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Photo-generated radicals play an important role in photocatalytic reactions, yet numerous radicals undergo self-quenching before contact with the substrate because of their ultrafast lifetimes and limited diffusion distances, which decreases the utilization of free radicals and reduces the activity of photocatalysts. Herein, both hierarchical pores and oxygen vacancies (OVs) were successfully introduced into a titanium-based metal-organic framework (MOF), namely MIL-125-NH2 (MIL for Materials of Institut Lavoisier), via a simple and controllable acid etching method. The generation of OVs increased the yield of photogenerated radicals, while the hierarchical pore structure conferred a pore enrichment effect, thus enhancing the utilization of photogenerated radicals. Owing to the synergistic effect of the hierarchical pores and OVs, the obtained single-crystal nanoreactor, H-MIL-125-NH2-VO, showed much higher catalytic activity for rhodamine (RhB) degradation than pristine MIL-125-NH2. In fact, the rate constant for catalytic RhB degradation in H-MIL-125-NH2-VO was approximately eight times that of MIL-125-NH2. This work highlights the significant contribution of both hierarchical pores and OVs to enhancing the photocatalytic performance of MOFs.

Objectives Our study aims to investigate whether PI3K/mTOR dual inhibitor LY3023414 has synergistic effects with carboplatin in suppressing endometrial cancer (EC), and explore the mechanisms and toxicity of combined therapy. Methods The effects of combined therapy of LY3023414 and carboplatin on cell viability, long-term survival and cell apoptosis were studied in vitro, and on subcutaneous xenograft model of HEC-1A cells and patient derived xenograft (PDX) models with different PI3K pathway mutational patterns in vivo. The synergistic mechanisms were explored on ATM/Chk2 and PI3K signaling pathway. The toxicity of combined therapy was also observed. Results Combined treatment of LY3023414 and carboplatin synergistically inhibited proliferation, colony formation, promoted apoptosis of EC cells, and significantly activated ATM/Chk2 signaling pathway. LY3023414 had synergistic anti-tumor effects with carboplatin in HEC-1A subcutaneous xenograft which harbors PIK3CA mutation. The sensitivity to LY3023414 and carboplatin differed in PDX of EC cases with different mutational patterns of PI3K pathway, and combined therapy exhibited distinct synergistic anti-tumor effects in those harboring different PI3K pathway mutations. No increased drug toxicity in nude mice was seen in combined groups. Conclusions Combined therapy of PI3K/mTOR dual inhibitor LY3023414 and carboplatin had synergistic anti-tumor effects in EC cell line and some of the PDX EC models, without increasing the toxicity of single drug. Enhanced carboplatin-induced DNA damage response (DDR) and cell apoptosis may be the mechanisms of synergistic effects. The anti-tumor effects may correlate with the mutational pattern of PI3K pathway, which provides experimental basis of individual treatments of ECs in the future.

A facile copper-catalyzed aminosulfonylation of O-homoallyl benzimidates with sodium sulfinates in the presence of tert-butyl peroxybenzoate (TBPB) and XPhos ligand has been developed. By using this protocol, a variety of potentially bioactive 1,3-oxazines were directly synthesized. This method has the merits of a cheap catalyst, easily available and stable sulfone reagents, and simple operation.

Aim. The aim of this study was to explore whether letrozole and high-fat diets (HFD) can induce obese insulin-resistant polycystic ovary syndrome (PCOS) with intestinal flora dysbiosis in a rat model. We compared the changes in the intestinal flora of letrozole-induced rats fed with HFD or normal chow, to explore the effects of HFD and letrozole independently and synergistically on the intestinal flora. Methods. Five-week-old female Sprague Dawley (SD) rats were divided into four groups: control (C) group fed with regular diet; L1 group administered with letrozole and fed with regular diet; L2 group received letrozole and fed with HFD; and HFD group fed with HFD. At the end of the experiment, ovarian morphology, hormones, metabolism, oxidative stress, and inflammatory status of all rats were studied. 16S rDNA high-throughput sequencing was used to profile microbial communities, and various multivariate analysis approaches were used to quantitate microbial composition, abundance, and diversity. Results. Compared to the C group, the increased plasma fasting insulin and glucose, HOMA-IR, triglyceride, testosterone, and malondialdehyde were significantly higher in the L2 group, while high-density lipoprotein cholesterol was significantly lower in the L1 group and L2 group. The indices of Chao1 and the Abundance-based Coverage Estimator (ACE) (α-diversity) in the L2 and HFD groups were significantly lower than that in the C group. Bray–Curtis dissimilarity based principal coordinate analysis (PCoA) plots and analysis of similarities (ANOSIM) test showed obvious separations between the L2 group and C group, between the HFD group and C group, and between the L2 and HFD groups. At the phylum level, Firmicutes and ratio of Firmicutes and Bacteroidetes (F/B ratio) were increased in the L2 group; Bacteroidetes was decreased in the L2 and HFD groups. No significant differences in bacterial abundance between the C group and L1 group were observed at the phylum level. Based on linear discriminant analysis (LDA) effect size (LEfSe) analysis, the bacterial genera (the relative abundance > 0.1%, LDA > 3, p < 0.05 ) were selected as candidate bacterial signatures. They showed that the abundance of Vibrio was significantly increased in the L1 group; Bacteroides and Phascolarctobacterium were enriched in the HFD group, and Bacteroides, Phascolarctobacterium, Blautia, Parabacteroides, Akkermansia [Ruminococcus]_torques_group, and Anaerotruncus were enriched in the L2 group. Conclusion. The effect of letrozole on intestinal flora was not significant as HFD. HFD could destroy the balance of intestinal flora and aggravate the intestinal flora dysbiosis in PCOS. Letrozole-induced rats fed with HFD have many characteristics like human PCOS, including some metabolic disorders and intestinal flora dysbiosis. The dysbiosis was characterized by an increased Firmicutes/Bacteroidetes ratio, an expansion of Firmicutes, a contraction of Bacteroidetes, and the decreased microbial richness. Beta-diversity also showed significant differences in intestinal microflora, compared with control rats.

Lieb lattice, a two-dimensional edge-centered square lattice, has attracted considerable interest due to its exotic electronic and topological properties. Although various optical and photonic Lieb lattices have been experimentally demonstrated, it remains challenging for an electronic Lieb lattice to be realized in real material systems. Here, based on first-principles calculations and tight-binding modeling, a silver sulfide (Ag2S) monolayer is reported as a long-sought-after inorganic electronic Lieb lattice. This Lieb-lattice Ag2S is further found to be ultrasoft, which enables its electronic properties and topological states near the Fermi level to be finely tuned, as evidenced by the strain-induced topologically non-trivial edge states near the valence band edge. These results not only provide an ideal platform to further explore and harvest interesting quantum properties but also pave a way to pursue other inorganic electronic Lieb lattices in a broader material domain.

In this paper, a novel sandwich immunosensor based on a toluidine blue (Tb) loaded metal organic framework (Cu(II)-HKUST-1/Tb) as the signal element and a nitrogen-doped 3D carbon nanostructure as the electrode substrate was constructed for the detection of C-reactive protein (CRP). Tb as an electrochemically active agent usually forms a polymer by aggregation in the solvent, causing a poor electrochemical response. Therefore, in order to overcome this obstacle, Cu(II)-HKUST-1 with a porous nanostructure and large specific surface area as a carrier could adsorb a large number of Tb molecules on its surface to improve its electrochemical performance. In addition, the high electron transfer efficiency of the N-doped bamboo-like carbon nanotubes (CoFe/N-GCT) improves the sensitivity of the biosensor. Differential pulse voltammetry (DPV) was used to detect the current signal of Tb at −0.2 V. The current response increased with the increase in concentration of CRP, ranging from 0.5 to 200 ng mL−1. The detection limit is 166.7 pg mL−1 (S/N = 3). Moreover, the proposed biosensor can be applied in real serum sample detection. It has potential applications in the field of biomedicine assays.

The π-conjugation of molecules has a large influence on their excited state properties, especially for red thermally activated delayed fluorescence (TADF) materials. Two orange-red TADF compounds comprising dual dicyano-substituted pyrazine/quinoxaline acceptors have been designed and synthesized. TPA-2DCNQ (3,3'-((phenylazanediyl)bis(4,1-phenylene))bis(2-phenylquinoxaline-6,7-dicarbonitrile) with extended π-conjugated quinoxaline as the acceptor exhibits higher photoluminescence quantum yields (ca. 0.67-0.71) in doped films. A smaller energy splitting (ΔEst ) between the first singlet excited state and triplet excited state is also achieved, indicating that extending the π-conjugation of the acceptor rationally is an effective approach to designing highly efficient long-wavelength TADF materials. Devices with TPA-2DCNQ as the emitter display maximum external quantum efficiencies (EQEs) of 12.6-14.0 %, which are more than twice those of devices containing TPA-2DCNPZ (6,6'-((phenylazanediyl)bis(4,1-phenylene))bis(5-phenylpyrazine-2,3-dicarbonitrile).

Development of new chemistry to simultaneously meet the demands for topology, connectivity, and functionality is highly desired in the research area of covalent organic frameworks (COFs). We explore herein the isocyanide chemistry so as to establish a facile paradigm to integrate functionality and ultrastability in COFs. Using the representative Groebke-Blackburn-Bienaymé (GBB) reaction based on isocyanide chemistry, we are able to construct a series of pyrimidazole-based COFs in one step from isocyanide, aminopyridine, and aldehyde monomers. Diversified functionalities have been bottom-up integrated by the simple replacement of readily available 2-aminopyridine monomers. Meanwhile, the ubiquitous formation of fused imidazole rings within the frameworks has guaranteed their ultrastability. In view of the rich synthetic possibilities provided by isocyanide chemistry, we expect that this contribution opens up a new avenue toward the divergent construction of robust COFs for practical applications.

Gd3+-based contrast agents have been extensively used for signal enhancement of T1-weighted magnetic resonance imaging (MRI) due to the large magnetic moment and long electron spin relaxation time of the paramagnetic Gd3+ ion. The key requisites for the development of Gd3+-based contrast agents are their relaxivities and stabilities which can be achieved by chemical modifications. These modifications include coordinating Gd3+ with a chelator such as diethylenetriamine pentaacetic acid (DTPA) or 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), encapsulating Gd3+ in nanoparticles, conjugation to biomacromolecules such as polymer micelles and liposomes, or non-covalent binding to plasma proteins. In order to have a coherent diagnostic and therapeutic approach and to understand diseases better, the combination of MRI and optical imaging (OI) techniques into one technique entity has been developed to overcome the conventional boundaries of either imaging modality used alone through bringing the excellent spatial resolution of MRI and high sensitivity of OI into full play. Novel MRI and OI bimodal probes have been extensively studied in this regard. This review is an attempt to shed some light on the bimodal imaging probes by summarizing all recent noteworthy publications involving Gd3+ containing MR-optical imaging probes. The several key elements such as novel synthetic strategy, high sensitivity, biocompatibility, and targeting of the probes are highlighted in the review. STATEMENT OF SIGNIFICANCE: The present article aims at giving an overview of the existing bimodal MRI and OI imaging probes. The review structured as a series of examples of paramagnetic Gd3+ ions, either as ions in the crystalline structure of inorganic materials or chelates for contrast enhancement in MRI, while they are used as optical imaging probes in different modes. The comprehensive review focusing on the synthetic strategies, characterizations and properties of these bimodal imaging probes will be helpful in a way to prepare related work.

Little is known about the physiological and molecular mechanisms underlying magnesium (Mg)-deficiency-induced enlargement, cracking and lignification of midribs and main lateral veins of Citrus leaves. Citrus sinensis (L.) Osbeck seedlings were irrigated with nutrient solution at a concentration of 0 (Mg-deficiency) or 2 (Mg-sufficiency) mM Mg(NO3)2 for 16 weeks. Enlargement, cracking and lignification of veins occurred only in lower leaves, but not in upper leaves. Total soluble sugars (glucose + fructose + sucrose), starch and cellulose concentrations were less in Mg-deficiency veins of lower leaves (MDVLL) than those in Mg-sufficiency veins of lower leaves (MSVLL), but lignin concentration was higher in MDVLL than that in MSVLL. However, all four parameters were similar between Mg-deficiency veins of upper leaves (MDVUL) and Mg-sufficiency veins of upper leaves (MSVUL). Using label-free, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, we identified 1229 and 492 differentially abundant proteins (DAPs) in MDVLL vs MSVLL and MDVUL vs MSVUL, respectively. Magnesium-deficiency-induced alterations of Mg, nonstructural carbohydrates, cell wall components, and protein profiles were greater in veins of lower leaves than those in veins of upper leaves. The increased concentration of lignin in MDVLL vs MSVLL might be caused by the following factors: (i) repression of cellulose and starch accumulation promoted lignin biosynthesis; (ii) abundances of proteins involved in phenylpropanoid biosynthesis pathway, hormone biosynthesis and glutathione metabolism were increased; and (iii) the abundances of the other DAPs [viz., copper/zinc-superoxide dismutase, ascorbate oxidase (AO) and ABC transporters] involved in lignin biosynthesis were elevated. Also, the abundances of several proteins involved in cell wall metabolism (viz., expansins, Rho GTPase-activating protein gacA, AO, monocopper oxidase-like protein and xyloglucan endotransglucosylase/hydrolase) were increased in MDVLL vs MSVLL, which might be responsible for the enlargement and cracking of leaf veins.

Integration of two or more biomolecules with synergetic and complementary effects on a material surface can help to obtain multi-functions for various biomedical applications. However, the amounts of biomolecules integrated and their physiological functions are compromised due to the limited surface anchoring sites. Herein, we propose a novel concept of film engineering strategy “from surface to bulk synergetic modification”. This new concept is realized by employing the surface amine groups of plasma polymerized allylamine (PPAm) film for grafting a molecule e.g., thrombin inhibitor, bivalirudin (BVLD), meanwhile its bulk amine groups is used as a universal depot for storing and releasing therapeutic nitric oxide (NO) gas as supplement to the functions of BVLD. It is demonstrated that such a “from surface to bulk synergetic modification” film engineering can impart the modified-substrates with anti-platelet and anti-coagulant dual functions, giving rise to a highly endothelium-mimetic thromboresistant property. We believe that our research provides a very promising strategy to deliver multifunctional surface versatilely that require NO release in combination with other properties, which will find broad biomedical applications in blood-contacting devices, and et al. Moreover, it also provides a brand-new film engineering strategy for tailoring surface multi-functionalities of a wide range of materials., Graphical abstract Image 1, Highlights • A concept of “from surface to bulk synergetic modification” is proposed for tailoring surface multi-functionalities. • The surface amine groups of plasma polymerized allylamine (PPAm) film were used for grafting bivalirudin. • The bulk amine groups of PPAm film is utilized as the universal depots for storing and releasing nitric oxide.

The combination therapy of cisplatin (CDDP) and metformin (MET) is a clinical strategy to enhance therapeutic outcomes in lung cancer. However, the efficacy of this combination is limited due to the asynchronous pharmacokinetic behavior of CDDP and MET, used as free drugs. Therefore, in this work, hyaluronic acid-cisplatin/polystyrene-polymetformin (HA-CDDP/PMet) dual-prodrug co-assembled nanoparticles were developed, with precise ratiometric co-delivery of CDDP and MET for chemo-immunotherapy against lung cancer. The HA-CDDP/PMet NPs showed a spherical morphology with an average particle size of 166.5 nm and a zeta potential of -17.4 mV at an HA-CDDP and PMet mass ratio of 1/1. The content of CDDP and MET in HA-CDDP/PMet NPs was 3.7% and 15.2%, respectively. In vitro antitumor effects of CDDP and MET resulted in an improved synergistic action on proliferation inhibition and apoptosis induction on Lewis lung cancer cells. Moreover, in vivo by co-delivered HA-CDDP/PMet NPs into tumor cells, with an excellent intracellular CDDP and MET cleavage. These nanoparticles exhibited significantly increased tumor accumulation and tumor growth inhibition and prolonged animal overall survival in Lewis lung cancer bearing mice without nephrotoxicity, excess of free drugs and homo-prodrugs. The synergistic effect of MET and CDDP in HA-CDDP/PMet NPs resulted in up-regulation of the cleaved poly(ADP)-ribose polymerase (PARP) protein to induce tumor cell apoptosis, and down-regulation of the excision repair cross-complementation group 1 (ERCC1) protein level to decrease the resistance to CDDP. The synergistic effect of MET and CDDP in HA-CDDP/PMet NPs also resulted in induction of the adenosine monophosphate (AMP)-activated protein kinase-α (AMPK-α) pathway and inhibition of the mammalian target of rapamycin (mTOR), finally exerting a chemotherapeutic effect and modulating a potent immunotherapeutic function with an increase in CD4+ and CD8+ T cells, a concomitant decrease in regulatory T (Treg) cells, and an increased expression of the cytokines IFN-γ and TNF-α. Therefore, the immunochemotherapy using CDDP and MET mediated by this dual prodrug co-assembled nano-platform might provide a promising treatment strategy against lung cancer.

G-triplex (G3) structures formed with three consecutive G-tracts have recently been identified as a new emerging guanine-rich DNA fold. There could likely be a wide range of biological functions for G3s as occurring for G-quadruplex (G4) structures formed with four consecutive G-tracts. However, in comparison to the many reports on G4 nanoassemblies that organize monomers together in a controllable manner, G3-favored nanoassemblies have yet to be explored. In this work, we found that a natural alkaloid of sanguinarine can serve as a dynamic ligand glue to reversibly switch the dimeric nanoassemblies of the thrombin binding aptamer G3 (TBA-G3). The glue planarity was considered to be a crucial factor for realizing this switching. More importantly, external stimuli including pH, sulfite, O2 and H2 O2 can be employed as common regulators to easily modulate the glue's adhesivity for constructing and destructing the G3 nanoassemblies as a result of the ligand converting between isoforms. However, this assembly behavior does not occur with the counterpart TBA-G4. Our work demonstrates that higher-order G3 nanoassemblies can be reversibly operated by manipulating ligand adhesivity. This provides an alternative understanding of the unique behavior of guanine-rich sequences and focuses attention on the G3 fold since the nanoassembly event investigated herein might occur in living cells.

Copper (Cu)-toxic effects on Citrus grandis growth and Cu uptake, as well as gene expression and physiological parameters in leaves were investigated. Using RNA-Seq, 715 upregulated and 573 downregulated genes were identified in leaves of C. grandis seedlings exposed to Cu-toxicity (LCGSEC). Cu-toxicity altered the expression of 52 genes related to cell wall metabolism, thus impairing cell wall metabolism and lowering leaf growth. Cu-toxicity downregulated the expression of photosynthetic electron transport-related genes, thus reducing CO2 assimilation. Some genes involved in thermal energy dissipation, photorespiration, reactive oxygen species scavenging and cell redox homeostasis and some antioxidants (reduced glutathione, phytochelatins, metallothioneins, l-tryptophan and total phenolics) were upregulated in LCGSEC, but they could not protect LCGSEC from oxidative damage. Several adaptive responses might occur in LCGSEC. LCGSEC displayed both enhanced capacities to maintain homeostasis of Cu via reducing Cu uptake by leaves and preventing release of vacuolar Cu into the cytoplasm, and to improve internal detoxification of Cu by accumulating Cu chelators (lignin, reduced glutathione, phytochelatins, metallothioneins, l-tryptophan and total phenolics). The capacities to maintain both energy homeostasis and Ca homeostasis might be upregulated in LCGSEC. Cu-toxicity increased abscisates (auxins) level, thus stimulating stomatal closure and lowering water loss (enhancing water use efficiency and photosynthesis).

The biomimetic synthesis of guaianolide dimers lavandiolides H, I, and K and artematrolide F containing a spirolactone moiety has been accomplished for the first time from naturally abundant arglabin in four to six steps with an overall yield up to 60%, and a series of natural product-like guaianolide dimers, trimer, and tetramer were also successfully synthesized. Notably, the trimeric compound exhibited antihepatoma cytotoxicity more potent than that of sorafenib with IC50 values of 6.2 μM (HepG2), 6.8 μM (Huh7), and 7.2 μM (SK-HEP-1).

Limited data are available on the physiological responses of Citrus to nitrogen (N) deficiency. ‘Xuegan’ (Citrus sinensis (L.) Osbeck) and ‘Shantian pummelo’ (Citrus grandis (L.) Osbeck) seedlings were fertilized with nutrient solution at a N concentration of 0, 5, 10, 15 or 20 mM for 10 weeks. N deficiency decreased N uptake and N concentration in leaves, stems and roots and disturbed nutrient balance and homeostasis in plants, thus inhibiting plant growth, as well as reducing photosynthetic pigment levels and impairing thylakoid structure and photosynthetic electron transport chain (PETC) in leaves, hence lowering CO2 assimilation. The imbalance of nutrients intensified N deficiency’s adverse impacts on biomass, PETC, CO2 assimilation and biosynthesis of photosynthetic pigments. Citrus displayed adaptive responses to N deficiency, including (a) elevating the distributions of N and other elements in roots, as well as root dry weight (DW)/shoot DW ratio and root-surface-per-unit volume and (b) improving photosynthetic N use efficiency (PNUE). In general, N deficiency had less impact on biomass and photosynthetic pigment levels in C. grandis than in C. sinensis seedlings, demonstrating that the tolerance of C. grandis seedlings to N deficiency was slightly higher than that of C. sinensis seedlings, which might be related to the higher PNUE of the former.

Citrate has a prominent role as a substrate in cellular energy metabolism. Recently, citrate has been shown to drive inflammation. However, the role of citrate in lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains unclear. Here, we aimed to clarify whether extracellular citrate aggravated the LPS-induced ALI and the potential mechanism. Our findings demonstrated that extracellular citrate aggravated the pathological lung injury induced by LPS in mice, characterized by up-regulation of pro-inflammatory factors and over-activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in the lungs. In vitro, we found that citrate treatment significantly augmented the expression of NLRP3 and pro-IL-1β and enhanced the translocation of NF-κB/p65 into the nucleus. Furthermore, extracellular citrate plus adenosine-triphosphate (ATP) significantly increased the production of reactive oxygen species (ROS) in primary murine macrophages. Inhibiting the production of ROS with a ROS scavenger N-acetyl-L-cysteine (NAC) attenuated the activation of NLRP3 inflammasome. Altogether, we conclude that extracellular citrate may serve as a damage-associated molecular pattern (DAMP) and aggravates LPS-induced ALI by activating the NLRP3 inflammasome.

An ultrasensitive electrochemical sensor has been constructed for the detection of single nucleotide polymorphisms (SNPs) based on DNA-functionalized Cd-MOFs-74 as cascade signal amplification probe under enzyme-free conditions. Interestingly, the introduction of an auxiliary probe did not disturb the detection of SNP targets, but could bind more Cd-MOFs-74 signal elements to enhance the different pulse voltammetry electrochemical signal 2~3 times as compared to sensing system without auxiliary probe, which obviously improves the sensitivity of the proposed sensor. Experimental results taking p53 tumor suppressor gene as SNP model demonstrated that the proposed method can be employed to sensitively and selectively detect target p53 gene fragment with a linear response ranging from 0.01 to 30 pmol/L (detection limit of 6.3 fmol/L) under enzyme-free conditions. Utilizing this strategy, the ultrasensitive SNP electrochemical sensor is a promising tool for the determination of SNPs in biomedicine. Graphical Abstract.

Trinucleotide repeats (TRs) with abnormal lengths and atypical folding are implicated in various neurodegenerative diseases. The least stable cytosine-cytosine (C–C) mismatches in TRs when structuring into homoduplexes/hairpins have more chance in certain sequence contexts to preferentially adopt an extrahelical (E-motif) conformation with respect to those in polarity-inverted intrahelical counterparts. Herein, we designed a trihydroxyphenyl porphyrin ligand (POH3) to meet the challenge towards resolving the E-motif conformation. POH3 exhibited a specific 2:1 binding with DNAs adopting the E-motif cytosine conformation, independent of the TRs length. The trihydroxyl pattern was very crucial to gain the E-motif selectivity over the polarity-inverted counterparts via the complementary hydrogen bonding that occurred in the minor groove. Our work first elucidates the rationale in designing ligands to selectively resolve the E-motif nucleotides within TRs.

Trihydroxyphenyl porphyrin (POH3) was designed to specifically bind with a triplex DNA resulting in a turn-on fluorescence response. This ensemble can be developed into a catalytic triplex DNAzyme towards porphyrin metalation. The catalytic activity is initiated by the enhanced basicity of POH3 upon binding with the triplex DNA.

Background: Currently, the association between sodium-glucose cotransporter 2 inhibitor (SGLT-2i) and malignancy risk has yet to be fully elucidated. This meta-analysis aimed to determine the relationship between SGLT-2i and malignancy risk in type 2 diabetes (T2D) patients.Methods: We searched PubMed, ScienceDirect, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science to identify randomized controlled trials (RCTs) published up to August 2020 related to T2D patients treated with SGLT-2i vs. placebo or other hypoglycemic agents. The meta-analysis's primary outcome was malignancies' incidence, and the results were evaluated using risk ratio (RR) and 95% confidence interval (CI).Results: We reviewed 76 articles (77 RCTs), comprising 45,162 and 43,811 patients in SGLT-2i and control groups, respectively. Compared with the control group, SGLT-2i had no significant association with augmented overall malignancy risk in T2D patients (RR = 1.05, 95% CI = 0.97–1.14, P = 0.20), but ertugliflozin may upsurge the risk (RR = 1.80, 95% CI = 1.02–3.17, P = 0.04). Compared with active hypoglycemic agents, dapagliflozin may increase (RR = 2.71, 95% CI = 1.46–6.43, P = 0.02) and empagliflozin may decrease (RR = 0.67, 95% CI = 0.45–0.98, P = 0.04) the malignancy risk. Compared with placebo, empagliflozin may exhibit risk increase (RR = 1.25, 95% CI = 1.05–1.49, P = 0.01), primarily in digestive system (RR = 1.48, 95% CI = 0.99–2.21, P = 0.05).Conclusions: Our results proposed that in diverse comparisons, ertugliflozin and dapagliflozin seemed to increase the malignancy risk in T2D patients. Empagliflozin may cause malignancy risk reduction compared with active hypoglycemic agents but increase overall risk primarily in the digestive system compared with placebo. In short, the relationship between SGLT-2i and malignancy in T2D patients remains unclear.

Background Limited data are available on the responses of reactive oxygen species (ROS) and methylglyoxal (MG) metabolisms to low pH in roots and leaves. In China, quite a few of Citrus are cultivated in acidic soils (pH Citrus sinensis) and ‘Sour pummelo’ (Citrus grandis) (C. sinensis were more tolerant to low pH than C. grandis) seedlings were irrigated daily with nutrient solution at a pH of 2.5, 3 or 5 for nine months. Thereafter, we examined low pH effects on growth, and superoxide anion production rate (SAP), malondialdehyde (MDA), MG, antioxidants, and enzymes related to ROS and MG detoxification in roots and leaves in order to (a) test the hypothesis that low pH affected ROS and MG metabolisms more in roots than those of leaves, and (b) understand the roles of ROS and MG metabolisms in Citrus low pH-tolerance and -toxicity. Results Compared with control, most of the physiological parameters related to ROS and MG metabolisms were greatly altered at pH 2.5, but almost unaffected at pH 3. In addition to decreased root growth, many fibrous roots became rotten and died at pH 2.5. pH 2.5-induced changes in SAP, the levels of MDA, MG and antioxidants, and the activities of most enzymes related to ROS and MG metabolisms were greater in roots than those of leaves. Impairment of root ascorbate metabolism was the most serious, especially in C. grandis roots. pH 2.5-induced increases in MDA and MG levels in roots and leaves, decreases in the ratios of ascorbate/(ascorbate+dehydroascorbate) in roots and leaves and of reduced glutathione/(reduced+oxidized glutathione) in roots were greater in C. grandis than those in C. sinensis. Conclusions Low pH affected MG and ROS metabolisms more in roots than those in leaves. The most seriously impaired ascorbate metabolism in roots was suggested to play a role in low pH-induced root death and growth inhibition. Low pH-treated C. sinensis roots and leaves had higher capacity to maintain a balance between ROS and MG production and their removal via detoxification systems than low pH-treated C. grandis ones, thus contribute to the higher acid-tolerance of C. sinensis.

Galectin-13 (Gal-13) plays numerous roles in regulating the relationship between maternal and fetal tissues. Low expression levels or mutations of the lectin can result in pre-eclampsia. The previous crystal structure and gel filtration data show that Gal-13 dimerizes via formation of two disulfide bonds formed by Cys136 and Cys138. In the present study, we mutated them to serine (C136S, C138S and C136S/C138S), crystalized the variants and solved their crystal structures. All variants crystallized as monomers. In the C136S structure, Cys138 formed a disulfide bond with Cys19, indicating that Cys19 is important for regulation of reversible disulfide bond formation in this lectin. Hemagglutination assays demonstrated that all variants are inactive at inducing erythrocyte agglutination, even though gel filtration profiles indicate that C136S and C138S could still form dimers, suggesting that these dimers do not exhibit the same activity as wild-type (WT) Gal-13. In HeLa cells, the three variants were found to be distributed the same as with WT Gal-13. However, a Gal-13 variant (delT221) truncated at T221 could not be transported into the nucleus, possibly explaining why women having this variant get pre-eclampsia. Considering the normally high concentration of glutathione in cells, WT Gal-13 should exist mostly as a monomer in cytoplasm, consistent with the monomeric variant C136S/C138S, which has a similar ability to interact with HOXA1 as WT Gal-13.

Vegetable production is recognized as an important anthropogenic source of nitrous oxide (N2O) emission. An improved understanding of yield-scaled N2O emission from vegetable production can promote innovation for climate smart cropping. In this study, we performed a meta-analysis to quantify yield-scaled N2O emission from six types of vegetable crops, to elucidate the effects of greenhouse cultivation and different types of nitrogen (N) fertilizers on yield-scaled N2O emission from vegetable crops. Significant differences were observed in N2O emission factor (EF) and area- and yield-scaled N2O emissions among the six vegetable types. Stem and seed vegetables showed the lowest and highest area- and yield-scaled N2O emissions, respectively. The average yield of all of the vegetables was significantly higher in greenhouses than in open fields. However, only leafy vegetables were observed to have significantly lower yield-scaled N2O in greenhouses than in open fields. Emissions of yield-scaled N2O in response to inorganic N application rate differed among the different vegetable types. The replacement of inorganic N fertilizer with manure significantly reduced yield-scaled N2O emission from leafy vegetables, but significantly enhanced that from fruit vegetables. Enhanced-efficiency N fertilizer (EENF) significantly increased yield, and significantly reduced area- and yield-scaled N2O emissions from all of the vegetable types; however, it was less effective for root vegetables and open field cultivation.

Catalytic reduction of 4-nitrophenol (4-NP) represents a useful method of converting 4-NP into a more environmentally friendly product, 4-aminophenol (4-AP). Prussian blue (PB) (Fe3[Fe(CN)6]2) and its Prussian blue Analogues (PBAs) (MII[Fe(CN)6] PBAs (MII = Mn, Co, Ni, and Zn) exhibit hierarchical porous structures, and electrochemical characteristics, making PBAs promising catalysts for 4-NP reduction. Nevertheless, very few literatures report the reduction of 4-NP to 4-AP employing PBAs, and no studies have been ever conducted to evaluate the effects of different MII species of [Fe(CN)6]-based PBAs on the catalytic conversion of 4-NP to 4-AP. Herein, we examine the catalytic reductive performance of various MII[Fe(CN)6] PBAs (MII = Co, Fe, Mn, Ni, and Zn), in the presence of sodium borohydride (NaBH4), on 4-NP reduction to 4-AP. The catalytic activity of PBAs for 4-NP reduction was in the order CoFeCN > NiFeCN > FeFeCN > MnFeCN > ZnFeCN. The corresponding activation energies are determined as 32, 43, 46, 47, and 54 kJ/mol for CoFeCN, NiFeCN, MnFeCN, FeFeCN and ZnFeCN, respectively. Especially, CoFeCN shows the highest catalytic activity with a rate constant of 0.457 min−1 and a calculated turnover frequency of 6.3 × 10−3 s−1, which are higher than many reported noble metal catalysts because of its high surface area and catalytic activities towards hydrogen generation and hydrogenation. CoFeCN (and NiFeCN) also exhibit excellent reusabilities even after 6 consecutive reduction experiments. These findings demonstrate that PBAs, such as CoFeCN and NiFeCN, are highly advantageous catalysts for reduction of 4-NP and would be promising for reducing other nitro-aromatic compounds.

While sulfate radical (SO4-)-based processes are useful to degrade acetaminophen (ACE), studies of using peroxymonosulfate (PMS) to degrade ACE are quite limited. In addition, although Co is validated as the most effective metal for activating PMS, very few Co catalysts have been developed and investigated for activating PMS to degrade ACE. Since carbon is a promising substrate to support Co nanoparticles (NPs) to form Co/carbon composite catalysts, most existing carbon substrates require delicate fabrications. As biochar is an easy-to-obtain but versatile carbon material, pyrolysis of Co/lignin affords an advantageous Co-impregnated biochar (CoIB) as an attractive catalyst for PMS activation. Specifically, as CO2 substitutes N2 as a reaction medium for pyrolysis of Co/lignin, the syngas production from pyrolysis can be substantially improved and a magnetic CoIB is afforded. This CoIB consists of evenly-distributed Co nanoparticles (NPs) impregnated in carbon matrices of biochar, and possesses several superior characteristics, such as high porosity, large surface area and magnetism, enabling CoIB a promising catalyst for activating PMS to degrade ACE. CoIB also shows a much higher catalytic activity of PMS activation than CoIBN2, and Co3O4 for degrading ACE. CoIB is also recyclable for activating PMS to effectively degrade ACE for multiple cycles. The ACE degradation pathway by this CoIB-activated PMS is proposed according to the degradation products. These findings validate that CoIB is assuredly an advantageous heterogeneous catalyst, which can be easily prepared from pyrolysis of Co/lignin in CO2 with concomitant enhanced syngas production for effectively activating PMS to degrade ACE.

OBJECTIVE This study was conducted to investigate the effects of in ovo feeding (IOF) of creatine pyruvate (CrPyr) on the energy metabolism in thigh muscle of embryos and neonatal broilers. METHODS A total of 960 eggs were randomly assigned to three treatments: i) non-injected control group, ii) saline group injected with 0.6 mL of physiological saline (0.75%), and iii) CrPyr group injected with 0.6 mL of physiologi-cal saline (0.75%) containing 12 mg CrPyr/egg on 17.5 d of incubation. After hatching, 120 male chicks (close to the average body weight of the pooled group) in each group were randomly assigned to eight replications. The feeding experiment lasted 7 days. RESULTS The results showed that IOF of CrPyr increased glucose concentrations in the thigh muscle of broilers on 2 d after injection (p

While zirconium (Zr)-based metal organic frameworks (MOFs) are promising for conversion of levulinic acid (LA) to γ-valerolactone (GVL) through catalytic transform hydrogenation (CTH), these reported Zr MOFs for LA conversion must be synthesized in toxic dimethylformamide (DMF). From the viewpoint of sustainability, it is preferable to avoid usage of DMF-based solvents to prepare these Zr MOFs. As water is a green solvent, the aim of this study is to develop and investigate Zr MOFs, which are prepared in water, for LA conversion to GVL. Specifically, monocarboxylic acids (e.g., formic acid, acetic acid and propanoic acid) are employed as modulators during the preparation of water-born ZrF. The role of modulators is extremely important for the well-developed formation of water-born ZrF. In addition, different monocarboxylic acid modulators also significantly influence the morphology of water-born ZrF; nevertheless, their crystalline structures and acidities are equivalent. As for LA conversion, these water-born modulated ZrF MOFs are validated to successfully convert LA to GVL. Especially, the formic acid-modulated ZrF can exhibit LA conversion = 96%, selectivity for GVL = 98% and yield of GVL = 98%. These water-born modulated ZrF also exhibit even higher catalytic activities than the typical DMF-based ZrF and reported Zr-based MOFs in LA conversion to GVL. These water-born ZrF could be also reused even without regeneration for multiple cyclic LA conversion. These results and findings prove that the water-born ZrF is not only environmentally benign but also more effective for LA conversion to GVL.

Intracellular doxorubicin (DOX) pumping out of cells through the P-glycoprotein (P-gp) transporter leads to the reduction of intracellular DOX levels and induces multidrug resistance (MDR). A hyaluronic acid-deoxycholic acid-histidine and Pluronic F127 (PF127) mixed micellar system, named HA-DOCA-His-PF micelles, functionalized with active targeted endocytosis mediated via CD44 receptor, intracellular triggered DOX release under endosome-pH, and combined with PF127-mediated P-gp efflux inhibition was developed for sufficient intracellular DOX delivery and MDR reversion. The DOX/HA-DOCA-His-PF drug-loaded micelles displayed endosomal pH-mediated self-assembly/disassembly characteristics, triggered DOX release under an endosomal (pH 5.5) environment, and demonstrated enhanced cytotoxicity and superior MDR reversion performance against drug-resistant MCF-7/Adr tumor cells. Importantly, superior antitumor activity of DOX/HA-DOCA-His-PF micelles was presented on the growth inhibition of MCF-7/Adr tumor cells, by further inhibiting the P-gp activity on intracellular DOX efflux through the depletion of intracellular adenosine triphosphate content. This multifunctional micellar system could be facilitated by the intracellular DOX delivery for reversing MDR of breast cancer.

Cobalt nanoparticles (NPs) immobilized on N-doped carbonaceous substrates are attractive heterogeneous catalysts for activating Oxone to degrade pollutants. However, conventional preparation of Co NPs/N-doped carbon composites involves multi-step syntheses of N-doped carbon substrates, and then immobilization of Co NPs on substrates, which are complicated and time-consuming. In this study, a convenient one-step fabrication technique is developed for preparing a composite of Co/N-doped carbon via carbonization of a mixture of melamine and cobalt acetate. The resulting Co@CN is comprised of Co NPs evenly distributed over a carbon nitride (CN) matrix. Co@CN could exhibit porous structures and magnetic controllability, making it an appealing catalyst for Oxone activation. Catalytic activities for Oxone activation by Co@CN are investigated via batch-type decolorization experiments of amaranth (AMR) dye. Co@CN shows much higher catalytic activities than C3N4 and Co3O4, the benchmark catalyst, for Oxone activation to decolorize AMR. In comparison to the other reported catalysts, Co@CN demonstrates the much lower activation energy for AMR decolorization. The mechanism of AMR decolorization by Co@CN-activated Oxone is also determined by investigating Electron paramagnetic resonance (EPR) analysis and effects of radical inhibitors on AMR decolorization. These comparisons indicate the promising features of Co@CN as a heterogeneous catalyst for activating Oxone. The fabrication technique proposed here can be also adopted to develop similar composites of metallic NPs distributed over CN matrices for various catalytic applications.

The three-dimensional forming property of the hernia repair mesh is very important in the application. In order to study the correlation between process parameters and formability property, three variables are set for the test: diameter of raw materials, structure and drawing-off density. Results show that within a certain range, the forming performance of the patch becomes better with the increasing of the diameter of raw materials, and comparing with the double-comb opening through structure, the forming properties of the double-comb velveteen structure are better. Besides, in the same conditions, the forming property is better with the draw-off density increases.

The sensitive and rapid quantification of lysozymes (Lys) is a critical goal in clinical practice. Herein, a novel, label-free and sensitive turn ON–OFF chemiluminescent (CL) probe for Lys was developed based on modulating the biocatalytic ability of the Cu2−xSe nanoparticles. The synthesized Cu2−xSe nanoparticles could significantly enhance the chemiluminescence signal of the luminol–H2O2 system owing to their high copper deficiency, where a very bright blue CL emission was directly observed by the naked eye in darkness and it could last for a long period of up to 36 minutes. However, Lys could induce the aggregation of the Cu2−xSe nanoparticles due to the electrostatic attraction, which could be monitored by SEM and dark-field imaging. The aggregated Cu2−xSe nanoparticles with lower copper deficiency density could suppress their catalytic ability and turn off the chemiluminescence of luminol–H2O2. The established ON–OFF CL strategy exhibited a selective response to protein Lys and showed a quantitative relationship between the changes in the CL signals and the concentration of Lys over a wide range of 0.5–5000 ng mL−1, with a low detection limit of 0.36 ng mL−1. This study provides a promising strategy for detecting biomolecules by exploiting their specific interactions with nanomaterials.

Multi-stimuli-responsive materials have attracted tremendous attention owing to their promising applications. Herein, we constructed two multifunctional optoelectronic materials (PXZ-DCzBN and PXZ-DtCzBN) composed of benzonitrile, phenoxazine and carbazole or tert-butyl carbazole moieties, which are endowed with thermally activated delayed fluorescence and mechanochromic luminescence characteristics. Intriguingly, under external stimuli, PXZ-DCzBN presents a unique multicolor transformation, including single-molecule white-light emission, while PXZ-DtCzBN simply displays bicolor switching. The white-light emission of PXZ-DCzBN is eventually attributed to the coexistence of two different conformers: ‘quasi-equatorial’ (eq) and ‘quasi-axial’ (ax). PXZeq-DCzBN can convert into PXZax-DCzBNvia recrystallization in poor solvents. PXZeq-DCzBN generates long-wavelength emission from an intramolecular charge transfer excited state, and PXZax-DCzBN emits short-wavelength fluorescence through a locally excited transition. This study evaluates the importance of the conformational isomerization of PXZ moieties and provides an innovative perspective for understanding the relationship between molecular conformations and excited-state characteristics.

Here we first reported that graphitic carbon nitride nanosheet (g-C3N4 NS) could effectively quench the chemiluminescence (CL) of luminol-hydrogen peroxide (H2O2) system. According to the new discovery, a label-free and homogeneous CL aptasensing platform was designed for sensitive detecting of biomarkers. In the absence of target, DNA probe containing hemin/G-quadruplex DNAzyme structure was adsorbed on the surface of g-C3N4 NS, causing the CL quenching of luminol through an electron transfer process. However, in the presence of the target, a DNA-DNA duplex was formed due to DNA hybridization reaction and target recognition effect, which could not be adsorbed onto the g-C3N4 NS surface because of its weak affinity. Thus, the electron transfer was blocked and the CL emission of luminol could be enhanced. The proposed CL aptasensor could detect carcinoembryonic antigen (CEA) with a detection limit of 63.0 pg/mL and it can also be used as a general detecting strategy for adenosinetriphosphate (ATP) detection. This aptasensing platform exhibited high sensitivity toward biomarkers and the probe need not be labeled, showing great promise for disease diagnosis.

Pure organic room-temperature phosphorescence (RTP) materials are considered as potential candidates for replacing precious metal complexes to fabricate highly efficient organic light-emitting devices (OLEDs). However, applications of the reported RTP materials in OLEDs are seriously impeded by their low photoluminescence quantum yields (PLQYs) in a thin film state. To overcome these obstacles, we established a new strategy to construct highly efficient OLEDs based on a pure organic RTP material sensitized fluorescence emitter by selecting benzimidazole-triazine molecules (PIM-TRZ), 2,6-di(phenothiazinyl)naphthalene (β-DPTZN), and 5,6,11,12-tetraphenylnaphthacene (rubrene) as host, phosphor sensitizer, and fluorescent emitter, respectively. The perfect combination of host, phosphorescent sensitizer, and fluorescent emitter in the emitting layer ensure the outstanding performance of the devices with an external quantum efficiency (EQE) of 15.7 %.

Pure organic room temperature phosphorescence (RTP) materials are considered as potential candidates for replacing precious metal-based complexes to fabricate highly efficient organic light emitting devices (OLEDs). However, for reported RTP materials, low photoluminescence quantum yields (PLQYs) in thin film state seriously impede their applications in OLEDs. On the other hand, how using normal organic fluorescence materials to fabricate OLEDs with an internal quantum efficiency (IQE) over 25% remains a great unaddressed issue beyond the thermally activated delayed fluorescence (TADF) sensitization approach. Here, we establish a strategy to construct highly efficient OLEDs based on pure organic RTP material sensitized fluorescence emitter. The key point for our strategy is that benzimidazole-triazine molecules (PIM-TRZ), 2,6-di(phenothiazinyl)naphthalene (β-DPTZN) and 5,6,11,12-tetraphenylnaphthacene (rubrene) were screened as host, phosphor sensitizer and fluorescent emitter, respectively. Detail photophysical characterizations demonstrate that the host material PIMTRZ with unique RTP nature is critical for achieving phosphor sensitizing process. As an organic RTP compound, the singlet and triplet state energy levels of β-DPTZN perfectly match with those of PIMTRZ, resulting in the formation and lasting existence of phosphor’s excitons in emitting layer. The large overlap between the absorption spectrum of rubrene and PL spectrum of PIM-TRZ:10% β-DPTZN film can facilitate the Förster energy transfer from the triplet β-DPTZN to the singlet rubrene and the finally displayed fluorescence is derived from singlet excited states of rubrene. The perfect collocation of host, phosphorescent sensitizer and fluorescent emitter in the emitting layer promise the predominant performance of the devices with external quantum efficiency (EQE) of 15.7%. The PLQY of emitting layer is 60.3%, and therefore about 90% carrier injection induced excitons are harvested for light emission. We present a new strategy to fabricate efficient fluorescent devices by employing ingenious combination of host, phosphorescent sensitizer and fluorescent emitter, which is significant to the development of OLEDs.

Phosphorus (P) is an essential macronutrient for plant growth, development and production. However, little is known about the effects of P deficiency on nutrient absorption, photosynthetic apparatus performance and antioxidant metabolism in citrus. Seedlings of ‘sour pummelo’ (Citrus grandis) were irrigated with a nutrient solution containing 0.2 mM (Control) or 0 mM (P deficiency) KH2PO4 until saturated every other day for 16 weeks. P deficiency significantly decreased the dry weight (DW) of leaves and stems, and increased the root/shoot ratio in C. grandis but did not affect the DW of roots. The decreased DW of leaves and stems might be induced by the decreased chlorophyll (Chl) contents and CO2 assimilation in P deficient seedlings. P deficiency heterogeneously affected the nutrient contents of leaves, stems and roots. The analysis of Chl a fluorescence transients showed that P deficiency impaired electron transport from the donor side of photosystem II (PSII) to the end acceptor side of PSI, which showed a greater impact on the performance of the donor side of PSII than that of the acceptor side of PSII and photosystem I (PSI). P deficiency increased the contents of ascorbate (ASC), H2O2 and malondialdehyde (MDA) as well as the activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR) and glutathione reductase (GR) in leaves. In contrast, P deficiency increased the ASC content, reduced the glutathione (GSH) content and the activities of SOD, CAT, APX and monodehydroascorbate reductase (MDHAR), but did not increase H2O2 production, anthocyanins and MDA content in roots. Taking these results together, we conclude that P deficiency affects nutrient absorption and lowers photosynthetic performance, leading to ROS production, which might be a crucial cause of the inhibited growth of C. grandis.

The complex oxide heterostructures such as LaAlO3/SrTiO3 (LAO/STO) interface are paradigmatic platforms to explore emerging multi-degrees of freedom coupling and the associated exotic phenomena. In this study, we reveal the effects of multiorbital and magnetic ordering on Rashba spin-orbit coupling (SOC) at the LAO/STO (001) interface. Based on first-principles calculations, we show that the Rashba spin splitting near the conduction band edge can be tuned substantially by the interfacial insulator-metal transition due to the multiorbital effect of the lowest t_2g bands. We further unravel a competition between Rashba SOC and intrinsic magnetism, in which the Rashba SOC induced spin polarization is suppressed by the interfacial magnetic ordering. These results deepen our understanding of intricate electronic and magnetic reconstruction at the perovskite oxide interfaces and shed light on the engineering of oxide heterostructures for all-oxides-based spintronic devices., 24 pages, 4 figures

The hydrogen-rich water (HW) has been reported to possess a beneficial role in patients with diabetes. However, a systemic evaluation with an appropriate animal model is necessary to reveal its mechanisms and efficacy. Herein, the protective effects of drinking HW on lipid and glucose metabolism, oxidative stress, and inflammation in type 2 diabetes mellitus (T2DM) rats were investigated. The well-modeled T2DM rats (induced by high-fat diet combined with low-dose streptozotocin (STZ) injection) were divided into two groups (n ≥ 15 of each): fed a high-fat diet and drinking distilled water or HW at a constant concentration above 1.0 ppm; normal rats were used as control group (n ≥ 10): fed a regular diet and drinking distilled water. Several biomarkers of lipid and glucose metabolism, oxidative stress ,and inflammation were evaluated after drinking distilled water or HW for 3 weeks. The effect of HW on liver, kidney, and spleen of T2DM rats was also analyzed by HE and Oil Red O staining. The results showed that drinking HW suppressed the increase in glucose, total cholesterol, oxidative stress, and inflammation. Moreover, HW also ameliorates hyperglycemia-induced liver, kidney, and spleen dysfunction. Overall, this study indicates that patients with T2DM may be able to improve their condition by supplementing HW as daily drinking water.

G-quadruplex DNAs (G4s) have been reported to exhibit the DNAzyme activities by binding with some metal complexes and functional organic ligands. However, there is a challenge to develop metalloenzyme-mimic G4-based innate DNAzymes using the complexed metal ions directly serving as the active centers. This will diversify DNAzymes for developing novel devices since G4 structures are more polymorphic than the other DNA foldings. In this work, we found that the lanthanide trivalent cerium ion of Ce3+ can bind to the human telomere G4 (htG4) according to a 1 : 2 binding mode favorable for creating metalloenzymes-mimic G4 DNAzymes. This Ce3+-G4 entity exhibits a peroxidase activity towards the oxidation of the substrate of 3,3,5,5-tetramethylbenzidine (TMB) by hydrogen peroxide. The 5′ G4 tetrads with the orderly arranged carbonyl oxygen atoms are believed to be the coordination sites for Ce3+ and favor the conversion between Ce3+ and Ce4+. Our work provides an alternative feasibility in developing the G4-based innate DNAzymes for variant applications.

Two-dimensional (2D) alloys represent a versatile platform that extends the properties of atomically thin transition-metal dichalcogenides. Here, using molecular beam epitaxy, we investigate the growth of 2D vanadium-molybdenum diselenide alloys, VxMo1-xSe2, on highly oriented pyrolytic graphite and unveil their structural, chemical, and electronic integrities via measurements by scanning tunneling microscopy/spectroscopy, synchrotron X-ray photoemission, and X-ray absorption spectroscopy (XAS). Essentially, we found a critical value of x = similar to 0.44, below which phase separation occurs and above which a homogeneous metallic phase is favored. Another observation is an effective increase in the density of mirror twin boundaries of constituting MoSe2 in the low V concentration regime (x

In this study, a ratiometric electrochemical sensor based on metal-organic frameworks (MOFs) was developed for sensing of multiplex metal ions. The bifunctional MOFs were prepared in a way to integrate two signal tags and a detection probe. In the presence of target metal ions, the target metal ions can replace the framework metal-ion center in the original MOFs through an ion-exchange reaction, leading to ratiometric electrochemical signals under different applied potentials. One consisted of the Cu

G-triplex (G3) has been recognized as a popular intermediate during the folding of G-quadruplex (G4). This has raised interest to anticipate the ultimate formation of G3 by shortening the G4-forming oligonucleotides with the remaining three G-tracts. Some G3 structures have been validated and their stability has been found to be affected by the loop sequences similar to G4s. In this work, however, we first found that an intermolecular parallel G4 structure was preferred in K+ for the oligonucleotide 5′-TGGGTAGGGCGGG-3′ (DZ3) containing only three G-tracts. We screened auramine O (AO) as the appropriate fluorophore with a molecular rotor feature to target this G4 structure. AO bound with DZ3 in a 1 : 4 ratio, as confirmed by isothermal titration calorimetry experiments, suggesting the formation of a tetramolecular G4 structure (4erG4). The excimer emission from the labelled pyrene and the DNA melting behavior at various pHs in the presence of Ag+ proved the formation of the 4erG4 structure rather than the prevalent intramolecular G3 folding. This work demonstrates that one should be cautious while putatively predicting a G3 structure from an oligonucleotide containing three G-tracts.

In green species, sucrose can help antagonize abiotic stress. Sucrose phosphate synthase (SPS) is a well-known rate-limiting enzyme in the synthesis of sucrose. To date, however, there is no known crystal structure of SPS from plant or cyanobacteria. In this study, we report the first co-crystal structure of SPS from Thermosynechococcus elongatus with UDP and sucrose-6-phosphate (S6P). Within the catalytic site, the side chains of His158 and Glu331, along with two phosphate groups from UDP, form hydrogen bonds with the four hydroxyl groups of the glucose moiety in S6P. This association causes these four hydroxyl groups to become partially negatively charged, thus promoting formation of the C1 oxocarbenium ion. Breakage of the hydrogen bond between His158 and one of the hydroxyl groups may trigger covalent bond formation between the C1 oxocarbenium ion and the C2 hydroxyl of fructose-6-phosphate. Consistent with our structural model, we observed that two SPS mutants, H158A and E331A, lost all catalytic activity. Moreover, electron density of residues from two loops (loop1 and loop2) in the SPS A-domain was not observed, suggest their dynamic nature. B-factor analysis and molecular dynamics stimulations of the full-length enzyme and A-domain indicate that both loops are crucial for binding and release of substrate and product. In addition, temperature gradient analysis shows that SPS exhibits its highest activity at 70°C, suggesting that this enzyme has the potential of being used in industrial production of S6P.

Nitrite (NO2−) is one of the important pollutants in food and the environment, which can seriously endanger the health of human beings. Therefore, detecting nitrite in food, environmental and biological samples is very significant for health monitoring. Herein, polymer carbon dots (PCDs) doped with nitrogen and phosphorus were prepared by polymerization of ascorbic acid (AA) and polyethylenimine (PEI) with phosphoric acid, and exhibited excellent stability, adjustable fluorescence emissions and good biocompatibility. It was found that the PCDs presented a sensitive response to nitrite (NO2−), and they were successfully applied for NO2− analysis in water and milk samples, and the dynamic monitoring of nitrite entry into Hep-2 cells.

An integrated aptamer macroarray functionalized with reduced graphene oxide (rGO) to specifically capture and sensitively detect cancer cells is reported. The capture for cancer cells is based on effective recognition of the modified rGO surface through the aptamer against epithelial cell adhesion molecule (EpCAM). The rough structure of rGO enhances morphologic interactions between rGO film interface and the cancer cells, while super-hydrophilicity of modified rGO hinders nonspecific cell capture. The synergistic interactions offer the aptamer macroarray high efficiency of cancer cell capture. By means of a turn-on fluorescence strategy based on the conformation change of the aptamer induced by the target recognition, the enriched cancer cells can be directly read out at excitation/emission wavelengths of 550/680 nm without washing, separation, and dying steps. The working range is 1 × 102 to 2 × 104 cells per mL with a detection limit of 22 cells per mL. The results indicate that the aptamer macroarray has a considerable foreground for early diagnosis, therapy, and monitoring of cancer.

In this work, we present a versatile surface engineering strategy by the combination of mussel adhesive peptide mimicking and bioorthogonal click chemistry. The main idea reflected in this work derived from a novel mussel-inspired peptide mimic with a bioclickable azide group (i.e., DOPA 4 -azide). Similar to the adhesion mechanism of the mussel foot protein (i.e., covalent/noncovalent comediated surface adhesion), the bioinspired and bioclickable peptide mimic DOPA 4 -azide enables stable binding on a broad range of materials, such as metallic, inorganic, and organic polymer substrates. In addition to the material universality, the azide residues of DOPA 4 -azide are also capable of a specific conjugation of dibenzylcyclooctyne- (DBCO-) modified bioactive ligands through bioorthogonal click reaction in a second step. To demonstrate the applicability of this strategy for diversified biofunctionalization, we bioorthogonally conjugated several typical bioactive molecules with DBCO functionalization on different substrates to fabricate functional surfaces which fulfil essential requirements of biomedically used implants. For instance, antibiofouling, antibacterial, and antithrombogenic properties could be easily applied to the relevant biomaterial surfaces, by grafting antifouling polymer, antibacterial peptide, and NO-generating catalyst, respectively. Overall, the novel surface bioengineering strategy has shown broad applicability for both the types of substrate materials and the expected biofunctionalities. Conceivably, the “clean” molecular modification of bioorthogonal chemistry and the universality of mussel-inspired surface adhesion may synergically provide a versatile surface bioengineering strategy for a wide range of biomedical materials.

Many important fruit trees are commercially planted on acidic soils and are prone to Al toxicity. Significant progress has been made in our understanding of the physiological and molecular responses of fruit trees to Al toxicity during the past decade. In the chapter, Al toxic effects on growth and structure, physiological and biochemical responses of fruit trees to Al toxicity (uptake of mineral nutrients and water, leaf gas exchange and chlorophyll a fluorescence, reactive oxygen species and methylglyoxal detoxification systems, nonstructural carbohydrates, and organic acids), factors affecting Al tolerance of fruit trees (species and cultivars, Al uptake and distribution, secretion of organic acid anions, nitric oxide, methyl jasmonate, and efficient maintenance of redox homeostasis via reactive oxygen species and methylglyoxal detoxification systems), and molecular aspects of Al tolerance in fruit trees are summarized. Also, several aspects needed to be further studied are discussed.

Sensitive detection, especially in situ monitoring of intracellular MMP-2, is extremely desirable for cancer early diagnosis, evaluation of therapy, and discovery of the new anti-cancer drug. Herein, a programmed microcapsule-type MMP-2 responsive nanosensor based on mesoporous silica nanoparticles (MSN) is developed to realize in situ imaging monitoring of intracellular MMP-2. In the wrapping anti-MMP-2 antibody sealed microcapsule-type nanosensor, a black hole fluorescence quencher (BHQ-3) is covalently combined onto the inner walls of the MSN mesopores, and the fluorescein Cy5 is loaded in the cavity of MSN, resulting in fluorescence “OFF” state. With the existence of MMP-2, the anti-MMP-2 antibody which acts as a “bio-lid” could detach from the surface of the nanosensor owing to the binding MMP-2 with the antibody, leading to the release of the fluorescein Cy5 to produce fluorescence “ON” state. The prepared programmed microcapsule-type MMP-2 responsive nanosensor is capable of sensitive in situ imaging monitoring of intracellular MMP-2 and is further verified by tracking the change of intracellular MMP-2 level in response to MMP-2-repressive drugs. Thus, the nanosensor give a platform for in vivo detection of biomarkers for diagnosis, evaluation of therapy, and discovery of the new anti-cancer drug.