the protein oxidation. LC-MS/MS analysis demonstrated that oxidation, di-oxidation, and 4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA) adduction were the top four oxidative modifications of proteins. Oxidative modifications impaired configuration and polarity of proteins, which may further affect WHC. This study provides plausible explanations to support the role of protein oxidation in the decrease of WHC in frozen fillets.

We demonstrate that the hierarchically porous metal hydroxide/metal–organic framework composite nanoarchitectures exhibit broad-spectrum removal activity for three chemically distinct toxic gases, viz. acid gases, base gases, and nitrogen oxides. A facile and general in-situ hydrolysis strategy combined with gentle ambient pressure drying (APD) was utilized to integrate both Zr(OH)4 and Ti(OH)4 with the amino-functionalized MOF-808 xerogel (G808-NH2). The M(OH)4/G808-NH2 xerogel composites manifested 3D crystalline porous networks and substantially hierarchical porosity, with controllable amounts of amorphous M(OH)4 nanoparticles residing at the edge of xerogel particles. Microbreakthrough tests were performed under both dry and moist conditions to evaluate the filtration capabilities of the composites against three representative compounds: SO2, NH3, and NO2. Compared with the pristine G808-NH2 xerogel, the incorporation of M(OH)4 effectively enhanced the broad-spectrum toxic chemical mitigation ability of the material, with the highest SO2, NH3, and NO2 breakthrough uptake reaching 74.5, 55.3, and 394.0 mg/g, respectively. Post-breakthrough characterization confirmed the abundant M-OH groups with diverse binding configurations, alongside the unsaturated M (IV) centers on the surface of M(OH)4 provided extra adsorption sites for irreversible toxic chemical capture besides Van der Waals driven physisorption. The ability to achieve high-capacity adsorption and strong retention for multiple contaminants is of great significance for real-world filtration applications.

We investigated the anti-aging effects of velvet antler polypeptide on D-galactose (D-gal)-induced aging mice. D-gal-induced aging mice were established and randomly divided into five groups, the control, model, vitamin E (VE), velvet antler polypeptide low-dose and velvet antler polypeptide high-dose groups. The Morris water maze test was used to evaluate the learning and memory abilities of aging mice. Hippocampal neurons were observed via hematoxylin-eosin staining and transmission electron microscopy. Biochemical methods were used to detect the activities of superoxide dismutase, malonaldehyde and other enzymes and evaluate the influence of velvet antler polypeptide on the antioxidant capacity of aging mice. Using 16S rRNA gene sequencing and meristem technology, we assessed the effect of velvet antler polypeptide on aging mice’s intestinal flora and fatty acid metabolism. The experimental results showed that velvet antler polypeptide could significantly improve aging mice’s learning and cognitive abilities, increase the activities of superoxide dismutase, glutathione peroxidase, and catalase in the serum decrease the malonaldehyde content. Intestinal microecological analysis showed that velvet antler polypeptide could significantly increase the beneficial bacterial genus Lactobacillus abundance. Western blot analysis further demonstrated that velvet antler polypeptide could promote fatty acid metabolism by activating peroxisome proliferator-activated receptor α (PPARα) and upregulating the expression of the downstream enzymes carnitine-palmitoyl transferase-1 A and acyl-CoA oxidase 1 while downregulating that of apolipoprotein E4 (APOE4), thereby reducing fatty acid accumulation and increasing adenosine-triphosphate (ATP) production. Therefore, velvet antler polypeptide improves the intestinal microecology and activates the PPARα/APOE4 pathway to regulate fatty acid metabolism.

While assembling superparamagnetic units in a controlled manner is crucial for future applications of molecular nanomagnets, optimizing their magnetic properties while achieving directional assembly of these units still remains a formidable challenge. Herein, we demonstrate how the assembly of two dysprosium chain complexes, namely, [Dy2(L)2Cl2(CH3OH)3]n·nCH3OH (1) and [Dy(L)Cl(DMF)]n (2) (H2L = N‘-(5-bromo-2-hydroxybenzylidene)pyrazine-N-oxide-carbohydrazide), can be successfully manipulated using an appropriate bridging ligand design. Both complexes contain similar dimeric units bridged by two alkoxido oxygens from an L2− ligand, but extended by its pyrazine-N-oxide group exhibiting two distinct coordination modes, namely, single and double pyrazine-N-oxide bridges, respectively. Magnetic studies reveal that both complexes display typical slow magnetic relaxation under zero direct-current field; however, the anisotropy barrier and the coercive field at 2 K for complex 2 are twice as much as that of 1. A further theoretical study indicates that switching the coordination mode from a single pyrazine-N-oxide bridge to double bridges can enhance both the magnetic anisotropy of dysprosium ions and magnetic coupling within the dimeric cores. The synergistic effect between the magnetic anisotropy of dysprosium ions and magnetic interactions among them directly contributes to the overall better performance of complex 2.