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Background: Chronic Myeloid Leukemia (CML) is a myeloproliferative disease caused by BCR-ABL oncoprotein. Tyrosine kinase inhibitors have been developed to inhibit the activity of BCR-ABL; however, drug resistance and side effect occur in clinic application. Therefore, it is urgent to find novel drugs for CML treatment. Under the guidance of cytotoxic activity, crude extracts of 55 fungal strains from the medicinal mangrove Acanthus ilicifolius were evaluated, and one potent cytotoxic natural compound, brefeldin A (BFA), was discovered from Penicillium sp. (HS-N-29). Objective: This study was aimed to determine the cytotoxic activity of BFA and the effect on the activation and expression of BCR-ABL in K562 cells. Method: We evaluated cytotoxic activity by MTT assay and soft agar clone assay; apoptosis and cell cycle distribution by Muse cell analyzer. The protein level of BCR-ABL and signaling molecules was detected by western blotting, and the mRNA level of BCR-ABL was determined by RT-PCR. Results: BFA inhibited cell proliferation, induced G2/M cell cycle arrest, and stimulated cell apoptosis in K562 cells. Importantly, for the first time, we revealed that BFA inhibited the activation of BCR-ABL and consequently inhibited the activation of its downstream signaling molecules in K562 cells. Moreover, we found BFA degraded BCR-ABL without affecting its transcription in K562 cells, and BFA-induced BCR-ABL degradation was related to caspase activation, while not to autophagy or ubiquitinated proteasome degradation pathway. Conclusion: Our present results indicate that BFA acts as a dual functional inhibitor and degrader of BCR-ABL, and BFA is a potential compound for chemotherapeutics to overcome CML.

Electrochemistry and X-ray absorption spectroscopy (XAS) of MnO2/reduced graphene oxide (RGO) were made to evaluate capacitive performance and electronic structure as a supercapacitor. MnO2 was deposited on the surface of RGO by a spontaneous redox reaction. At low current density (1 A g−1), the specific capacitance of MnO2/RGO (MRGO) greatly increased with increasing growth time from 281 to 462 F g−1. Electrochemical results show that the specific capacitance of RGO and MRGO arises from the combined contributions of electrochemical double-layer capacitance (EDLC) and pseudo-capacitance. To gain insights into the charge storage mechanism of RGO and MRGO, it was characterized using ex-situ soft XAS techniques at Mn L-edge and C, O K-edges in the charging/discharging process. The ex-situ soft XAS results provide evidence that the contribution of RGO to specific capacitance involves an oxygen-functionality-related contribution of pseudocapacitance and EDLC. In addition, the specific capacitance of MRGO reveals pseudocapacitive contributions from the redox processes that involve the Mn(III)/Mn(IV) redox reaction in MnO2. This work utilizes electrochemical and ex-situ XAS techniques to elucidate charge storage mechanism for supercapacitor applications.

Carbon nitride-based photocatalysts hold an enormous potential in producing hydrogen. A strategy to simultaneously create isotype heterojunctions and active sites in highly-crystallized carbon nitride is anticipated to significantly boost the photocatalytic activity, but is yet to be realized. Herein, we find that cobalt salt added in the ionothermal synthesis can promote the phase transition of heptazine-based crystalline carbon nitride (CCN) to triazine-based poly(triazine imide) (PTI), rendering the creation of single-atom cobalt coordinated isotype CCN/PTI heterojunction. Co-CCN/PTI exhibits an appreciable apparent quantum yield of 20.88% at 425 nm for photocatalytic hydrogen production with a rate achieving 3538 μmol h−1 g−1 (λ > 420 nm), which is 4.8 times that of CCN and 27.6 times that of PTI. The high photocatalytic activity is attributed to the Type II isotype highly-crystallized CCN/PTI heterojunction for promoting charge carrier migration, and the single-atom Co sites for accelerating surface oxidation reaction.

Purpose We hypothesized that the effect of blood lipid–related metabolites on primary open-angle glaucoma (POAG) would differ according to specific lipoprotein particles and lipid sub-fractions. We investigated the associations of blood levels of lipoprotein particles and lipid sub-fractions with POAG. Design Cross-sectional study. Participants Individuals recruited for the baseline visit of the population-based Singapore Epidemiology of Eye Disease study (n = 8503). Methods All participants underwent detailed standardized ocular and systemic examinations. A total of 130 blood lipid–related metabolites were quantified using a nuclear magnetic resonance metabolomics platform. The analyses were conducted in 2 stages. First, we investigated whether and which lipid-related metabolites were directly associated with POAG using regression analyses followed by Bayesian network modeling. Second, we investigated if any causal relationship exists between the identified lipid-related metabolites, if any, and POAG using 2-sample Mendelian randomization (MR) analysis. We performed genome-wide association studies (GWAS) on high-density lipoprotein (HDL) 3 cholesterol (after inverse normal transformation) and used the top variants associated with HLD3 cholesterol as instrumental variables (IVs) in the MR analysis. Main Outcome Measure Primary open-angle glaucoma. Results Of the participants, 175 (2.1%) had POAG. First, a logistic regression model showed that total HDL3 cholesterol (negatively) and phospholipids in very large HDL (positively) were associated with POAG. Further analyses using a Bayesian network analysis showed that only total HDL3 cholesterol was directly associated with POAG (odds ratio [OR], 0.72 per 1 standard deviation increase in HDL3 cholesterol; 95% confidence interval [CI], 0.61–0.84), independently of age, gender, intraocular pressure (IOP), body mass index (BMI), education level, systolic blood pressure, axial length, and statin medication. Using 5 IVs identified from the GWAS and with the inverse variance weighted MR method, we found that higher levels of HDL3 cholesterol were associated with a decreased odds of POAG (OR, 0.91; 95% CI, 0.84–0.99, P = 0.021). Other MR methods, including weighted median, mode-based estimator, and contamination mixture methods, derived consistent OR estimates. None of the routine lipids (blood total, HDL, or low-density lipoprotein [LDL] cholesterol) were associated with POAG. Conclusions Overall, these results suggest that the relationship between HDL3 cholesterol and POAG might be causal and specific, and that dysregulation of cholesterol transport may play a role in the pathogenesis of POAG.

Abstract: In this review, an effort towards presenting an all-around account of the recent progress on the natural product, aloperine, is made, and the antivirus structure-activity relationship of its derivatives is also summarized comprehensively. In addition, the principal pharmacological effects and corresponding molecular mechanisms of aloperine are discussed. Some new structural modifications of aloperine are also given, which might provide brief guidance for further investigations on the natural product aloperine.

Two-dimensional (2D) ZnSnO3 is a promising candidate for future gas sensors due to its high chemical response and excellent electronic properties. However, the preparation of 2D ZnSnO3 nanosheets by utilizing soluble inorganic salts and nonorganic solvents remains a challenge. In this work, 2D ZnSnO3 was synthesized via a facile graphene oxide (GO)-assisted co-precipitation method, in which inorganic salts in the aqueous phase replaced metal organic salts in a non-aqueous system. Meanwhile, a “dissolution and recrystallization” mechanism was proposed to explain the transformation from 3D nanocubes to 2D nanosheets. In comparison, the 2D ZnSnO3 nanosheets showed a higher response to formaldehyde (HCHO) at low operating temperature (100 °C). The response (Ra/Rg) of the 2D ZnSnO3 sensor to 10 ppm HCHO was as high as 57, which was approximately 5 times the response of the ZnSnO3 nanocubes sensor. However, the ZnSnO3 nanocubes sensor showed better gas sensing performance to ethanol at high temperature (200 °C). Different gas-sensitive properties were attributed to the different gas diffusion and adsorption processes caused by the morphology and nanostructure. Moreover, both sensors could detect either 0.1 ppm HCHO or ethanol at their optimum operating temperature. This work presents a relatively economical method to prepare 2D compound metal oxides, provides a novel “dissolution and recrystallization” mechanism for 2D multi-metal oxide preparation, and sheds light on the great potential of high-efficiency HCHO and/or ethanol gas sensors.

A kind of graphitic carbon nitride (TSC−550) with high polymerization degree and improved surface property was prepared by a new precursor of thiosemicarbazide. The sulfur motif and high nitrogen content in thiosemicarbazide promoted the polymerization of thiosemicarbazide to form graphitic carbon nitride framework with high degree of polymerization, which significantly influenced the electronic structure and surface chemical properties. TSC−550 possessed a narrow bandgap of 2.19 eV that facilitated the utilization of visible light, and possessed a less positive charge, acidic surface that resulted in enhanced hydrogen adsorption ability in water solution, which promoted the H2 evolution kinetics. In addition, the extended π-conjugated electronic system promoted the separation and migration of photo-generated charge carries in plane of TSC−550 framework, as well as the increasing interlayer C–N interactions in TSC−550 created conductive paths across the layers to tunnel interlayers for rapid electron transportation. As a result, TSC−550 nanosheets showed excellent photocatalytic H2 production activity, the AQY achieved 36.4% at 425 nm.

Overexpression of various pro-inflammatory factors in microglial cells tends to induce neurodegenerative diseases, for which there is no effective therapy available. Aureonitol (1) and seven analogues, including six previously undescribed [elatumenol A-F (2-4, 6-8, respectively)], along with two new orsellinic acid esters [elatumone A and B (9 and 10)], were isolated from Chaetomium elatum. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including high-resolution mass spectra and one- and two-dimensional NMR, and absolute configurations determined by the Mosher method, dimolybdenum tetraacetate-induced circular dichroism, and theoretical calculations including electronic circular dichroism and NMR. Metabolites 3, 4, 7, and 8 exhibited antineuroinflammatory activity by attenuating the production of inflammatory mediators, such as nitric oxide, interleukin-6, interleukin-1β, tumor necrosis factor-α, and reactive oxygen species. Western blot results indicated 8 decreases the level of inducible nitric oxide synthase and cyclooxygenase-2 and suppresses the expression of Toll-like receptor 4 and nuclear factor kappa-B (NF-κB) as well as the phosphorylation of the inhibitor of NF-κB and p38 mitogen-activated protein kinases in lipopolysaccharide-activated BV-2 microglial cells.

Three-dimensional carbon aerogel (CA800) was prepared from waste corrugated cardboard (WCC) by the procedure of slurrying, solvent replacement, drying, and carbonization in turn, and the product was explored as an all-in-one evaporator for solar steam generation without bulk water. Carbonization of the precursor was investigated using thermogravimetric analyzer coupled with Fourier transform infrared spectrometer. Results showed that CO2, CO, furfural, and levoglucosan were released during pyrolysis of WCC within the range of 300 to 390 °C, while polymerization of newly formed char between 390 and 580 °C mainly resulted in the formation of CO2 and CO. Both pyrolysis and polymerization reactions can be described by diffusion-controlled mechanisms, and the activation energies were 155.62 and 11.17 kJ mol−1, respectively. CA800 possessed a BET surface area of 210 m2 g−1. Light can be effectively absorbed and converted into heat by CA800, and its surface temperature achieving 73 °C under 1 kW m−2 irradiation. CA800 had outstanding wettability due to the presence of hydrophilic minerals in carbon matrix, and it was able to store as much as 15 times its own weight in water due to its abundant interconnected channels and hierarchical nanopores. Solar-driven water evaporation rate over CA800 achieved 1.72 kg m−2 (normalized to projection area), which was nearly 6 times higher than the value achieved by the bare water system. The photothermal conversion efficiency was calculated to be 118 %, and the overestimated efficiency was caused by the environmental energy gained by the cold evaporation surface of CA800.

A novel but simple design is presented of a multi-ion network with polyamic acid that combines high extensibility and toughness with spontaneous healing ability. Taking advantage of the carboxylate structure of polyamic acid, the introduction of a sufficient number of metal ions to neutralize the carboxylated groups can form reversible ionic bonds within the polymeric network. Dry-solid zinc(II)-poly(amic acid-PDMS) is transparent and exhibits good mechanical properties, including good ultimate strength (~0.267 MPa) and high stretchability (~360%). In addition, this dynamic network can self-heal at ambient temperature without requiring stimulation from heat, a plasticizer, or a solvent. The very simple method of our proposed polyamic acid polymers opens up the possibility of increasingly utilizing high-performance, low-cost, and environmentally friendly polyamic acids instead of polyimides. A simplified multi-ion network is presented, which can toughen and modulate the spontaneous self-healing capability of dry-solid Zn(II)-carboxylate polyamic acid under ambient conditions.

G-quadruplex (G4) ligand-induced DNA damage has been involved in many physiological functions of cells. Herein, cationic porphyrin (TMPyP4)-mediated DNA oxidation damage was investigated aiming at mitochondrial G4 DNA (mt9438) and its structural analogue of the thrombin-binding aptamer (TBA). TMPyP4 is found to stabilize TBA G4 but destabilize mt9438. For two resulting DNA-TMPyP4 assemblies, the distinct light-induced singlet oxygen (1O2) generation and the subsequent DNA damage were found. For mt9438-TMPyP4, a slower 1O2-induced DNA damage takes place and results in the formation of DNA aggregation. In contrast, 1O2 tends to promote DNA unfolding in a relatively faster rate for TBA-TMPyP4. Despite of such distinct DNA damage behavior, UV resonance Raman spectra reveal that for both mt9438-TMPyP4 and TBA-TMPyP4 the DNA damage commonly stems from the guanine-specific oxidation. Our results clearly indicate that the ligand-mediated DNA damage is strongly dependent on the initial interplay between DNA and the ligand.

Successful synthesis of glyconanoparticles has attracted much attention due to their various biointeractive capabilities, but it is still a challenge to understand different single-cell responses to exogenous particles among cell populations. Herein, we designed polyaniline-containing galactosylated gold nanoparticles (Au@PGlyco NPs) via in situ polymerization of ortho-nitrophenyl-β-galactoside assisted by Au nucleation. The nanogold-carrying polyaniline block produced electromagnetic enhancement in surface-enhanced Raman scattering (SERS). The underlying polymerization mechanism of ortho-nitrophenyl compounds via the formation of Au nanoparticles was investigated. Depending on how the galactoside moiety reacted with β-galactosidase derived from bacteria, the Au@PGlyco NPs-mediated SERS biosensor could detect low amounts of bacteria (∼1 × 102 CFU/mL). In addition, a high accumulation of Au@PGlyco NPs mediated the immune response of tumor-associated M2 macrophages to the immunogenic M1 macrophage transition, which was elicited by reactive oxygen levels biostimulation using single-cell SERS-combined fluorescence imaging. Our study suggested that Au@PGlyco NPs may serve as a biosensing platform with the labeling capacity on galactose-binding receptors expressed cell and immune regulation.

A novel nucleophilic reaction between cyclic ethers and benzyl bromides is achieved under photoredox catalysis. The reaction proceeds through a single-electron-transfer (SET) pathway rather than a common SN2 mechanism. By two steps of reduction and oxidation, a benzyl bromide heterolyzes to give a carbocation and bromide ion under mild conditions, and then a cyclic ether captures both the carbo­cation and bromide ion to afford the addition product.

AimsTo report the 6-year incidence of optical coherence tomography (OCT)-derived age-related changes in drusen volume and related systemic and ocular associations.MethodsChinese adults aged 40 years and older were assessed at baseline and 6 years with colour fundus photography (CFP) and spectral domain (SD) OCT. CFPs were graded for age-related macular degeneration (AMD) features and drusen volume was generated using commercially available automated software.ResultsA total of 4172 eyes of 2580 participants (mean age 58.12±9.03 years; 51.12% women) had baseline and 6-year follow-up CFP for grading, of these, 2130 eyes of 1305 participants had gradable SD-OCT images, available for analysis. Based on CFP grading, 136 (3.39%) participants developed incident early AMD and 10 (0.25%) late AMD. Concurrently, retinal pigment epithelial-Bruch’s membrane (RPE-BrC) volumes decreased, remained stable and increased in 6.8%, 78.5% and 14.7%, respectively, over 6 years. In eyes where RPE-BrC volumes were >0 mm3at baseline, this was associated with two-fold higher prevalence rate of any AMD at baseline (pConclusionAMD incidence detected at 6 years on CFP and correlated OCT-derived drusen volume measurement change is low. Older age and some systemic risk factors are associated with drusen volume change, and our data provide new insights into relationship between systemic risk factors and outer retinal morphology in Asian eyes.

Hydroalkylation, the direct addition of a C(sp3)–H bond across an olefin, is a desirable strategy to produce valuable, complex structural motifs in functional materials, pharmaceuticals, and natural products. Herein, we report a reliable method for accessing α-branched amines via nickel-catalyzed hydroalkylation reactions. Specifically, by using bis(cyclooctadiene)nickel (Ni(cod)2) together with a phosphine ligand, we achieved a formal C(sp3)–H bond insertion reaction between olefins and N-sulfonyl amines without the need for an external hydride source. The amine not only provides the alkyl motif but also delivers hydride to the olefin by means of a nickel-engaged β–hydride elimination/reductive elimination process. This method provides a platform for constructing chiral α-branched amines by using a P-chiral ligand, demonstrating its potential utility in organic synthesis. Notably, a sulfonamidyl boronate complex formed in situ under basic conditions promotes ring-opening of the azanickellacycle reaction intermediate, leading to a significant improvement of the catalytic efficiency., Catalytic addition of a carbon chain and a hydrogen across a double bond has often required an added hydride source. Here the authors show a method to add alkanes with an amino functionality to olefins, wherein a nickel catalyst uses the amine itself as the hydride source, obviating an external hydride reagent.

The structural tailoring of pores is essential to high-performance Fe/N/C electrocatalysts for the oxygen reduction reaction (ORR) in proton exchange membrane fuel cells. Current strategies for pore structure engineering are usually accompanied with a drastic change of the intrinsic activity-related surface, which may mask the real effects of the porous structure on ORR activity. Herein, a mild carbon dioxide (CO2) etching method was used to flexibly tailor the pore structure of Fe/N/C electrocatalysts without drastic changes in their surface structure and property. In this way, via employing the Fe/N/C electrocatalysts as a model, the intrinsic impact of the pore structure on ORR activity was revealed. In addition, the CO2 etching method developed a high-quality electrocatalyst (sample Fe/N/C-5% CO2) with polarization performance exceeding that of the commercial Pt/C catalyst in the fuel cell working voltage region (>0.65 V). This work will promote the ongoing intensive studies on the rational design of the pore structures in the Fe/N/C electrocatalysts.

Hydrogen (H2) molecules are easy to leak during production, storage, transportation and usage. Because of their flammability and explosive nature, quick and reliable dectection of H2 molecule is of great significance. Herein, an excellent H2 gas sensor has been realized based on Pd nanocrystal sensitized two-dimensional (2D) porous TiO2 (Pd/TiO2). The formation of 2D porous TiO2 with the removal of graphene oxide template has been monitored by an in-situ transmission electron microscope. It is found that the size of the GO template can be almost completely replicated by 2D TiO2. The Pd/TiO2 sensor exhibited an instantaneous response and a satisfactory low detection limit for H2 detection. These excellent gas-sensing performances (good selectivity, unique linearity response and high stability) can be attributed to the unique 2D porous structure and the synergistic effect between oxidized Pd and TiO2, including the unique adsorption properties of O2 or/and H2 on Pd/TiO2, the reaction between PdO and H2 gas, and the regulated depletion layer arising from p-type PdO to n-type TiO2. This work demonstrates a rational design and synthesis of highly efficient H2 sensitive materials for energy and manufacturing security.

Zeolitic imidazolate framework-67 (ZIF67) has been regarded as an effective energy storage material due to its high surface area and electroactive cobalt center. Carbonizing ZIF67 can enhance electrical conductivity by converting 2-methylimidazole (2-melm) to carbon with cobalt doping. In this work, a novel in situ electrospinning is proposed to fabricate carbonized ZIF67 on carbon fiber (C67@PAN-OC) as a freestanding supercapacitor electrode. Polyacrylonitrile solution containing a cobalt precursor is used for electrospinning, and produced fibers are immersed in 2-melm to form ZIF67. Individually grown carbonized ZIF67 on carbon fiber is obtained using the in situ electrospinning method, while the one-body mixed carbon electrode is formed using the ex situ electrospinning method. A highest specific capacitance (CF) of 386.3 F/g at 20 mV/s is obtained for the in situ synthesized C67@PAN-OC electrode due to the largest electrochemical surface area and the smallest resistance, while the ex situ synthesized electrode only shows a CF value of 27.7 F/g. A symmetric supercapacitor (SSC) assembled using the optimized C67@PAN-OC electrodes and gel electrolytes shows a maximum energy density of 9.64 kWh/kg at 0.55 kW/kg and a CF retention of 59.5% after 1000 times charge/discharge process. A CF retention of 75.6% after bending 100 times is also obtained for SSC.

The identification of the generation pathway of •OH radical during the oxygen reduction reaction (ORR) is critical because it determines which strategy should be adopted to minimize these corrosive species. In this way, researchers can develop a more stable Fe/N/C ORR catalyst or a catalyst layer in the proton exchange membrane fuel cells (PEMFCs). To date, this critical problem has still been unresolved. Herein, the generation of the •OH radical during the acidic ORR was mimicked by using two known pathways, that is, the Fenton (and Fenton-like) and the electrochemical reduction of H2O2(H2O2-ECR) process. The latter was determined as the main generation pathway of •OH radical below 30 °C. As the temperature surpassed 30 °C, the H2O2-ECR process began to lose its dominance because of the appearance of a third so-far unknown generation pathway. This work lays a basis for future development of radical elimination strategies to stabilize a Fe/N/C ORR catalyst or a catalyst layer in PEMFCs.

pH shift is an effective technique for modifying functional properties of food proteins. However, it can increase lysinoalanine (LAL) content under alkali conditions, thus limiting the use of proteins. This study investigated the inhibition effect of ultrasonic parameters on LAL formation in rapeseed protein isolates (RPI) during pH shift treatment (pH-ST). Results showed that the content of LAL decreased by 49.5% and 74.1%, following the use of ultrasound (28 kHz, 40 W/L, 40 °C, and 30 min) under alkali and acidic treatment, respectively. Structural analysis showed that after ultrasonic irradiation, increased sulfhydryl groups and amino acids reduced the dehydroalanine and, thus, decreased LAL content. Particle size, secondary structure, and microstructure (SEM, AFM) analyses showed relative dispersion in protein distribution, reducing intermolecular or intramolecular cross-linking, thereby lowering the LAL content. Thus, ultrasonic-aided pH-ST may be an operational technique toward minimizing LAL formation in RPI.

Lagotis brachystachya Maxim is an herb widely used in traditional Tibet medicine. Our previous study indicated that total extracts from Lagotis brachystachya could lower uric acid levels. This study aimed to further elucidate the active components (luteolin, luteoloside and apigenin) isolated from Lagotis brachystachya and the underlying mechanism in vitro and vivo. The results showed that treatment with luteolin and luteoloside reversed the reduction of organic anion transporter 1 (OAT1) levels, while apigenin attenuated the elevation of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) levels in uric acid-treated HK-2 cells, which were consistent with the finding in the kidney of potassium oxonate (PO)-induced mice. On the other hand, hepatic xanthine oxidase activity was inhibited by the components. In addition, all of these active components improved the morphology of the kidney in hyperuricemic mice. Moreover, molecular docking showed that luteolin, luteoloside and apigenin could bind TLR4 and NLRP3. Consistently, western blot showed that the components inhibited TLR4/MyD88/NLRP3 signaling. In conclusion, these results indicated that luteolin, luteoloside and apigenin could attenuate hyperuricemia by decreasing the production and increasing the excretion of uric acid, which were mediated by the inhibition of inflammatory signaling pathways.

With the decreasing size of the integrated circuits, developments of materials with low dielectric constant have become an important research to solve the problems of parasitic capacitance. Thus in this study, low-cost SiO2 and polylactic acid (PLA) were used for the fabrication of SiO2/PLA hybrid films targeting capacitor applications. SiO2 nanoparticles with porous structure were prepared via spray pyrolysis with non-ionic surfactant F-127 as a pore-forming agent. In addition, surface morphology, porous structure, specific surface area, and particle porosity were examined via X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and nitrogen adsorption/desorption isotherms, respectively. Then, the SiO2/PLA hybrid films were fabricated and the resulting dielectric constants were measured. Finally, the resulting morphologies and properties and the corresponding mechanisms were discussed.

Background and Objectives: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) significantly reduce the risk of cardiovascular events in patients with type 2 diabetes mellitus (T2DM). However, the effectiveness of SGLT2is in heart failure (HF) treatment has not yet been established. The aim of this meta-analysis was to assess the efficacy and safety of SGLT2is in HF treatment by focusing on cardiovascular death (CVD), hospitalization for HF (HHF), and a composite of CVD and HHF. Methods: We searched literature sources in PubMed, EMBASE, and Cochrane Library up until December 20, 2020. Only randomized controlled trials were included in this meta-analysis. We compared the treatment and placebo groups in terms of their associated risks of CVD and HHF and their safety endpoints. The Cochrane tool for assessing risk of bias in randomized trials was applied. Results: The 10 selected studies included 17,043 HF patients and dapagliflozin, empagliflozin, canagliflozin, ertugliflozin, and sotagliflozin as experimental arms. At least 4 included studies were with high quality. For CVD, HHF, and their composite, the pooled risk ratio estimates were 0.87 (95% confidence interval [CI], 0.78–0.96; P = 0.004), 0.70 (95% CI, 0.65–0.76; P < 0.001), and 0.76 (95% CI, 0.71–0.81; P < 0.001), respectively. The incidence of volume depletion, hypoglycemia events, fractures, acute renal injury, and urogenital tract infection was not significantly higher in the SGLT2i group than in the placebo group. Stratified analyses showed similar efficacy and safety results for HF patients with T2DM, those without T2DM, and those being treated with different types of SGLT2is. Conclusions: This meta-analysis demonstrated that various SGLT2is significantly decreased the risks of CVD and HHF in HF patients with and without T2DM. It also showed that clinical administration of SGLT2is was relatively safe in terms of the aforementioned risk factors. SGLT2is might embrace broader clinical application in future HF treatment.

Marine natural products play critical roles in the chemical defense of many marine organisms and are essential, reputable sources of successful drug leads. Sixty-seven 14-membered resorcylic acid lactone derivatives 3–27 and 30–71 of the natural product zeaenol (1) isolated from the marine-derived fungus Cochliobolus lunatus were semisynthesized by chlorination, acylation, esterification, and acetalization in one to three steps. The structures of these new derivatives were established by HRESIMS and NMR techniques. All the compounds (1–71) were evaluated for their antialgal and antiplasmodial activities. Among them, 14 compounds displayed antifouling activities against adhesion of the fouling diatoms. In particular, 9 and 34 exhibited strong and selective inhibitory effects against the diatoms Navicula laevissima and Navicula exigua (EC50 = 6.67 and 8.55 μmol/L), respectively, which were similar in efficacy to those of the positive control SeaNine 211 (EC50 = 2.90 and 9.74 μmol/L). More importantly, 38, 39, and 69–71 showed potent antiplasmodial activities against Plasmodium falciparum with IC50 values ranging from 3.54 to 9.72 μmol/L. Very interestingly, the five antiplasmodial derivatives displayed non-toxicity in the cytotoxicity assays and the zebrafish embryos model, thus, representing potential promising antiplasmodial drug agents. The preliminary structure–activity relationships indicated that biphenyl substituent at C-2, acetonide at positions C-5′ and C-6′, and tri- or tetra-substituted of acyl groups increased the antiplasmodial activity. Therefore, combining evaluation of chemical ecology with pharmacological models will be implemented as a systematic strategy, not only for environmentally friendly antifoulants but also for structurally novel drugs.

Epigenetic manipulation of a deep-sea sediment-derived Spiromastix sp. fungus using suberoylanilide hydroxamic acid (SAHA) induction resulted in the activation of a terpene-related biosynthetic gene cluster, and nine new guaiane-type sesquiterpenes, spiromaterpenes A-I (1-9), were isolated. Their structures were determined using various spectroscopic techniques, in association with the modified Mosher's method, computed electronic circular dichroism (ECD) spectra, and chemical conversion for configurational assignments. Compounds 4-6 exhibited significant effects against the NO production on lipopolysaccharide (LPS)-induced microglia cells BV2, and the preliminary SAR analyses demonstrated that a 2(R),11-diol unit is favorable. The most active 5 abolished LPS-induced NF-κB translocation from the cytosol to the nucleus in BV-2 microglial cells, accompanied by the marked reduction of the transcription levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α dose-dependently in both LPS-induced BV-2 and BV-2 cells, as well as the protein and mRNA levels of iNOS and COX-2. This study complements the gap in knowledge regarding the anti-neuroinflammatory activity of guaiane-type sesquiterpenoids at the cellular level and suggests that 5 is promising for further optimization as a multifunctional agent for antineuroinflammation.

Dephosphorylation that removes a phosphate group from substrates is an important reaction for living organisms and environmental protection. Although CeO2 has been shown to catalyze this reaction, cerium is low in natural abundance and has a narrow global distribution (>90 % of these reserves are located within six countries). It is thus imperative to find another element/material with high worldwide abundance that can also efficiently extract the phosphate out of agricultural waste for phosphorus recycle. Using para-nitrophenyl phosphate (p-NPP) as a model compound, we demonstrate that TiO2 with a F-modified (001) surface can activate p-NPP dephosphorylation at temperatures as low as 40 °C. By probe-assisted nuclear magnetic resonance (NMR), it was revealed that the strong electron-withdrawing effect of fluorine makes Ti atoms (the active sites) on the (001) surface very acidic. The bidentate adsorption of p-NPP on this surface further promotes its subsequent activation with a barrier ≈20 kJ mol-1 lower than that of the pristine (001) and (101) surfaces, allowing the activation of this reaction near room temperature (from >80 °C).

Haw-Ming Huang,1,2 Ping-Han Wu,3 Po-Chien Chou,4 Wen-Tien Hsiao,5 Hsin-Ta Wang,4 Hsin-Pei Chiang,3 Chi-Ming Lee,6 Shwu-Huey Wang,6 Yu-Cheng Hsiao2,7 1School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; 2Graduate Institute of Biomedical Optomechatronics, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 3Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 4School of Organic and Polymeric, National Taipei University of Technology, Taipei, Taiwan; 5Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan; 6Core Facility Center, Office of Research and Development, Taipei Medical University, Taipei, Taiwan; 7Cell Physiology and Molecular Image Research Center, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, TaiwanCorrespondence: Yu-Cheng Hsiao; Ping-Han WuTaipei Medical University, No. 250, Wu-Hsing Street, Taipei, 11031, TaiwanTel +886-291-937-9783Fax +886 2 27362295Email ychsiao@tmu.edu.tw; gahwclbjwph@gmail.comIntroduction: It has been reported that low-molecular-weight hyaluronic acid (LMWHA) exhibits a potentially beneficial effect on cancer therapy through targeting of CD44 receptors on tumor cell surfaces. However, its applicability towards tumor detection is still unclear. In this regard, LMWHA-conjugated iron (Fe3O4) nanoparticles (LMWHA-IONPs) were prepared in order to evaluate its application for enhancing the T2* weighted MRI imaging sensitivity for tumor detection.Methods: LMWHA and Fe3O4 NPs were produced using γ-ray irradiation and chemical co-precipitation methods, respectively. First, LMWHA-conjugated FITC was prepared to confirm the ability of LMWHA to target U87MG cells using fluorescence microscopy. The hydrodynamic size distribution and dispersion of the IONPs and prepared LMWHA-IONPs were analyzed using dynamic light scattering (DLS). In addition, cell viability assays were performed to examine the biocompatibility of LMWHA and LMWHA-IONPs toward U87MG human glioblastoma and NIH3T3 fibroblast cell lines. The ability of LMWHA-IONPs to target tumor cells was confirmed by detecting iron (Fe) ion content using the thiocyanate method. Finally, time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging and in vitro magnetic resonance imaging (MRI) were performed to confirm the contrast enhancement effect of LMWHA-IONPs.Results: Florescence analysis results showed that LMWHA-FITC successfully targeted the surfaces of both tested cell types. The ability of LMWHA to target U87MG cells was higher than for NIH3T3 cells. Cell viability experiments showed that the fabricated LMWHA-IONPs possessed good biocompatibility for both cell lines. After co-culturing test cells with the LMWHA-IONPs, detected Fe ion content in the U87MG cells was much higher than that of the NIH3T3 cells in both thiocyanate assays and TOF-SIMs images. Finally, the addition of LMWHA-IONPs to the U87MG cells resulted in an obvious improvement in T2* weighted MR image contrast compared to control NIH3T3 cells.Discussion: Overall, the present results suggest that LMWHA-IONPs fabricated in this study provide an effective MRI contrast agent for improving the diagnosis of early stage glioblastoma in MRI examinations.Keywords: hyaluronic acid, Fe3O4 nanoparticles, TOF-SIMS, MRI

Natural products derived from marine microorganisms have received great attention as a potential resource of new compound entities for drug discovery. The unique marine environment brings us a large group of sulfur-containing natural products with abundant biological functionality including antitumor, antibiotic, anti-inflammatory and antiviral activities. We reviewed all the 484 sulfur-containing natural products (non-sulfated) isolated from marine microorganisms, of which 59.9% are thioethers, 29.8% are thiazole/thiazoline-containing compounds and 10.3% are sulfoxides, sulfones, thioesters and many others. A selection of 133 compounds was further discussed on their structure–activity relationships, mechanisms of action, biosynthesis, and druggability. This is the first systematic review on sulfur-containing natural products from marine microorganisms conducted from January 1987, when the first one was reported, to December 2020.

Potassium ion (K+) plays a crucial role in biological systems, such as maintaining cellular processes and causing diseases. However, specifically, the detection of K+ is extremely challenging because of the coexistence of the chemically similar ion of Na+ under physiological conditions. In this work, a K+ specific biosensor is constructed on the basis of a dimerized G-quadruplex (GQ) DNA, which is promoted by K+, and the enzymatic activity of the resulting DNAzyme depends on the concentration of the K+. The K+ in a 1-200 mM concentration range can be selectively detected by visual color, UV-Vis absorbance or fluorescence even if the concentration of the accompanying Na+ is up to 140 mM at an ambient condition up to 45 °C. In addition, this system can also be used to selectively detect NH4+ in a 5-200 mM concentration range. This dimerized DNAzyme offers a new type of biosensor with a potential application in the biological system.

Hybrid MXene/reduced graphene oxide aerogel microspheres (MXene/rGOAMs),where MXenes are two-dimensional (2D) transition metal carbides, with abundant macro/meso/micro multi-scale pores and self-supporting structure, are prepared by electrospraying followed by freeze-drying and then thermal annealing. A center-diverging structure with well-aligned microchannels is formed within each microsphere, which can be maintained after thermal reduction. Such highly ordered 3D hybrid mesoporous network has been tested for the hydrogen evolution reaction (HER) because it may prevent the stacking of the 2D layers, thus enhancing the mass transfer. Actually, in the case of Ti3C2Tx/rGOAMs, obtained with an optimized MXene:GO mass ratio and after a thermal treatment at 400 °C, a better HER performance with respect to the bulk Ti3C2Tx aerogel or the MXene/GO composite is observed (η10=-336 mV), suggesting an accelerated mass transfer through different inter-sheets when the 3D mesoporous microsphere networks are created. The Ti3C2Tx/rGOAMs also exhibit enhanced HER activity compared to rGOAMs, suggesting that the MXene plays a key role due to the presence of titanium atoms with a low valence state.

The discovery of dynamic and reversible modifications in RNA expands their functional repertoires. Now, RNA modifications have been viewed as new regulators involved in a variety of biological processes. Among these modifications, thiolation is one kind of special modification in RNA. Several thiouridines have been identified to be present in RNA, and they are essential in the natural growth and metabolism of cells. However, detection of these thiouridines generally is challenging, and few studies could offer the quantitative levels of uridine modifications in RNA, which limits the in-depth elucidation of their functions. Herein, we developed a chemical derivatization in combination with mass spectrometry analysis for the sensitive and simultaneous determination of uridine thiolation and hydroxylation modifications in eukaryotic RNA. The chemical derivatization strategy enables the addition of easily ionizable groups to the uridine thiolation and hydroxylation modifications, leading up to a 339-fold increase in detection sensitivities of these modifications by mass spectrometry analysis. The limits of detection of these uridine modifications can be down to 17 amol. With the established method, we discovered and confirmed that a new modification of 5-hydroxyuridine (ho5U) was widely present in small RNAs of mammalian cells, expanding the diversity of RNA modifications. The developed method shows superior capability in determining low-abundance RNA modifications and may promote identifying new modifications in RNA, which should be valuable in uncovering the unknown functions of RNA modifications.

Tritium with different chemical forms have different effects on the human body. In tritium migration and conversion, soil plays a significant role. In this study, our samples are from the surrounding environment of the Qinshan Nuclear Power Plant, in addition, Qinshan Phase III Nuclear Power Plant is the only heavy water reactor nuclear power plant (CANDU type, 700 MWe) in China. Both tritiated water (HTO) and non-exchangeable organically bound tritium (NE-OBT) were measured at the surface soil (0–2 cm) at 8 sampling sites and their depth profiles in the subsurface 30 cm of soil in two sampling sites around Qinshan Nuclear Power Plant in 2015, 2016 and 2018. The distribution analysis showed the further away from the nuclear power plant, the lower activity concentration of HTO at the surface soil. Also, in the depth profile, the HTO activity concentration decreased as the depth increase. Through soil analysis at different depths of sampling points A and D, it is concluded that the activity concentration of NE-OBT is the largest in the surface soil of the selected sampling points, which is similar to the HTO of most sampling points.

Two novel natural products, beetleane A (1) and epicoane A (2), were obtained from the metabolites of an endophytic Epicoccum nigrum. Compound 1 has a unique beetlelike structure that is constructed by the fusion and further fold of an unusual [5.5.5.6]trioxafenestrane with a cycloheptane ring. Compound 2 possesses a compact cagelike structure with a unique 6/5/5/5/6/6/5 heptacyclic ring system. Both 1 and 2 showed strong antiliver fibrosis activity in vitro.

Lignin has been used as a sustainable and eco-friendly filler in composite fibers. However, lignin aggregation occurred at high lignin content, which significantly hindered the further enhancement of fiber performance. The incorporation of graphene oxide (GO) enhanced the mechanical properties of the lignin/poly(vinyl alcohol) (PVA) fibers and affected their structure. With the GO content increasing from 0 to 0.2%, the tensile strength of 5% lignin/PVA fibers increased from 491 MPa to 631 MPa, and Young's modulus increased from 5.91 GPa to 6.61 GPa. GO reinforced 30% lignin/PVA fibers also showed the same trend. The tensile strength increased from 455 MPa to 553 MPa, and Young's modulus increased from 5.39 GPa to 7 GPa. The best mechanical performance was observed in PVA fibers containing 5% lignin and 0.2% GO, which had an average tensile strength of 631 MPa and a Young’s modulus of 6.61 GPa. The toughness values of these fibers are between 9.9-15.6 J/g, and the fibrillar and ductile fracture microstructure were observed. Structure analysis of fibers showed that GO reinforced 5% lignin/PVA fibers had higher crystallinity, and evidence of hydrogen bonding among GO, lignin, and PVA in the gel fibers was revealed. Further, water resistance and swelling behavior of composite PVA fibers were studied to further evidence the structure change of composite fibers.

The dynamic assembly of the cell wall is key to the maintenance of cell shape during bacterial growth. Here, we present a method for the analysis of Escherichia coli cell wall growth at high spatial and temporal resolution, which is achieved by tracing the movement of fluorescently labeled cell wall-anchored flagellar motors. Using this method, we clearly identify the active and inert zones of cell wall growth during bacterial elongation. Within the active zone, the insertion of newly synthesized peptidoglycan occurs homogeneously in the axial direction without twisting of the cell body. Based on the measured parameters, we formulate a Bernoulli shift map model to predict the partitioning of cell wall-anchored proteins following cell division., Dynamic cell wall assembly is key to cell shape maintenance during bacterial growth. Here, the authors present a method that allows high-resolution analysis of active and inert zones of cell wall growth during bacterial elongation. They also formulate a mathematical model to predict the partitioning of cell wall-anchored proteins following cell division.

Photocatalytic overall water splitting can be achieved using Z-scheme systems that mimic natural photosynthesis by combining dissimilar semiconductors in series. However, coupling well-suited H2- and O2-evolving components remains challenging. Here, we fabricate a Z-scheme system for photocatalytic overall water splitting based on boron-doped, nitrogen-deficient carbon nitride two-dimensional (2D) nanosheets. We prepare ultrathin carbon nitride nanosheets with varying levels of boron dopants and nitrogen defects, which leads to nanosheets that can act as either H2- or O2-evolving photocatalysts. Using an electrostatic self-assembly strategy, the nanosheets are coupled to obtain a 2D/2D polymeric heterostructure. Owing to their ultrathin nanostructures, strong interfacial interaction and staggered band alignment, a Z-scheme route for efficient charge-carrier separation and transfer is realized. The obtained heterostructure achieves stoichiometric H2 and O2 evolution in the presence of Pt and Co(OH)2 co-catalysts, and the solar-to-hydrogen efficiency reaches 1.16% under one-sun illumination. Splitting water using suspensions of particulate carbon nitride-based photocatalysts may be a cheap way to produce hydrogen, but efficiencies have remained low. Now, Shen and colleagues use doped carbon nitride-based Z-scheme heterostructures to split water with a solar-to-hydrogen efficiency of 1.1% in the presence of metal-based co-catalysts.

Fong-Yu Cheng,1 Yuan-Yow Chiou,2,3 Shih-Yuan Hung,4,5 Tsun-Mei Lin,6 Hao-Kuang Wang,7 Chi-Wei Lin,8 Hung-Hsiang Liou,9 Min-Yu Chang,5 Hsi-Hao Wang,5 Yi-Che Lee4,5,10 1Department of Chemistry, Chinese Culture University, Taipei, Taiwan; 2Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan; 3Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 5Division of Nephrology, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan; 6Department of Laboratory Medicine, E-DA Hospital, Kaohsiung, Taiwan; 7Department of Neurosurgery, E-DA Hospital, Kaohsiung, Taiwan; 8Department of Medical Education, E-DA Hospital, Kaohsiung, Taiwan; 9Division of Nephrology, Department of Internal Medicine, Hsin-Jen Hospital, New Taipei City, Taiwan; 10Division of Nephrology, Department of Internal Medicine, E-DA Dachang Hospital, Kaohsiung, TaiwanCorrespondence: Yi-Che LeeDivision of Nephrology, Department of Internal Medicine, E-DA Hospital/I-Shou University, No.1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445, Taiwan, R.O.CTel +886-7-6150011 Ext 5121Email pipijer@gmail.comPurpose: Vitamin D3 is useful for the treatment of peritoneal dialysis (PD)-related peritoneal damage, but its side effects, such as hypercalcemia and vascular calcification, limit its applicability. Thus, we developed vitamin D-loaded magnetic nanoparticles (MNPs) and determined their therapeutic efficacy and side effects in vivo.Materials and Methods: Alginate-modified MNPs were combined with 1α, 25 (OH)2D3 to generate vitamin D-loaded nanoparticles. The particles were conjugated with an antibody against peritoneum-glycoprotein M6A (GPM6A). The particles’ ability to target the peritoneum was examined following intraperitoneal administration to mice and by monitoring their bio-distribution. We also established a PD animal model to determine the therapeutic and side effects of vitamin D-loaded MNPs in vivo.Results: Vitamin D-loaded MNPs targeted the peritoneum better than vitamin D3, and had the same therapeutic effect as vitamin D3 in ameliorating peritoneal fibrosis and functional deterioration in a PD animal model. Most importantly, the particles reduced the side effects of vitamin D3, such as hypercalcemia and body weight loss, in mice.Conclusion: Vitamin D-loaded MNPs could be an ideal future therapeutic option to treat PD-related peritoneal damage.Keywords: peritoneal dialysis, nanoparticles, vitamin D, fibrosis

Objective To report two cases of for primary peritoneal serous carcinoma (PPSC) to present with gastrointestinal manifestations that mimic colorectal cancer. Case report There were two patients with initial presentations of fatigue with iron deficiency anemia, and tenesmus with bloody stool. Tumors of the ascending colon and rectum were detected by colonofiberoscope, and pathologic reports of tumor biopsies revealed adenocarcinoma of suspected gynecologic origin. Both patients underwent optimal debulking surgery without macroscopic residual tumor, and then received adjuvant carboplatin and paclitaxel chemotherapy with bevacizumab. Conclusions PPSC can clinically present like primary colorectal carcinoma. The differential diagnosis requires special staining of several markers for tumor tissues.

Previously, variation in retinal vascular caliber has been reported in association with chronic kidney disease (CKD) but findings remain inconsistent. To help clarify this we conducted individual participant data meta-analysis and aggregate data meta-analysis on summary estimates to evaluate cross-sectional associations between retinal vascular caliber and CKD. A systematic review was performed using Medline and EMBASE for articles published until October 2018. The aggregate analysis used a two-stage approach combining summary estimates from eleven studies (44,803 patients) while the individual participant analysis used a one-stage approach combining raw data from nine studies (33,222 patients). CKD stages 3-5 was defined as an estimated glomerular filtration rate under 60 mL/min/1.73m2. Retinal arteriolar and venular caliber (central retinal arteriolar and venular equivalent) were assessed from retinal photographs using computer-assisted methods. Logistic regression estimated relative risk of CKD stages 3-5 associated with a 20 μm decrease (approximately one standard deviation) in central retinal arteriolar and venular equivalent. Prevalence of CKD stages 3-5 was 11.2% of 33,222 and 11.3% of 44,803 patients in the individual participant and aggregate data analysis, respectively. No significant associations were detected in adjusted analyses between central retinal arteriolar and venular equivalent and CKD stages 3-5 in the aggregate analysis for central retinal arteriolar relative risk (0.98, 95% confidence interval 0.94-1.03); venular equivalent (0.99, 0.95-1.04) or individual participant central retinal arteriolar (0.99, 0.95-1.04) or venular equivalent (1.01, 0.97-1.05). Thus, meta-analysis provided little evidence to suggest that cross sectional direct measurements of retinal vascular caliber was associated with CKD stages 3-5 in the general population. Hence, meta-analyses of longitudinal studies evaluating the association between retinal parameters and CKD stages 3-5 may be warranted.

A polyrotaxane (PR) with poly(methyl methacrylate) (PMMA) as the main chain polymer was prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization. Because of the special mechanism of RAFT, the suprastructure of a PMMA-based PR is established by synthesizing inclusion complexes of methyl methacrylate and gamma-cyclodextrin (γCD) into the middle of the poly-N-(3-dimethylamino) propyl methacrylamide segments. The presence of threaded γCD was determined via diffusion ordered spectroscopy from the alignment of the mobility of γCD and the main chain polymer. A PMMA-based PR with 2-20% CD coverage and a molecular weight of 7K-60K g/mol of PMMA-based PR was synthesized with a targeted molecular structure by mediating the RAFT polymerization. The PMMA-based PR prepared in this study is expected to be suitable for wide applications of tough materials with good heat resistance. Moreover, the investigation of this synthetical approach opened possibilities for more variety of PR with controllable properties.

Background and aims Clarifying the association between 5-methyltetrahydrofolate and homocysteine and the effect pattern of methylene tetrahydrofolate reductase (MTHFR C677T) may contribute to the management of homocysteine and may serve as a significant reference for a randomized controlled trial of 5-methyltetrahydrofolate intervention. This study aimed to reveal the association between these two biochemical indices. Methods Study population was drawn from the baseline data of the China Stroke Primary Prevention Trial (CSPPT), including 2328 hypertensive participants. 5-methyltetrahydrofolate and homocysteine were determined by stable-isotope dilution liquid chromatography-tandem mass spectrometry and automatic clinical analyzers, respectively. MTHFR C677T polymorphisms were detected using TaqMan assay. Multiple linear regression was performed to evaluate the association between serum 5-methyltetrahydrofolate and homocysteine. Results There was a significant inverse association between 5-methyltetrahydrofolate and homocysteine when 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T (per 1-ng/mL increment; All: β = − 0.50, P β = − 0.14, P = 0.087; CT: β = − 0.20, P = 0.011; TT: β = − 1.19, P P for difference P for difference P for difference = 0.757). Conclusions Our data showed a non-linear association between serum homocysteine and 5-methyltetrahydrofolate among Chinese hypertensive adults, however, it could be inversely linearly fitted when serum 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T.

The discovery of different binding receptors to allow rapid and high-sensitivity detection via a noninvasive urine test has become the goal for urothelial carcinoma (UC) diagnosis and surveillance. In this study, we developed a new screening membrane receptor platform for bladder cancer cells by integrating surface-enhanced Raman spectroscopy (SERS) with 4-aminothiophenol (4-ATP)-modified AuAg nanohollows upon NIR laser excitation. AuAg nanohollows have an absorption band at ∼630 nm, and slightly off-resonance 785 nm laser excitation is used for minimal photothermal effect. Using the same carbodiimide cross-linker chemistry to conjugate anti-EGFR, transferrin (TF), 4-carboxyphenylboronic acid (CPBA), folic acid (FA), and hyaluronic acid (HA) molecules, by screening the 4-ATP SERS signals intensity, we demonstrated that the targeting efficiency with the cost-effective CPBA molecule is comparable with the conjugation of anti-EGFR antibody to aggressive T24 cancer cells (high-grade), while weak intensity 4-ATP SERS responses to targets were obtained by grade-I RT4 bladder cancer cells, NIH/3T3 fibroblast cells, and SV-HUC1 bladder normal cells. This SERS nanoprobe platform makes primary bladder carcinoma screening from in vitro to ex vivo more straightforward. Our demonstration offers exciting potential for SERS screening of specific receptors on cancer cells of different grades and facilitates new opportunities ranging from surface engineering of SERS material tags to SERS imaging-guided and targeted phototherapy of cancer cells by controlling the laser powers.

Li-CO2 batteries have recently attracted attention as promising candidates for next-generation energy storage devices due to their extremely high theoretical energy density. The real application of Li-CO2 cells involves addressing several drawbacks, including high charging potential, poor coulombic efficiency, and low rechargeability. Molybdenum disulfide supported on carbon nanotubes (MoS2/CNT) with various ratios functioned as a cathode catalyst for Li-CO2 batteries. The optimal MoS2/CNT composite achieved a maximum discharge capacity of 8551 mAh g-1 with a coulombic efficiency of 96.7%. This hybrid also obtained an initial charging plateau of 3.87 V at a current density of 100 mA g-1 with a cutoff capacity of 500 mAh g-1. It provided ideal electrochemical stability of 142 cycles at the current densities of 100 mA g-1, which was comparable with that of some precious metal catalysts. This optimized MoS2/CNT was also cycled at 200 and 400 mA g-1 for 112 and 55 times, respectively. Density functional theory calculations demonstrated that the sulfided Mo-edge (s-Mo-edge) on MoS2 materials showed appropriate adsorption strengths of Li, CO2, and Li2CO3. Moreover, joint results of Raman profiles and extended X-ray absorption fine structure spectra elucidated that the catalytic efficiencies of MoS2/CNT hybrids were proportional to the quantities of exposed s-Mo-edge active sites.

A double D-shaped optical fiber for simultaneous temperature and relative humidity (RH) sensing is described. The flat surfaces of the D-shaped optical fiber are coated with toluene as a thermally ...

Electrochemical tests were developed to investigate the electrochemical dissolution behavior of gold and its main coexistent sulfide minerals in acid thiocyanate solutions. The optimal leaching conditions for gold in acidic thiocyanate system were pH 2, 0.15 mol·L−1 thiocyanate and 0.2 g·L−1 Fe3+. Fe3+ addition to the acidic thiocyanate system promoted gold dissolution significantly, arsenopyrite dissolution was inhibited, chalcopyrite dissolution was increased, and the dissolution behavior of other associated minerals remained mostly unchanged. Thiocyanate made gold and associated mineral leaching easier. The galvanic corrosion effect of gold and its main coexistent sulfide minerals in an acidic thiocyanate-free system was that the chalcocite, arsenopyrite and pyrite acted as a cathode to reduce anodic gold dissolution; galena as an anode undergoes oxidation to inhibit anodic gold dissolution. There was almost no galvanic corrosion behavior between stibnite, yellow sphalerite and black sphalerite and gold. Thiocyanate addition changed the galvanic corrosion behavior of stibnite and yellow sphalerite in the thiocyanate system, which inhibited anodic gold dissolution. In the acidic thiocyanate system in the presence of ferric iron, the arsenopyrite promoted anodic gold dissolution, the chalcocite and gold were mostly free of galvanic corrosion, and the remaining minerals inhibited anodic gold dissolution.

Engineered nanoparticles raise safety concerns. Silver nanoparticles (AgNPs) exert acute and chronic adverse effects by inducing reactive oxygen species (ROS)-mediated stress signaling pathways. We investigated the mechanisms by which AgNPs exert lasting adverse effects on longevity, as well as their sublethal effects on functional aging. Drosophila was used as a model to systematically study the mechanisms of small AgNP-induced acute and long-term toxicity. We demonstrated that dietary exposure to 12.5 nm AgNPs during early life increases cytotoxicity and animal lethality by strongly inducing ROS production. Early life exposure to AgNPs leads to increased lifetime bioaccumulation later in life and dose-dependent adverse effects on functional aging; e.g., shortened lifespan and loss of stress resistance and intestinal integrity. AgNPs inactivate antioxidant pathways in old, not young, animals, which increase susceptibility to ROS stress. Moreover, pterostilbene (PT), a methoxylated resveratrol, reversed the negative effects of AgNPs on longevity and age-related function by reducing ROS and upregulating antioxidant pathways. Thus, lifetime bioaccumulation of AgNPs accelerates functional aging by inactivating antioxidant pathways and PT reverses these effects. Our findings provide insight into the mechanisms driving the toxicity of bioaccumulated AgNPs and help establish a scientific foundation to guide the safe use of AgNPs.

Tetramethylammonium trifluoromethylselenate ([Me4N][SeCF3]) has been confirmed as an excellent precursor of selenofluorophosgene for amines in the preparation of selenocarbamoyl fluorides, selenoureas, and heterocycles under catalyst- and additive-free conditions. Reactions of [Me4N][SeCF3] with secondary amines at room temperature provided exclusively selenocarbamoyl fluorides in moderate to high yields, while the same reactions with primary amines afforded selenoureas in good yields. When [Me4N][SeCF3] was similarly mixed with amines containing adjacent amino, hydroxyl or thiol groups, five- and six-membered heterocycles were produced. The reaction featured simplicity, rapidness, high efficiency, a broad substrate scope, and good functional group tolerance, offering a convenient access to a variety of selenocarbonylated compounds, which were otherwise difficult to synthesize by other approaches.