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This study examines the effect of managerial ability on the market valuation of unrecognized tax benefits (UTBs). While UTBs are generally associated with significant risks, we hypothesize that highly able managers can enhance the market valuation of the UTBs through their ability and efforts to report high-quality UTBs and retain the economic benefits of tax strategies. Consistent with our expectations, we find that managerial ability positively moderates the relationship between UTBs and firm values. Our additional analyses show that highly able executives can reduce firms’ future overall tax risk and tax settlements. Collectively, our findings suggest that the stock market values UTBs positively in firms managed by highly capable executives who can minimize tax risks while lowering tax payments.

Abstract Aberrant tumor mechanical microenvironment (TMME), featured with overactivated cancer‐associated fibroblasts (CAFs) and excessive extracellular matrix (ECM), severely restricts penetration and accumulation of cancer nanomedicines, while mild‐hyperthermia photothermal therapy (mild‐PTT) has been developed to modulate TMME. However, photothermal agents also encounter the barriers established by TMME, manifesting in limited penetration and heterogeneous distribution across tumor tissues and ending with attenuated efficiency in TMME regulation. Herein, it is leveraged indocyanine green (ICG)‐loaded soft nanogels with outstanding deformability, for efficient tumor penetration and uniform distribution, in combination with mild‐PTT to achieve potent TMME regulation by inhibiting CAFs and degrading ECM. As a result, doxorubicin (DOX)‐loaded stiff nanogels gain greater benefits in tumor penetration and antitumor efficacy than soft counterparts from softness‐mediated mild‐PTT. This study reveals the crucial role of nanomedicine mechanical properties in tumor distribution and provides a novel strategy for overcoming the barriers of solid tumors with soft deformable nanogels.

Designing ultrathick and hierarchical electrodes is effective to deal with the challenge of high areal capacity and high power density for lithium-ion batteries (LIBs) manufacturing. Here, a thick electrode with hierarchical porous and multidimensional conductive network is fabricated by 3D printing technology, in which both the conducting polymer of poly(3,4-ethylene dioxythiophene):polystyrene sulfonate (PEDOT:PSS) and graphene oxide (GO) play the dual roles as binders and conductive agents. As a consequence, the 3D-printed thick electrode (∼900 μm) with a mass loading of ∼47 mg/cm2 exhibits a good rate capability of 122 mA·h/g at 2 C, a high areal capacity of up to 5.8 mA·h/cm2, and stable cycling performance of ∼95% capacity retention after 100 cycles. Moreover, the C-O-S bond is further confirmed by the spectral analysis and the DFT calculation, which not only hinders the stack of nanosheets but enhances the mechanical stability and electronic conductivity of electrodes. A stable covalent multidimensional conductive network constructed by 3D-printing technology provides a new design strategy to improve the performance of LIBs.

Cuproptosis-based cancer nanomedicine has received widespread attention recently. However, cuproptosis nanomedicine against pancreatic ductal adenocarcinoma (PDAC) is severely limited by cancer stem cells (CSCs), which reside in the hypoxic stroma and adopt glycolysis metabolism accordingly to resist cuproptosis-induced mitochondria damage. Here, we leverage hyperbaric oxygen (HBO) to regulate CSC metabolism by overcoming tumor hypoxia and to augment CSC elimination efficacy of polydopamine and hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanoparticles (CuET@PH NPs). Mechanistically, while HBO and CuET@PH NPs inhibit glycolysis and oxidative phosphorylation, respectively, the combination of HBO and CuET@PH NPs potently suppresses energy metabolism of CSCs, thereby achieving robust tumor inhibition of PDAC and elongating mice survival importantly. This study reveals novel insights into the effects of cuproptosis nanomedicine on PDAC CSC metabolism and suggests that the combination of HBO with cuproptosis nanomedicine holds significant clinical translation potential for PDAC patients.

Nanomedicine proofed to be efficient in cancer therapy but rapid clearance from blood circulation by reticuloendothelial system (RES) severely limits the antitumor efficacy. Here, the authors design a series of nanogels with distinctive stiffness and investigate how nanogel mechanical properties could be leveraged to overcome RES.

Abstract Tumor starvation induced by intratumor glucose depletion emerges as a promising strategy for anticancer therapy. However, its antitumor potencies are severely compromised by intrinsic tumor hypoxia, low delivery efficiencies, and undesired off‐target toxicity. Herein, a multifunctional cascade bioreactor (HCG), based on the self‐assembly of pH‐responsive hydroxyethyl starch prodrugs, copper ions, and glucose oxidase (GOD), is engineered, empowered by hyperbaric oxygen (HBO) for efficient cooperative therapy against aggressive breast cancers. Once internalized by tumor cells, HCG undergoes disassembly and releases cargoes in response to acidic tumor microenvironment. Subsequently, HBO activates GOD‐catalyzed oxidation of glucose to H2O2 and gluconic acid by ameliorating tumor hypoxia, fueling copper‐catalyzed •OH generation and pH‐responsive drug release. Meanwhile, HBO degrades dense tumor extracellular matrix, promoting tumor accumulation and penetration of HCG. Moreover, along with the consumption of glucose and the redox reaction of copper ions, the antioxidant capacity of tumor cells is markedly reduced, collectively boosting oxidative stress. As a result, the combination of HCG and HBO can not only remarkably suppress the growth of orthotopic breast tumors but also restrain pulmonary metastases by inhibiting cancer stem cells. Considering the clinical accessibility of HBO, this combined strategy holds significant translational potentials for GOD‐based therapies.

Summary: The formation of a compact and stable cathode electrolyte interphase (CEI) film is a promising way to improve the high voltage resistance of lithium-ion batteries (LIBs). However, challenges arise due to the corrosion of hydrogen fluoride (HF) and the dissolution of transition metal ions (TMs) in harsh conditions. To address this issue, researchers have constructed an anion-derived CEI film enriched with LiF and LiPO2F2 soluble product on the surface of LiNi0.5Mn1.5O4 (LNMO) cathode in highly concentrated electrolytes (HCEs). The strong binding of LiF and LiPO2F2 generated an inert LiPO2F2 soluble product interface, which inhibited HF corrosion and maintained the spinel structure of LNMO, contributing to a capacity retention of 92% after 200 cycles at 55°C in the resulting cell with a soluble LiPO2F2-containing CEI film. This new approach sheds light on improving the electrode/electrolyte interface for high-energy LIBs.

Layered P2-Na _0.67 Ni _0.15 Fe _0.2 Mn _0.65 O _2 (P2-NFM) cathode material has attracted great attention in sodium-ion batteries due to its high theoretical capacity, low cost, and environmental friendliness. However, P2-NFM exhibits irreversible phase transition and slip of transition metal layers in the high voltage range during charging process, leading to a gradually declined performance of the cathode material. It is therefore necessary to investigate the mechanism of phase transition of P2-NFM as well as the effect of phase transition on its performance. Herein, utilizing ex situ x-ray diffraction spectroscopy and x-ray photoelectron spectroscopy, the crystal structure and TM (transition-metal) bonding changes caused by phase transition are elucidated. It is found that P2-NFM is prone to undergo an irreversible P2-O2 phase transition at high voltage, causing changes in lattice parameters and rapid capacity decay. The irreversible phase transition is mainly due to he dynamic transformation of valence states of Fe and Ni in P2-NFM materials at high voltage. It is this process that results in irreversible fluctuations in the bond lengths between these elements and oxygen, consequently instigating interlayer slip within the material. Besides, the charge compensation mechanism of P2-NFM has been elucidated based on the study of its initial charging process. Results show that the charge compensation is mainly contributed by Ni and Fe in the high voltage range, while by a small amount of Mn in the low voltage range. It reveals the essential cause of the adverse phase transition of P2-NFM materials and points out the direction for improving the cycling stability of these layered oxide materials.

Cancer stem cells (CSCs) have been blamed as the main culprit of tumor initiation, progression, metastasis, chemoresistance, and recurrence. However, few anti-CSCs agents have achieved clinical success so far. Here we report a novel derivative of lonidamine (LND), namely HYL001, which selectively and potently inhibits CSCs by targeting mitochondria, with 380-fold and 340-fold lower IC50 values against breast cancer stem cells (BCSCs) and hepatocellular carcinoma stem cells (HCSCs), respectively, compared to LND. Mechanistically, we reveal that HYL001 downregulates glutaminase (GLS) expression to block glutamine metabolism, blunt tricarboxylic acid cycle, and amplify mitochondrial oxidative stress, leading to apoptotic cell death. Therefore, HYL001 displays significant antitumor activity in vivo, both as a single agent and combined with paclitaxel. Furthermore, HYL001 represses CSCs of fresh tumor tissues derived from liver cancer patients. This study provides critical implications for CSCs biology and development of potent anti-CSCs drugs.

Photodynamic therapy with reactive oxygen species production is a prospective treatment to combat cancer stem cells (CSCs). However, the innate drawbacks, including short lifetime and diffusion distance of reactive oxygen species and hypoxia within solid tumors, have become bottlenecks for clinical applications of photodynamic therapy. Here, we develop a mitochondria-targeting hemicyanine–oleic acid conjugate (CyOA), which can self-assemble into supramolecular nanoparticles (NPs) without any exogenous excipients. CyOA is also shown for targeting the mitochondrial complex II protein succinate dehydrogenase to inhibit oxidative phosphorylation and reverse tumor hypoxia, resulting in 50.4-fold higher phototoxicity against breast cancer stem cells (BCSCs) compared to SO3-CyOA NPs that cannot target to mitochondria. In 4T1 and BCSC tumor models, CyOA NPs achieve higher tumor inhibition and less lung metastasis nodules compared to the clinically used photosensitizer Hiporfin. This study develops a self-assembled small molecule that can serve as both oxidative phosphorylation inhibitor and photosensitizer for eradication of CSCs and treatment of solid tumors.

Li-rich manganese-based (LRM) cathode materials are known as one of the most promising cathode materials for new-generation lithium-ion batteries. At present, exploring the complex voltage decay mechanism of LRM is the main task to promote its commercialization. Herein, the structural evolution and transition metal valence state change of LRM during different reaction stages under different temperatures are discussed, and the mechanism of voltage decay is finally determined based on the electrochemical properties. The results show the evolution of irreversible thermodynamic structure is the fundamental cause leading to voltage decay of LRM cathode, and it worsens with increasing temperature. The early activation of inert Mn, multiple phase transitions, migration of transition metals to the surface, anisotropy of internal valence states caused by partial valence failure and severe interfacial reactions are all strong proofs of the above views. In summary, the reason for voltage decay is revealed by investigating the sensitivity of the LRM cathode materials to temperature. This work not only provides strong evidence for the mechanism of the voltage decay, but also points out the direction to modification design for achieving future commercialization of LRM cathode materials.

The development of high energy density LiNi0.5Mn1.5O4 (LNMO) cathode materials for lithium-ion batteries are challenged by capacity degradation, which becomes more aggravated particularly at elevated temperatures. Thus, the practical strategy with facile craft and the viability of large-scale preparation for industrialized applications should be developed urgently. In this work, a micron-sized LNMO single crystals is synthesized by a facile two-step method consisting of an alcohol gel solvent method and a segmented sintering reaction. Results show that the truncated polyhedron LNMO-900 sample, with the moderate D50 characteristic value of 4.429 μm and the highest tap density of 2.31 g cm−3, provides a stable structural and chemical stability even at elevated testing temperature due to its moderate specific surface area and the few Fd-3m phase. The LNMO/Li half-cells display more excellent capacity retention (87.3% at 1C and 25 °C after 500 cycles) and better thermal stability (76.65% at 1C and 55 °C after 200 cycles) than those of the single crystals of LNMO-850 and LNMO-950. Besides, the XPS, in-situ EIS and electrochemical tests results also prove that the LNMO-900 exhibits the lowest electrolyte decomposition degree, owing to a thin and effective solid-electrolyte interfacial film formed after cycles.

Abstract Engineering the solid electrolyte interphase (SEI) that forms on the electrode is crucial for achieving high performance in metal‐ion batteries. However, the mechanism of SEI formation resulting from electrolyte decomposition is not fully understood at the molecular scale. Herein, a new strategy of switching electrolyte to tune SEI properties is presented, by which a unique and thinner SEI can be pre‐formed on the graphite electrode first in an ether‐based electrolyte, and then the as‐designed graphite electrode can demonstrate extremely high‐rate capabilities in a carbonate‐based electrolyte, enabling the design of fast‐charging and wide‐temperature lithium‐ion batteries (e.g., graphite | LiNi0.6Co0.2Mn0.2O2 (NCM622)). A molecular interfacial model involving the conformations and electrochemical stabilities of the Li+‐solvent‐anion complex is presented to elucidate the differences in SEI formation between ether‐based and carbonate‐based electrolytes, then interpreting the reason for the obtained higher rate performances. This innovative concept combines the advantages of different electrolytes into one battery system. It is believed that the switching strategy and understanding of the SEI formation mechanism opens a new avenue to design SEI, which is universal for pursuing more versatile battery systems with greater stability.

The low electron/ion migration rate and the high deformability of conventional two-dimensional (2D) electrodes limit the growing demand for energy storage devices with high areal capacity and stable cycling performance. Designing three-dimensional (3D) electrodes is a promising strategy to improve this defect. Herein, we prepare metallic nickel aerogel via a facile hydrothermal reduction route, which was annealed to obtain a self-standing 3D porous NiO/Ni anode. The electrode material displays a networked porous structure and good electrical conductivity, which mitigates the volume effect during cycling and provides excellent electron transport pathways and conductive ion channels. The unique structure with many electrochemical active sites performs higher areal capacity. When used as the anode of lithium-ion batteries (LIBs), a high reversible areal capacity of 1.93 mAh cm−2 is delivered at a current density of 1 mA cm−2 with a capacity retention ratio of 98.4% after 100 cycles. Remarkably, a large reversible capacity of 1.30 mAh cm−2 is also achieved at a relatively high current density of 6 mA cm−2. The 3D porous NiO/Ni anode material provides a new strategy for enhancing the energy density and stable cycling for practical application in power-type LIBs.

Although pile-net composite foundation has been widely used in the construction of high-speed railway, load transfer characteristics of its structural system during the filling of roadbed are seldom studied, so field studies are conducted in the Gan-Long (Ganzhou-Longyan) high-speed railway DK86 + 998.0–DK87 + 191.2 test section, aiming to explore the bearing characteristics of a short pile-net composite foundation over low to medium compressible soil. The study encompasses a field measurement of Earth pressure and pore water pressure which lasted almost two years, and a systematic analysis of variation law of soil pressure between piles and their tops and that of pore pressure in reinforcement zone and retaining layer in medium and low compressibility soil area. The results suggest that the soil in the test section bears the characteristic of a low water content, low porosity ratio, and high liquid limit, with compression factor being approximately 0.25, and test values of the natural soil pressure and the lateral distribution are close to the theoretical values. Soil pressure at the top of the piles is higher than that between the piles by approximately 2.4 times because of the differences in pile-net rigidity. Besides, the soil pressure of the pile-net composite foundation follows the pattern of “jagged” in the transverse direction of the roadbed. The filling load of the composite foundation soil arch is 80 kPa and the composite foundation reaction coefficient is 6.4 kN/m3 when the filling is stable. The pile-soil stress ratio at the shoulder and the center of the line is 3.2 and 2.8, respectively. The change of the hole pressure at the pile end point is larger than that at the reinforcement area, and the side verification short pile can effectively transmit the additional stress of the upper part to the pile end soil layer.

The development of lithium-ion battery (LIB) has gone through nearly 40 year of research. The solid electrolyte interface film in LIBs is one of most vital research topics, its behavior affects the cycle life and safety of LIBs significantly. Progress in understanding the interfacial layer on the negative and positive electrodes in LIBs has been the focus of considerable research in the past few decades, but there remains a number of problem to be understood at the fundamental level, and there is still a great deal of controversy regarding the composition and formation mechanism of the interfacial film. In this article, we summarize recent research conducted on the interfacial film in LIBs, including the film formation mechanism, the composition, and stability of the interfacial film on the positive electrodes (in both diluted and high-concentration electrolytes). And the methodologies and advanced techniques implemented for the characterization of the interfacial film. Finally, we put forward some of the future development direction for the interfacial film and urgent problems that need to be solved.

Objective: Lipid droplet (LD) deposition in adipose tissue is a critical factor leading to metabolic dysfunction. Various herbal medicines in traditional Chinese medicine (TCM) are used to treat hyperlipidemia, type 2 diabetes, obesity, and other diseases. The objective of this study was to identify potential anti-adipogenic agents from TCM herbal compounds. Methods: One hundred and twenty compounds were evaluated in terms of their effect on adipocyte differentiation through image-based high content screening. Anti-adipogenic effects of identified hits were further confirmed at various concentrations. In addition, drug-induced liver injury assay was performed with HepG2 cells to test the hepatotoxicity of hit compounds. Results: Berbamine (BBM), a chemical isolated from barberry, and a derivative of BBM, berbamine dihydrochloride (BBMD), reduced LDs formation by more than 50%. Dose-dependent effects were observed and the IC50 values of the two hits, BBM and BBMD, were determined as 1.88 μM and 0.95 μM, respectively. Moreover, BBM induced mild HepG2 cell injury, while its dihydrochloride—BBMD did not exhibit hepatotoxicity within 40 μM. Conclusion: This study demonstrates that BBMD may be a potential therapeutic candidate for disorders associated with elevated LDs accumulation.

2,4-Di-tert-butylphenol or 2,4-bis(1,1-dimethylethyl)-phenol (2,4-DTBP) is a common toxic secondary metabolite produced by various groups of organisms. The biosources and bioactivities of 2,4-DTBP have been well investigated, but the phenol has not been systematically reviewed. This article provides a comprehensive review of 2,4-DTBP and its analogs with emphasis on natural sources and bioactivities. 2,4-DTBP has been found in at least 169 species of bacteria (16 species, 10 families), fungi (11 species, eight families), diatom (one species, one family), liverwort (one species, one family), pteridiphyta (two species, two families), gymnosperms (four species, one family), dicots (107 species, 58 families), monocots (22 species, eight families), and animals (five species, five families). 2,4-DTBP is often a major component of violate or essential oils and it exhibits potent toxicity against almost all testing organisms, including the producers; however, it is not clear why organisms produce autotoxic 2,4-DTBP and its analogs. The accumulating evidence indicates that the endocidal regulation seems to be the primary function of the phenols in the producing organisms.

The transient receptor potential ankyrin 1 (TRPA1) cation channel is one of the well-known targets for pain therapy. Herbal medicine is a rich source for new drugs and potentially useful therapeutic agents. To discover novel natural TRPA1 agonists, compounds isolated from Chinese herbs were screened using a cell-based calcium mobilization assay. Out of the 158 natural compounds derived from traditional Chinese herbal medicines, carnosol was identified as a novel agonist of TRPA1 with an EC50 value of 12.46 µM. And the agonistic effect of carnosol on TRPA1 could be blocked by A-967079, a selective TRPA1 antagonist. Furthermore, the specificity of carnosol was verified as it showed no significant effects on two other typical targets of TRP family member: TRPM8 and TRPV3. Carnosol exhibited anti-inflammatory and anti-nociceptive properties; the activation of TRPA1 might be responsible for the modulation of inflammatory nociceptive transmission. Collectively, our findings indicate that carnosol is a new anti-nociceptive agent targeting TRPA1 that can be used to explore further biological role in pain therapy.

The increasing demand for safe and effective treatments of chronic pain has promoted the investigation of novel analgesic drugs. Some herbals have been known to be able to relieve pain, while the chemical basis and target involved in this process remained to be clarified. The current study aimed to find anti-nociceptive candidates targeting transient receptor potential ankyrin 1 (TRPA1), a receptor that implicates in hyperalgesia and neurogenic inflammation. In the current study, 156 chemicals were tested for blocking HEK293/TRPA1 ion channel by calcium-influx assay. Docking study was conducted to predict the binding modes of hit compound with TRPA1 using Discovery Studio. Cytotoxicity in HEK293 was conducted by Cell Titer-Glo assay. Additionally, cardiotoxicity was assessed via xCELLigence RTCA system. We uncovered that cardamonin selectively blocked TRPA1 activation while did not interact with TRPV1 nor TRPV4 channel. A concentration-dependent inhibitory effect was observed with IC50 of 454 nM. Docking analysis of cardamonin demonstrated a compatible interaction with A-967079-binding site of TRPA1. Meanwhile, cardamonin did not significantly reduce HEK293 cell viability, nor did it impair cardiomyocyte constriction. Our data suggest that cardamonin is a selective TRPA1 antagonist, providing novel insight into the target of its anti-nociceptive activity.

Rattus tanezumi (Niethammer, 1975) is one of the commensal rodent species in South China. With the development of transportation and climate change, R. tanezumi has gradually migrated north and become the dominant rat species for the past few years. In this study, we assembled a complete mitochondrial genome of R. tanezumi, captured from North China. The mitogenome contains 16,307 nucleotide pairs, including 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes, as well as one non-coding control region. Based on whole mitogenome phylogenetical analysis showed that R. tanezumi captured from North China had a close phylogenetic relationship with that from Japan and South Korea. These findings are valuable for further studies on the evolution, genetic diversity, and taxonomy of Asian commensal rodent.