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The carcinogenicity of aristolochic acids (AAs) has been attributed mainly to the formation of stable DNA-aristolactam (DNA-AL) adducts by its reactive N -sulfonated metabolite N-sulfonatooxyaristolactam (N–OSO 3 --AL). The most accepted mechanism for such DNA-AL adduct formation is via the postulated but never unequivocally-confirmed aristolactam nitrenium ion. Here we found that both sulfate radical and two ALI-derived radicals (N-centered and C-centered spin isomers) were produced by N–OSO 3 --ALI, which were detected and unequivocally identified by complementary applications of ESR spin-trapping, HPLC-MS coupled with deuterium-exchange methods. Both the formation of the three radical species and DNA-ALI adducts can be significantly inhibited (up to 90%) by several well-known antioxidants, typical radical scavengers, and spin-trapping agents. Taken together, we propose that N–OSO 3 --ALI decomposes mainly via a new N–O bond homolysis rather than the previously proposed heterolysis pathway, yielding reactive sulfate and ALI-derived radicals, which are together and in concert responsible for forming DNA-ALI adducts. This study presents strong and direct evidence for the production of free radical intermediates during N–OSO 3 --ALI decomposition, providing an unprecedented free radical perspective and conceptual breakthrough, which can better explain and understand the molecular mechanism for the formation of DNA-AA adducts, the carcinogenicity of AAs and their potential prevention. [Display omitted] • First direct ESR evidence of aristolochic acid-related aristolactam radical. • Identification of two isomers of aristolactam radical by ESR and HPLC-MS. • First evidence for sulfate radical formation under physiological conditions. • Synergistic free radical mechanism for forming DNA-aristolactam adducts. • First radical mechanism for DNA damage & carcinogenicity by aristolochic acid. [ABSTRACT FROM AUTHOR]

• FRP grid was proposed as reinforcement for 3D printed HPC plates. • Tension and bending tests on both FGPH plates were conducted. • The performance of 3D printed HPC plates under bending and tension is enhanced substantially. • Cast plates had slightly better performance than the printed plates. • The pore structures in HPC were observed and discussed. High-performance concrete (HPC) has become increasing popular in structural engineering. Capitalizing the advanced construction technology of 3D concrete printing (3DCP) and merits of HPC, structures with various profiles could be designed and constructed easily. As the mechanical properties of 3D printed concrete may be worse than the corresponding concrete cast by the conventional technology, this study proposes to evolve flexible fiber-reinforced polymer (FRP) grid as reinforcement for 3D printed HPC plates. Twelve plates were tested to explore the effects of the loading direction and fabrication type on the flexural behavior of FRP grid reinforced HPC plates. The results showed that the performance of the 3D printed HPC plates can be considerably enhanced owning to the FRP grid reinforcement. Additionally, the μCT-scanned images show that the pores between deposition layers were elongated due to the movement of the nozzle during printing, and the pores were stretched in the printing direction. The flexible FRP reinforcement may allow 3D printing of FRP reinforced concrete elements in the future. [ABSTRACT FROM AUTHOR]

Recurrent stroke after revascularization surgeries predicts poor outcome in patients with moyamoya disease (MMD). Early identification of patients with stroke risk paves the way for rescue intervention. This study aimed to investigate the role of ultrasound in identifying patients at risk of post-operative ischemic events (PIEs). This prospective study enrolled patients with symptomatic MMD who underwent indirect revascularization surgeries. Ultrasound examinations were performed preoperatively and at 3 mo post-operatively to evaluate the hemodynamic changes in extracranial and intracranial arteries on the operated side. PIE was defined as ischemic stroke or transient ischemic attack in the operated hemisphere within 1 y. The areas under receiver operating characteristic curves were compared between models for prediction of PIE. A total of 56 operated hemispheres from 36 patients (mean age, 23.0 ± 18.5 y) were enrolled in this study, and 27% developed PIE. In multivariate logistic regression models, PIE was associated with lower end-diastolic velocity and flow volume (FV) of the ipsilateral external carotid artery (ECA), and lower FV of ipsilateral superficial temporal artery and occipital artery at 3 mo post-operatively (all p < 0.05). Moreover, the post-operative FV of the ipsilateral ECA was the only one factor that significantly increased the areas under receiver operating characteristic curves from 0.727 to 0.932 when adding to a clinical–angiographic model for prediction of PIE (p = 0.017). This parameter was significantly lower in hemispheres with PIE, both in adult and pediatric patients. After indirect revascularization, surgeries in patients with symptomatic MMD, FV of ipsilateral ECA at 3 mo helps clinicians to identify patients at risk of PIE. [ABSTRACT FROM AUTHOR]

Acetylhydrazine (AcHZ), a major human metabolite of the widely-used anti-tuberculosis drug isoniazid (INH), was considered to be responsible for its serious hepatotoxicity and potentially fatal liver injury. It has been proposed that reactive radical species produced from further metabolic activation of AcHZ might be responsible for its hepatotoxicity. However, the exact nature of such radical species remains not clear. Through complementary applications of ESR spin-trapping and HPLC/MS methods, here we show that the initial N-centered radical intermediate can be detected and identified from AcHZ activated by transition metal ions (Mn(III)Acetate and Mn(III) pyrophosphate) and myeloperoxidase. The exact location of the radical was found to be at the distal-nitrogen of the hydrazine group by 15N-isotope-labeling techniques via using 15N-labeled AcHZ we synthesized. Additionally, the secondary C-centered radical was identified unequivocally as the reactive acetyl radical by complementary applications of ESR spin-trapping and persistent radical TEMPO trapping coupled with HPLC/MS analysis. This study represents the first detection and unequivocal identification of the initial N-centered radical and its exact location, as well as the reactive secondary acetyl radical. These findings should provide new perspectives on the molecular mechanism of AcHZ activation, which may have potential biomedical and toxicological significance for future research on the mechanism of INH-induced hepatotoxicity. [Display omitted] • N-centered radical of AcHZ was identified by both ESR and HPLC/MS methods. • N-centered radical was identified on the distal-N by 15N-labeled technique. • The adduct of acetyl radical with biomolecules was identified by HPLC/MS. [ABSTRACT FROM AUTHOR]

Phytochemical study on the whole plant Lagopsis supina led to the isolation of twenty-nine compounds, which consist of five triterpenoids (1 – 5), six steroids (6 – 11), three phenylpropanoids (12 – 14), two flavonoids (15 – 16), five fatty acid derivatives (17 – 21), one dipeptide (22), one sesquiterpenoid (23), and six phenols (24 – 29). Their structures were elucidated based on analysis of spectroscopic data and comparison with literature data. In this work, compounds 1 – 3 , 12 – 14 , 19 , 21 , and 24 are reported from the Lamiaceae family for the first time, while all compounds except 5 , 9 and 15 are reported from the Lagopsis genus for the first time. Compounds 17 , 18 and 20 were previously obtained through synthetic methods only, and are therefore discovered as natural products for the first time. Moreover, the chemotaxonomic significance of the isolated compounds is discussed. • Twenty-nine compounds were isolated from Lagopsis supina. • Twenty-six compounds are reported from Lagopsis for the first time. • Nine compounds are reported from Lamiaceae for the first time. • Chemotaxonomic relationships of these isolates are discussed. [ABSTRACT FROM AUTHOR]

Organic thermoelectric fibers (OTEFs) are popular in wearable self-powered technology due to easy weaving and power generation. However, limitations include poor spinning capability, weak mechanical strength, low output power, and dangerous post-treatment. Here, we report the rapid preparation of flexible, high-performance OTEFs without post-treatment through introducing ionic liquid (IL) of 1-ethyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide (EMIM: TFSI) into the Poly (3,4-ethylene dioxythiophene): Poly (styrene sulfonate) (PEDOT: PSS) to enhance thermoelectric properties, and mechanical strength, with just 1 wt% of IL enabling continuous fabrication of the PEDOT: PSS fiber. The resulting fiber exhibits remarkable electrical, and thermoelectric performance of ∼2267.7 S cm−1, and ∼85 μW m−1 K−2, respectively. It also demonstrates excellent strength (∼289.72 MPa), with a resistance change of less than 8 % after 10,000 bending cycles. The fabricated five-legs devices achieve an impressive output power and output power density of ∼7.84 nW and ∼4.32 μW cm−2 at 49 K, and the fabric textile generates a significant voltage of ∼47.8 mV using human body heat. This work proposes a new design strategy for high-performance organic thermoelectric fibers without additional post-processing, and the ultra-high output power and flexibility exhibit excellent combined application potential in both organic and inorganic TE fields. Ion-induced phase separation and the construction of physical micro-crosslinking spots encourage the thermoelectric and mechanical performance of PEDOT: PSS fiber. [Display omitted] • A simple method for the continuous preparation of efficient OTEFs without requiring post-treatment is proposed. • Ion-induced phase separation and physical micro-crosslinking sites facilitated conductive and mechanical performance. • PEDOT: PSS fiber exhibits remarkable electrical, and thermoelectric performance compared with other thermoelectric fibers. • The fabricated devices achieve an excellent output power density. [ABSTRACT FROM AUTHOR]

We have shown previously that exposing bacteria to tetrachlorocatechol (TCC) and sodium azide (NaN 3) together causes synergistic cytotoxicity in a biphasic mode. However, the underlying chemical mechanism remains unclear. In this study, an unexpected ring-contraction 3(2 H)-furanone and two quinoid-compounds were identified as the major and minor reaction products, respectively; and two unusual azido-substituted chloro- O -semiquinone radicals were detected and characterized as the major radical intermediates by complementary applications of direct ESR, HPLC/ESI-Q-TOF and high-resolution MS studies with nitrogen-15 isotope-labeled NaN 3. Taken together, we proposed a novel molecular mechanism for the reaction of TCC/NaN 3 : N 3 - may attack on tetrachloro- O -semiquinone radical, forming two transient 4-azido-3,5,6-trichloro- and 4,5-diazido-3,6-dichloro- O -semiquinone radicals, consecutively. The second-radical intermediate may either undergo an unusual zwitt-azido cleavage to form the less-toxic ring-contraction 3(2 H)-furanone product, or further oxidize to form the more toxic quinoid-product 4-amino-5-azido-3,6-dichloro- O -benzoquinone. A good correlation was observed between the biphasic formation of this toxic quinone due to the two competing decomposition pathways of the radical intermediate and the biphasic synergism between TCC and NaN 3 , which are dependent on their molar-ratios. This is the first report of detection and identification of two unique azido-substituted chloro- O -semiquinone radicals, and an unprecedented ring-contraction mechanism via an unusually mild and facile zwitt-azido rearrangement. [Display omitted] • Two azido-substituted chloro- O -semiquinone radicals were separated and identified. • The ring-contraction 3(2H)-furanone was the major product in TCC/NaN 3 reaction. • The major pathway for TCC/NaN 3 is an unusual mild and facile zwitt-azido rearrangement. • Both radical VII and quinoid II are responsible for the TCC/NaN 3 lethal synergism. • The halocatechol/azide reaction may be used as a new method to synthesize 3(2H)-furanones. [ABSTRACT FROM AUTHOR]

3D printed concrete has become increasing popular in research and industry communities, while it faces a lack of effective internal reinforcement. Fiber-reinforced polymer (FRP) reinforcement, which has been used widely as reinforcement for concrete structures, has also been adopted to enhance the performance of 3D printed concrete structures. However, conventional FRP manufacturing processes such as pultrusion does not allow on-site forming of the products, leading to difficulties in construction. This paper aims to solve the above issues by developing a novel form of 3D printed continuous fiber reinforced thermoplastic polymers (CFRTPs) reinforcement for 3D printed concrete structures. An experimental program on tensile behavior of 3D printed CFRTP bars and grids was conducted. Then the CFRTP reinforcement was used for 3D printed high-performance concrete to explore the effectiveness of the reinforcement. Twenty-two 3D printed concrete plates were tested to explore the effects of the loading direction and fabrication type on the flexural behavior of FRP reinforced high-performance concrete plates. Results show that the performance of the 3D printed HPC plates can be considerably enhanced owning to the FRP reinforcement and the CFRTP reinforcement are comparable to conventional FRP reinforcement with similar dimensions. This study identifies further research needs on CFRTP reinforcement for construction and will pave the way for studies on 3D printed reinforced concrete structures with both concrete and FRP reinforcement being printed simultaneously. [ABSTRACT FROM AUTHOR]

We found recently that benzohydroxamic acid (BHA) could detoxify the chlorinated quinoid carcinogens via an unusual Lossen rearrangement reaction. However, it is not clear what would happen when the nitrogen hydrogen of BHA was substituted with methyl and other alkyl groups. Here we show that N -methyl benzohydroxamic acid (N -MeBHA, a simple model compound for the classic iron-chelator deferoxamine, which is a typical N -alkyl trihydroxamic acid) could react with 2,5-dichloro-1,4-benzoquinone (DCBQ) to form a relatively stable initial carbon-oxygen bonding conjugation intermediate CBQ-O- N -MeBHA. However, the major final product was identified, unexpectedly, as a carbon-nitrogen bonding conjugate CBQ(OH)–N(CH 3)-COAr, which is the rearranged isomer of CBQ-O- N -MeBHA. Interestingly, a new 18-line nitrogen-centered radical and a carbon-centered quinone ketoxy radical were observed by the ESR spin-trapping method, which was further confirmed by HPLC-MS and 15N-isotope labeling methods. We further found that both new DNA adducts and DNA strand breaks could be produced by the reactive nitrogen-centered radical. Taken together, we propose that the reaction between DCBQ and N -MeBHA was not via the Lossen rearrangement, but rather through a novel radical homolysis and recoupling pathway. Analogous results were observed for other chlorinated quinones and N -alkyl hydroxamic acids including the widely-used trihydroxamate iron-chelating drug deferoxamine. This represents the first report of unexpected radical pathway for the reaction between chlorinated quinones and N -alkyl hydroxamic acids under normal physiological conditions, which may have broad biological and environmental significance for future study of carcinogenic chloroquinones and hydroxamic acid drugs. Image 1 • Reactive N -centered radicals can be produced from N -alkyl hydroxamic acids & chloroquinones. • N -centered radicals were identified by ESR, HPLC-MS and 15N-isotope labeling methods. • A C–N bonding conjugate was the major reaction product between dichloroquinone and N -MeBHA. • DNA adducts & DNA strand breaks could be induced by the reactive N -centered radical. • The reaction mechanism for chloroquinones/ N -alkyl hydroxamic acids is a radical rearrangement. [ABSTRACT FROM AUTHOR]

Eight previously unreported sesquiterpene coumarins, namely (+)- and (−)-ferulasinkian A (1), (−)-fukanefuromarin M (2), (±)-ferulasinkian C (3), (±)-ferulasinkian D (4), ferulasinkian E (5), ferulasinkian F (7), and ferulasinkian G (8), together with two known compounds, (+)-fukanefuromarin M (2) and 7-hydroxyferprenin (6), have been isolated from the roots of Ferula sinkiangensis (Umbelliferae). The structures of all compounds were elucidated by spectroscopic analysis, along with ECD calculations and optical rotation calculations. Compounds 1 – 6 are dimers consisting of a chain sesquiterpene and a coumarin with an oxygen-containing six-membered ring connected from coumarin C-3 and C-4. Currently, there are only seven such structures reported in the genus Ferula , and their absolute configurations have not yet been determined. Compounds 7 – 8 are sesquiterpene coumarin derivatives with a chain sesquiterpene connected with coumarin C-4. In the present study, the chiral separation of compounds (±)- 1 and (±)- 2 was successfully carried out, and the absolute configurations of compounds (±)- 1 , (±)- 2 , 5 , 7 and 8 were determined. The isolates were evaluated for their cytotoxic activity against human pancreatic cancer cell lines including CFPAC-1, PANC-1, CAPAN-2 and SW 1990. Compounds (+)- 1 , (−)- 1 and 7 exhibited potent cytotoxicity against pancreatic cancer cells with IC 50 values ranging from 4.57 ± 0.94 to 14.01 ± 1.03 μM. Furthermore, the primary mechanistic study of (−)- 1 demonstrated that it could induce apoptosis in CFPAC-1 cells. Eight previously unreported and two known sesquiterpene coumarins were isolated from the roots of Ferula sinkiangensis. Compounds (−)- 1 , (+)- 1 and 7 exhibited potent cytotoxicity against pancreatic cancer cells with IC 50 values ranging from 4.57 ± 0.94 to 14.01 ± 1.03 μM. [Display omitted] • Eight previously unreported and two known sesquiterpene coumarins were isolated from the roots of the F. sinkiangensis. • The chiral separation of compounds (±)- 1 and (±)- 2 were successfully carried out. • The absolute configurations of compounds (±)- 1 , (±)- 2 , 5 , 7 and 8 were determined. • Compounds (−)- 1 , (+)- 1 and 7 exhibited potent cytotoxicity against pancreatic cancer cells with IC 50 values ranging from 4.57 ± 0.94 to 14.01 ± 1.03 μM. [ABSTRACT FROM AUTHOR]