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Hexagonal boron nitride (h-BN) has excellent thermal conductivity and dielectric properties, which shows great potential for low-dimensional devices. However, mechanical properties of h-BN have not been comprehensively investigated through experiments. In this work, we conduct in situ direct tensile tests on freestanding single-crystal few-layer h-BN nanosheets with various layer numbers from 3 to 8, with an elaborate sample transfer and characterization protocol. Young's modulus of 573.8 ± 101.4 GPa and a tensile fracture strain up to 3.2% are revealed, which are comparable to its monolayer counterpart. Moreover, we find a tough-to-brittle transition in few-layer h-BN with the increase in layer number, which is attributed the interplay between the van der Waals interaction and in-plane covalent bonding. These findings could open up new possibilities in mechanical research of van der Waals materials and provide guidance for the design of h-BN-based devices and composites. [ABSTRACT FROM AUTHOR]

Four new sesquiterpenoids, talaroterpenes A–D (1–4), were isolated from the mangrove-derived fungus Talaromyces sp. SCSIO 41412. The structures of compounds 1–4 were elucidated through comprehensive NMR and MS spectroscopic analyses. The absolute configurations of 1–4 were assigned based on single-crystal X-ray diffraction and calculated electronic circular dichroism analysis. Talaroterpenes A–D (1–4) were evaluated with their regulatory activities on nuclear receptors in HepG2 cells. Under the concentrations of 200 μM, 1, 3 and 4 exhibited varying degrees of activation on ABCA1 and PPARα, while 4 showed the strongest activities. Furthermore, 4 induced significant alterations in the expression of downstream target genes CLOCK and BMAL1 of RORα, and the in silico molecular docking analysis supported the direct binding interactions of 4 with RORα protein. This study revealed that talaroterpene D (4) was a new potential non-toxic modulator of nuclear receptors. [ABSTRACT FROM AUTHOR]

Two new C23-steroids derivatives, cyclocitrinoic acid A (1) and cyclocitrinoic acid B (2), and a new isocoumarin metabolite, (3R,4S)-6,8-dihydroxy-3,4,5-trimethyl-7-carboxamidelisocoumarin (10), together with 12 known compounds (3–9, 11–15) were isolated from the mangrove-sediment fungus Penicillium sp. SCSIO 41429. The structures of the new compounds were comprehensively characterized by 1D and 2D NMR, HRESIMS and ECD calculation. All isolates were evaluated for pancreatic lipase (PL) inhibitory and antioxidant activities. The biological evaluation results revealed that compounds 2, 14 and 15 displayed weak or moderate inhibition against PL, with IC50 values of 32.77, 5.15 and 2.42 µM, respectively. In addition, compounds 7, 12 and 13 showed radical scavenging activities against DPPH, with IC50 values of 64.70, 48.13, and 75.54 µM, respectively. In addition, molecular docking results indicated that these compounds had potential for PL inhibitory and antioxidant activities, which provided screening candidates for antioxidants and a reduction in obesity. [ABSTRACT FROM AUTHOR]

Three new polyketides, including three ester derivatives (1, 3, and 5) and a new natural product, which was a benzoquinone derivative, embelin A (4), together with nine known ones (2 and 6–13), were isolated from the mangrove-derived fungus Penicillium sp. SCSIO 41411. Their structures were determined by detailed NMR and MS spectroscopic analyses. The X-ray single-crystal diffraction analysis of 4 was described for the first time. Compound 9 displayed obvious inhibition against PDE4 with an inhibitory ratio of 40.78% at 10 μM. Compound 12 showed DPPH radical scavenging activity, with an EC50 of 16.21 µg/mL, compared to the positive control (ascorbic acid, EC50, 11.22 µg/mL). Furthermore, compound 4 exhibited cytotoxicity against PC-3 and LNCaP with IC50 values of 18.69 and 31.62 µM, respectively. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor mutation variant III ( EGFR VIII) is a cancer-specific cell surface oncogenic marker and has been observed to be widely involved in the formation, progression and metastasis of lung cancer and some other tumors. Previously, a massive quantity of EGFR VIII -binding peptides were enriched via random phage display (RPD) targeted against the protein. In this study, we reported rational discovery of 12-mer peptides with high affinity to EGFR VIII and strong selectivity for EGFR VIII over wild-type EGFR ( EGFR WT). A combinatorial peptide library was designed to target EGFR VIII based on over ten thousands of known EGFR VIII binders enriched from RPD analysis, and a virtual high-throughput screening protocol was then systematically performed against the library to derive those potential candidates, which were further examined rigorously at structural and energetic levels to identify few promising hits. Anisotropy binding assays were carried out to substantiate the computational findings. Consequently, eight 12-mer peptides were designed as effective binders that can target the EGFR VIII extracellular subdomain 3 (SD3). In particular, two potent peptides (T1: FLHRYEIVTSYF and T3: FLQKYEWNTSYW) were found to have a high affinity to EGFR VIII and a good selectivity for EGFR VIII over EGFR WT . Structural analysis revealed that the peptide-binding site can be divided into hydrophobic, polar and mixed regions, which correspond to the nonpolar N -terminal section, polar/charged middle section and hybrid C-terminal section of the peptide. The peptide selectivity originated from the middle section, which can form a different hydrogen bond network between the two proteins upon the mutating perturbation, whereas the N- and C-terminal sections are primarily responsible for the peptide stability but not specificity. [ABSTRACT FROM AUTHOR]

One new quinazoline-containing diketopiperazine (1), along with 24 known compounds including nine alkaloids (2-9, and 25), thirteen lactones (10-22), aspterric acid (23), and catechol (24), were isolated from the marine sponge-derived Penicillium sp. SCSIO41043. Their planar structures were unequivocally elucidated by spectroscopic analysis. The absolute configuration of 1 was determined by a comparison of reported and experimental electronic circular dichroism (ECD) spectra. Compound 16 was found to notably inhibit the growth of five pathogenic bacteria and fungi with MIC values ranging from 0.5-16.0 μg/mL. Compounds 7, 17, 20, and 22 demonstrated moderate activity against Micrococcus luteus with MIC values ranging from 35.6 to 71.1 μg/mL. Moreover, 1-3 displayed different degrees of antioxidant activity with EC50 values of 0.98, 0.60, 0.46 mg/mL, respectively., (© 2024 Wiley‐VCH GmbH.)

Background: Elderly patients with esophageal cancer can benefit from concurrent chemoradiotherapy (CCRT). However, the optimal concurrent chemotherapy regimen remains undetermined. We aimed to compare the efficacy and safety of CCRT with paclitaxel-based or S-1 regimens in treating elderly patients with esophageal squamous cell carcinoma (ESCC)., Methods: From January 2016 to November 2022, a total of 349 patients aged 70 and above with ESCC were included. The patient population was divided into two treatment groups: patients receiving paclitaxel-based CCRT were allocated to the TP group, and those receiving S-1 regimen CCRT were allocated to the S-1 group. Propensity score matching (PSM) was used to balance potential biases. Survival outcomes, overall response rate, and treatment-related toxicities were assessed., Results: After PSM, there were 82 patients in each group. The median follow up of the surviving patients was 42.6 months (IQR 28.0-58.8 months). The 2-year overall survival (OS) rate (71.4% vs 65.4%; log-rank P = 0.010) and progression-free survival (PFS) rate (64.4% vs 58.0%; log-rank P = 0.048) were significantly higher in the TP group. Compared with the S-1 group, the TP group experienced a higher rate of grade 3 and above hematologic toxicities, such as leukopenia (47.6% vs 15.9%, P < 0.001) and neutropenia (35.4% vs 6.1%, P < 0.001). One patient in the TP group and two patients in the S-1 group had grade 5 toxic effects., Conclusions: Our findings suggest that paclitaxel-based CCRT was well tolerated in elderly patients with ESCC and provided significant survival benefits over S-1 regimen., 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., (Copyright © 2024. Published by Elsevier Inc.)

Excessive reactive oxygen species (ROS) and bacterial infection significantly disrupt the microenvironment of tissue regeneration. Magnetic nanoparticles in combination with magnetic fields are emerging strategies to regulate tissue regeneration. In this work, ZnFe 2 O 4 (ZFO) nanoparticles were prepared and subsequently decorated with polydopamine (PDA) and RGD peptide. The modified ZFO nanoparticles were loaded into polylactic-glycolic acid/polycaprolactone (PLGA/PCL) scaffolds as PP-ZFO/PDA-RGD magnetic scaffolds. Physicochemical, anti-ROS, antibacterial and osteogenic properties were evaluated in vitro. Under 30 mT static magnetic field, the PP-ZFO/PDA-RGD scaffold significantly enhanced the expression of ALP, RUNX2, BMP2 and mineralized nodules. It indicated that the magnetic system could promote the attachment, proliferation, differentiation and mineralization of MC3T3-E1 cells. The scaffold showed excellent ROS scavenging ability via the additive effect of ZFO, PDA and RGD. The remarkable antibacterial properties of Zn²⁺ and Fe³⁺ endowed the scaffolds with excellent antibacterial activity against E. coli and S. aureus. These results demonstrate that the PP-ZFO/PDA-RGD based magnetic system is a promising approach for bone regeneration under complex microenvironment., 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A dimeric citrinin derivative with a unique spiro[chroman-2,3'-isochroman] skeleton, xerucitrinic acid C (1), and a new citrinin derivative, cladosporin E (6), along with ten known polyketides (2-5 and 7-12), were isolated from the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41428. Their structures were elucidated through comprehensive spectral data analysis. The absolute configurations of 1 and 6 were determined by quantum chemical calculations. Compound 1 exhibited significant inhibitory effects on Staphylococcus aureus and Streptococcus suis, with the MIC of 25 μg/mL for both bacterial strains. Xerucitrinin C (3) exhibited significant radical scavenging activity against DPPH, with an IC50 value of 25.4 μM, and also demonstrated inhibitory activity against phosphodiesterase-4 (PDE4). Moreover, cladosporin C (7) notably inhibited prostate cancer cells PC-3 and 22Rv1, with IC50 values of 6.10 and 9.25 μM, respectively., (© 2024 Wiley‐VCH GmbH.)

Diabetic kidney disease (DKD) is one of the leading causes of end-stage renal disease worldwide and significantly increases the risk of premature death due to cardiovascular diseases. Elevated urinary albumin levels are an important clinical feature of DKD. Effective control of albuminuria not only delays glomerular filtration rate decline but also markedly reduces cardiovascular disease risk and all-cause mortality. New drugs for treating DKD proteinuria, including sodium-glucose cotransporter two inhibitors, mineralocorticoid receptor antagonists, and endothelin receptor antagonists, have shown significant efficacy. Auxiliary treatment with proprietary Chinese medicine has also yielded promising results; however, it also faces a broader scope for development. The mechanisms by which these drugs treat albuminuria in patients with DKD should be described more thoroughly. The positive effects of combination therapy with two or more drugs in reducing albuminuria and protecting the kidneys warrant further investigation. Therefore, this review explores the pathophysiological mechanism of albuminuria in patients with DKD, the value of clinical diagnosis and prognosis, new progress and mechanisms of treatment, and multidrug therapy in patients who have type 2 diabetic kidney disease, providing a new perspective on the clinical diagnosis and treatment of DKD., 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., (Copyright © 2024 Zhang, Wang, Li, Li, Zhou, Chen and Dong.)

Proton tunneling is believed to be nonlocal in ice, but its range has been shown to be limited to only a few molecules. Here, we measured the thermal conductivity of ice under pressure up to 50 GPa and found it increases with pressure until 20 GPa but decreases at higher pressures. We attribute this nonmonotonic thermal conductivity to the collective tunneling of protons at high pressures, supported by large-scale quantum molecular dynamics simulations. The collective tunneling loops span several picoseconds in time and are as large as nanometers in space, which match the phonon periods and wavelengths, leading to strong phonon scattering at high pressures. Our results show direct evidence of global quantum motion existing in high-pressure ice and provide a new perspective to understanding the coupling between phonon propagation and atomic tunneling.