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The objective of this study is to analytically determine the effectiveness of a novel bridge system with superelastic (SE) shape memory alloy (SMA) reinforced concrete piers. The bridge is also equipped with SE SMA cable restrainers to prevent the bridge spans from a large displacement that can potentially cause span unseating. In the concrete bridge piers, the conventional steel reinforcements in the plastic hinge regions are replaced with SE SMA rebar to avoid large plastic deformation and improve its self‐centering capacity. A typical three‐span continuous highway bridge is modeled with SMA‐reinforced piers and SMA restrainers. Numerical simulations of the bridge are conducted under destructive near‐fault ground motions. The seismic responses and fragility curves of the novel bridge (Bridge IV) are assessed and compared with the reference bridge (Bridge I), the bridge with only SMA‐reinforced piers (Bridge II), and the bridge with only SMA restrainers (Bridge III). The results revealed that the SMA‐reinforced pier can successfully reduce the residual deformation and damage probability of the bridge; however, the bridge with only SMA‐reinforced piers is less efficient in preventing a large displacement. The use of SMA restrainers can efficiently limit the displacement of the bridge spans but increase the damage probability of the bridge piers. The proposed novel bridge having SMA‐reinforced piers equipped with SMA restrainers (Bridge IV) is more efficient than the bridge with only SMA‐reinforced piers (Bridge II)) or the bridge with only SMA restrainers (Bridge III). [ABSTRACT FROM AUTHOR]

To explore the effects of biogas slurry coordinating chemical fertilizer on growth promotion of tomato, we used three kinds of typical biogas slurry as concentrated nutrient solution, respectively fermented from raw duck manure, pig manure, cow dung, while urea, monocalcium phosphate and potassium sulphate as auxiliary nutrition to balance the nutrient difference between different dilution ratios of biogas slurry. The results showed the biogas slurry partially substituting chemical fertilizer could significantly improve soil fertility, including available nitrogen, phosphorus, and potassium. As for water soluble calcium, magnesium, iron, manganese and zinc in soil, biogas slurry application could activate their availability, with the magnitude of such effects depended on the fermentation level of raw materials and dilution ratio. Compared with chemical fertilizer, coordinating biogas liquid fertilizer significantly promoted the growth of tomato, with the yield increased by 55.9%-.8% and the chemical fertilizer dosage decreased by 8.% -85.0%. Furthermore, such effects became more prominent along with prolonged time. The fruit quality was sig-nificantly improved with the increases of lycopene, ascorbic acid and total sugar, and the decreases of acidity and nitrite concentration, and the decrease of NO2 by 5.6%-90.%. In addition, the taste flavor of fruits was 7.0%-0.% higher than that of chemical fertilizer treatment. The yield and quality of tomato took on nonlinear synchronization, and the relation between taste flavor and sugar/acid showed significantly positive correlation, which was affected by fertilizer type. Biogas slurry partly substituting chemical fertilizer could achieve the goals of high yield, high quality, environmental protection, efficient utilization of agricultural resources in tomato production. [ABSTRACT FROM AUTHOR]

This article investigates the efficiency of a new generation smart isolation system, namely shape memory alloy wire-based lead rubber bearing, for the seismic response control of long-span cable-stayed bridge systems under near-fault ground motions. The constitutive model of shape memory alloy wire-based lead rubber bearings is coded and implemented into OpenSees as a new user element. This user element can accurately predict the re-centering capability and energy dissipation capacity of shape memory alloy wire-based lead rubber bearing under different excitations. The Sutong cable-stayed bridge in China, with a main span of 1088 m, is taken as an example. Results reveal that implementing shape memory alloy wires into lead rubber bearings can effectively increase the self-centering property and, as a result, reduce the residual deformation in shape memory alloy wire-based lead rubber bearings under near-fault ground motions. Shape memory alloy wires lead to an increase in the horizontal stiffness and energy dissipation capacity of shape memory alloy wire-based lead rubber bearings. The deck displacement is restricted effectively, and a superior structural performance is achieved in terms of the deck acceleration. Shape memory alloy wire-based lead rubber bearings can effectively reduce the base shear and base moment of the towers. However, it is observed that an increase in the shape memory alloy wire diameter may have negligible effect on the deck acceleration, tower base shear and moment, and in some cases, on the pier base shear and moment. [ABSTRACT FROM AUTHOR]

The ADDSYM routine in the program PLATON [Spek (2015). Acta Cryst. C 71, 9-18] has helped researchers to avoid structures of (metal-)organic compounds being reported in an unnecessarily low symmetry space group. However, determination of the correct space group may get more complicated in cases of pseudosymmetric inorganic compounds. One example is NaVO2F2, which was reported [Crosnier-Lopez et al. (1994). Eur. J. Solid State Inorg. Chem. 31, 957-965] in the acentric space group P21 based on properties but flagged by ADDSYM as (pseudo)centrosymmetric P21/ m within default distance tolerances. Herein a systematic investigation reveals that NaVO2F2 exists in at least four polymorphs: P21, (I), P21/ m, (II), P21/ c, (III), and one or more low-temperature ones. The new centrosymmetric modification, (III), with the space group P21/ c has a similar atomic packing geometry to phase (I), except for having a doubled c axis. The double-cell of phase (III) arises from atomic shifts from the glide plane c at ( x, , z). With increasing temperature, the number of observed reflections decreases. The odd l reflections gradually become weaker and, correspondingly, all atoms shift towards the glide plane, resulting in a gradual second-order transformation of (III) into high-temperature phase (II) ( P21/ m) at below 493 K. At least one first-order enantiotropic phase transition was observed below 139 K from both the single-crystal X-ray diffraction and the differential scanning calorimetry analyses. Periodic first-principles calculations within density functional theory show that both P21/ c superstructure (III) and P21 substructure (I) are more stable than P21/ m structure (II), and that P21/ c superstructure (III) is more stable that P21 substructure (I). [ABSTRACT FROM AUTHOR]

A novel, mixed- and high-valence manganese (Mn3+/Mn4+) fluorophosphate, MnIII6F12(PO3(OH))8[Na8(Kx(H3O)4−x(H2O)2)MnIV(OH)6] (denoted as MN), has been prepared via a water-deficient hydrothermal route with phosphoric acid as the sole solvent. This compound features a cubic three-dimensional open-framework structure built from corner-sharing [MnIIIO4F2] octahedra and [HPO4] groups, which encapsulates a clathrate-like “guest cluster” of Na8(Kx(H3O)4−x(H2O)2)MnIV(OH)6. The guest cluster is architecturally composed of a [MnIV(OH)6] octahedron in a cubic cage of Na+ cations, which in turn is surrounded by an octahedral arrangement of K+/H2O ions, resulting in an unprecedented octahedral @ cubic @ octahedral @ cubic arrangement (OCOC). The +4 oxidation state of Mn in the guest cluster has been confirmed by the synthesis of isotypic Ti- and Ge- analogues (denoted as TI and GE) using TiO2 and GeO2 as the replacement for MnO2 in the starting materials. The compounds MN, TI and GE are not stable in aqueous solution and are peeled off layer-by-layer after the absorption of water. This report provides a new route for the synthesis of mixed- and high-valence manganese phosphates that cannot be produced by conventional hydrothermal methods. [ABSTRACT FROM AUTHOR]

An analytical method was developed to study the wave diffraction effects on V-type bottom-mounted breakwaters. The breakwater is assumed to be rigid, thin, impermeable and located in water of constant depth. The fluid domain is divided into three regions by an imaginary interface. The velocity potential in each region is expanded by eigenfunctions. By satisfying continuity of pressure and normal velocity across the imaginary fluid interface, a set of linear algebraic equations can be obtained to determine the unknown coefficients for eigenfunctions. The accuracy of the present model is verified by a comparison with existing results for the case of an isolated breakwater. Numerical results, in the form of contour maps of the relative wave amplitude around the breakwater, were presented for a range of wave and breakwater parameters. The results show the V-type bottom-mounted breakwater is generally effective in defending against waves. In general, the wave height in the protected area is about 20% ~50% of incident wave height. [ABSTRACT FROM AUTHOR]

Overexpression of ATP-binding cassette (ABC) transporters is one of the most important mechanisms responsible for the development of multidrug resistance (MDR). Selonsertib, a serine/threonine kinase inhibitor, targets apoptosis signal-regulating kinase 1 (ASK1) and is now in phase III clinical trial for the treatment of non-alcoholic steatohepatitis (NASH). In this study, we investigated whether selonsertib could reverse MDR-mediated by ABC transporters, including ABCB1, ABCG2, ABCC1 and ABCC10. The results showed that selonsertib significantly reversed ABCB1- and ABCG2-mediated MDR, but not MDR-mediated by ABCC1 or ABCC10. Mechanism studies indicated that the reversal effect of selonsertib was related to the attenuation of the efflux activity of ABCB1 and ABCG2 transporters, without the protein level decrease or change in the subcellular localization of ABCB1 or ABCG2. Selonsertib stimulated the ATPase activity of ABCB1 and ABCG2 in a concentration-dependent manner, and in silico docking study showed selonsertib could interact with the substrate-binding sites of both ABCB1 and ABCG2. This study provides a clue into a novel treatment strategy, which includes a combination of selonsertib with antineoplastic drugs to attenuate MDR-mediated by ABCB1 or ABCG2 in cancer cells overexpressing these transporters. [ABSTRACT FROM AUTHOR]

Overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1 and ABCG2, strongly correlates with multidrug resistance (MDR), rendering cancer chemotherapy ineffective. Exploration and identification of novel inhibitors targeting ABCB1 and ABCG2 are necessary to overcome the related MDR. Mobocertinib is an approved EGFR/HER2 inhibitor for non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations. This study demonstrates that mobocertinib can potentially reverse ABCB1- and ABCG2-mediated MDR. Our findings indicate a strong interaction between mobocertinib and these two proteins, supported by its high binding affinity with ABCB1 and ABCG2 models. Through inhibiting the drug efflux function of ABCB1 and ABCG2, mobocertinib facilitates substrate drugs accumulation, thereby re-sensitizing substrate drugs in drug-resistant cancer cells. Additionally, mobocertinib inhibited the ATPase activity of ABCB1 and ABCG2 without changing the expression levels or subcellular localization. In the tumor-bearing mouse model, mobocertinib boosted the antitumor effect of paclitaxel and topotecan, resulting in tumor regression. In summary, our study uncovers a novel potential for repurposing mobocertinib as a dual inhibitor of ABCB1 and ABCG2, and suggests the combination of mobocertinib with substrate drugs as a strategy to counteract MDR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Zhe-Sheng Chen is an editorial board member of Cancer Letters., (Copyright © 2024. Published by Elsevier B.V.)

The therapeutic effect of chemotherapy and targeted therapy are known to be limited by drug resistance. Substantial evidence has shown that ATP-binding cassette (ABC) transporters P-gp and BCRP are significant contributors to multidrug resistance (MDR) in cancer cells. In this study, we demonstrated that a clinical-staged ATR inhibitor ceralasertib is susceptible to P-gp and BCRP-mediated MDR. The drug resistant cancer cells were less sensitive to ceralasertib compared to the parental cells. Moreover, ceralasertib resistance can be reversed by inhibiting the drug efflux activity of P-gp and BCRP. Interestingly, ceralasertib was able to downregulate the level of P-gp but not BCRP, suggesting a potential regulation between ATR signaling and P-gp expression. Furthermore, computational docking analysis predicted high affinities between ceralasertib and the drug-binding sites of P-gp and BCRP. In summary, overexpression of P-gp and BCRP are sufficient to confer cancer cells resistance to ceralasertib, underscoring their role as biomarkers for therapeutic efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Chen, Wu, Wang, Teng, Tang, Liu, Chen and Chen.)

On January 25, 2022, the U.S. Food and Drug Administration (FDA) approved the use of tebentafusp, a bispecific glycoprotein 100 (gp100) peptide-human leukocyte antigen (HLA)-directed CD3 T-cell activator, for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM). Pharmacodynamic data indicate that tebentafusp targets a specific HLA-A*02:01/gp100 complex, activating both CD4+/CD8+ effector and memory T cells that induce tumor cell death. Tebentafusp is administered to patients via intravenous infusion daily or weekly, depending on the indication. Phase III trials have documented a 1-year overall survival of 73%, overall response rate of 9%, progression-free survival of 31% and disease control rate of 46%. Common adverse events reported are cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache and vomiting. Compared to other types of melanomas, mUM presents with a distinct profile of genetic mutations, which phenotypically results in limited survival efficacy when using traditional melanoma treatments. The low current treatment efficacy for mUM, alongside a poor long-term prognosis and high mortality rates, gives precedence for the approval of tebentafusp to be groundbreaking in its clinical impact. This review will discuss the pharmacodynamic and pharmacokinetic profile, and the clinical trials used to evaluate the safety and efficacy of tebentafusp., (Copyright 2023 Clarivate.)

The U.S. Food and Drug Administration (FDA) first approved amivantamab, a monoclonal epidermal growth factor receptor (EGFR)-mesenchymal--epithelial transition factor (MET) bispecific antibody, in May 2021, to treat adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with an insertion mutation in exon 20 of EGFR. The approval of amivantamab represents a targeted therapy for this subtype of advanced NSCLC. In contrast to other drugs that inhibit the tyrosine kinase activity in the protein, EGFR, amivantamab has efficacy in inhibiting EGFR and MET. In this article, we summarize the development of therapeutic drugs for NSCLC, discuss the mechanism of action of amivantamab, review data from clinical trials with amivantamab and suggest future lines of research., (Copyright 2022 Clarivate.)

Ko143, a potent ABCG2 inhibitor that reverses multidrug resistance in cancer, cannot be used clinically due to its unsuitable metabolic stability. We identified benzoyl indoles as reversal agents that reversed ABCG2-mediated multidrug resistance (MDR), with synthetic tractability and enhanced metabolic stability compared to Ko143. Bisbenzoyl indole 2 and monobenzoyl indole 8 significantly increased the accumulation of mitoxantrone (MX) in ABCG2-overexpressing NCI-H460/MX20 cells, and sensitized NCI-H460/MX20 cells to mitoxantrone. Mechanistic studies were conducted by [ 3 H]-MX accumulation assay, Western blot analysis, immunofluorescence analysis and ABCG2 ATPase assay. The results revealed that the reversal efficacies of compounds 2 and 8 were not due to an alteration in the expression level or localization of ABCG2 in ABCG2-overexpressing cell lines. Instead, compounds 2 and 8 significantly stimulated the ATP hydrolysis of ABCG2 transporter, suggesting that these compounds could be competitive substrates of ABCG2 transporter. Overall, the results of our study indicated that compounds 2 and 8 significantly reversed ABCG2-mediated MDR by blocking the efflux of anticancer drugs., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

To explore the effects of biogas slurry coordinating chemical fertilizer on growth promotion of tomato, we used three kinds of typical biogas slurry as concentrated nutrient solution, respectively fermented from raw duck manure, pig manure, cow dung, while urea, monocalcium phosphate and potassium sulphate as auxiliary nutrition to balance the nutrient difference between different dilution ratios of biogas slurry. The results showed the biogas slurry partially substituting chemical fertilizer could significantly improve soil fertility, including available nitrogen, phospho-rus, and potassium. As for water soluble calcium, magnesium, iron, manganese and zinc in soil, biogas slurry application could activate their availability, with the magnitude of such effects depended on the fermentation level of raw materials and dilution ratio. Compared with chemical fertilizer, coordinating biogas liquid fertilizer significantly promoted the growth of tomato, with the yield increased by 55.9%-232.8% and the chemical fertilizer dosage decreased by 18.2%-85.0%. Furthermore, such effects became more prominent along with prolonged time. The fruit quality was significantly improved with the increases of lycopene, ascorbic acid and total sugar, and the decreases of acidity and nitrite concentration, and the decrease of NO 2 - by 35.6%-90.3%. In addition, the taste flavor of fruits was 7.0%-20.3% higher than that of chemical fertilizer treatment. The yield and quality of tomato took on nonlinear synchronization, and the relation between taste flavor and sugar/acid showed significantly positive correlation, which was affected by fertilizer type. Biogas slurry partly substituting chemical fertilizer could achieve the goals of high yield, high quality, environmental protection, efficient utilization of agricultural resources in tomato production.

The successful treatment of cancer has significantly improved as a result of targeted therapy and immunotherapy. However, during chemotherapy, cancer cells evolve and can acquire "multidrug resistance" (MDR), which significantly limits the efficacy of cancer treatment and impacts patient survival and quality of life. Among the approaches to reverse MDR, modulating reactive oxidative species (ROS) may represent a strategy to kill MDR cancer cells that are mechanistically diverse. ROS in cancer cells play a central role in regulating and inducing apoptosis, thereby modulating cancer cells proliferation, survival and drug resistance. The levels of ROS and the activity of scavenging/anti-oxidant enzymes in drug resistant cancer cells are typically increased compared to non-MDR cancer and normal cells. Consequently, MDR cancer cells may be more susceptible to alterations in ROS levels. Numerous studies suggest that compounds modulating cellular ROS levels can enhance MDR cancer cell death and sensitize MDR cancer cells to certain chemotherapeutic drugs. In the current review, we discuss the critical and targetable redox-regulating enzymes, including mitochondrial electron transport chain (ETC) complexes, NADPH oxidases (NOXs), enzymes related to glutathione metabolism, glutamate/cystine antiporter xCT, thioredoxin reductases (TrxRs), nuclear factor erythroid 2-related factor 2 (Nrf2), and their roles in regulating cellular ROS levels, drug resistance as well as their clinical significance. We also discuss and summarize the findings in the past decade regarding the efficacy of ROS modulators for the treatment of MDR cancer alone or as sensitizing compounds. Compounds that are efficacious in modulating ROS generation represent a prominent class of drug candidates that warrants evaluation in clinical trials for patients harboring MDR cancers., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The ADDSYM routine in the program PLATON [Spek (2015). Acta Cryst. C71, 9-18] has helped researchers to avoid structures of (metal-)organic compounds being reported in an unnecessarily low symmetry space group. However, determination of the correct space group may get more complicated in cases of pseudosymmetric inorganic compounds. One example is NaVO2F2, which was reported [Crosnier-Lopez et al. (1994). Eur. J. Solid State Inorg. Chem. 31, 957-965] in the acentric space group P2₁ based on properties but flagged by ADDSYM as (pseudo)centrosymmetric P2₁/m within default distance tolerances. Herein a systematic investigation reveals that NaVO2F2 exists in at least four polymorphs: P2₁, (I), P2₁/m, (II), P2₁/c, (III), and one or more low-temperature ones. The new centrosymmetric modification, (III), with the space group P2₁/c has a similar atomic packing geometry to phase (I), except for having a doubled c axis. The double-cell of phase (III) arises from atomic shifts from the glide plane c at (x, ¼, z). With increasing temperature, the number of observed reflections decreases. The odd l reflections gradually become weaker and, correspondingly, all atoms shift towards the glide plane, resulting in a gradual second-order transformation of (III) into high-temperature phase (II) (P2₁/m) at below 493 K. At least one first-order enantiotropic phase transition was observed below 139 K from both the single-crystal X-ray diffraction and the differential scanning calorimetry analyses. Periodic first-principles calculations within density functional theory show that both P2₁/c superstructure (III) and P2₁ substructure (I) are more stable than P2₁/m structure (II), and that P2₁/c superstructure (III) is more stable that P2₁ substructure (I).

A novel, mixed- and high-valence manganese (Mn(3+)/Mn(4+)) fluorophosphate, Mn(III)6F12(PO3(OH))8[Na8(Kx(H3O)4-x(H2O)2)Mn(IV)(OH)6] (denoted as MN), has been prepared via a water-deficient hydrothermal route with phosphoric acid as the sole solvent. This compound features a cubic three-dimensional open-framework structure built from corner-sharing [Mn(III)O4F2] octahedra and [HPO4] groups, which encapsulates a clathrate-like "guest cluster" of Na8(Kx(H3O)4-x(H2O)2)Mn(IV)(OH)6. The guest cluster is architecturally composed of a [Mn(IV)(OH)6] octahedron in a cubic cage of Na(+) cations, which in turn is surrounded by an octahedral arrangement of K(+)/H2O ions, resulting in an unprecedented octahedral @ cubic @ octahedral @ cubic arrangement (OCOC). The +4 oxidation state of Mn in the guest cluster has been confirmed by the synthesis of isotypic Ti- and Ge- analogues (denoted as TI and GE) using TiO2 and GeO2 as the replacement for MnO2 in the starting materials. The compounds MN, TI and GE are not stable in aqueous solution and are peeled off layer-by-layer after the absorption of water. This report provides a new route for the synthesis of mixed- and high-valence manganese phosphates that cannot be produced by conventional hydrothermal methods.

Aim: To examine the effects of pHi on [Ca2+]i, cell length and Ca2+ sensitivity of myofilaments in rat myocyte., Methods: We used microscopic spectral imaging approach to monitor simultaneously [Ca2+]i, pHi and cell length with fluorescent indicator indo-1 and SNARF-1 in isolated single rat myocyte., Results: Exposure of cell to 20 mmol/L Sodium Propionate induced an intracellular acidosis which increased slightly systolic and diastolic [Ca2+]i, decreased the cell shortening (CS) and Ca2+ sensitivity of myofilament (P < 0.01). Exposure of cell to 15 mmol/L NH4Cl induced an intracellular alkalosis which decreased systolic and diastolic [Ca2+]i, increased the cell shortening and Ca2+ sensitivity of myofilament (P < 0.01)., Conclusions: In the early time of acidosis, [Ca2+]i, as well as cell length increases respectively. While alkalosis, [Ca2+]i and cell length decreases respectively. The effect of acidosis and alkalosis on Ca2+ sensitivity presents non-linear relationship, i.e. the effect of acidosis on sensitivity, caused by pHi change, is less than that of alkalosis.