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Metal-organic frameworks (MOFs) have great prospects as adsorbents for industrial gas purification, but often suffer from issues of water stability and competitive water adsorption. Herein, we present a hydrolytically stable MOF that could selectively capture and recover trace SO 2 from flue gas, and exhibits remarkable recyclability in the breakthrough experiments under wet flue-gas conditions, due to its excellent resistance to the corrosion of SO 2 and the water-derived capillary forces. More strikingly, its SO 2 capture efficiency is barely influenced by the increasing humidity, even if the pore filling with water is reached. Mechanistic studies demonstrate that the delicate pore structure with diverse pore dimensions and chemistry leads to different adsorption kinetics and thermodynamics as well as segregated adsorption domains of SO 2 and H 2 O. Significantly, this non-competitive adsorption mechanism enables simultaneous desulfurization and dehydration by a single adsorbent, opening an avenue toward cost-effective and simplified processing flowcharts for flue gas purification., (© 2024 Wiley-VCH GmbH.)

Background: Cyclophosphamide (CTX) is the first-line medication for the treatment of breast cancer, although it potentially leads to severe ovarian dysfunction and even premature ovarian failure (POF). However, the mechanism of CTX-induced POF remains unclear. Mesenchymal stem cell-based therapy has been wildly used for treating numerous diseases. Therefore, our study aims to elucidate the underlying mechanism of CTX-induced POF and to explore the therapeutic effect of human urine stem cells (hUSCs) in POF., Methods: CTX-induced POF or ovarian granulosa cell (GCs) apoptosis were treated with hUSCs and their exosomes in vitro and in vivo. Morphological, histological, and functional alternations were examined using multiple approaches. The effector molecules of hUSC-derived exosomes (hUSC-Exo) were determined by differential expression analysis in the ovaries. The target genes of miRNA were accessed by transcriptome sequencing in GCs, and the underlying mechanisms were further elucidated., Results: hUSCs remarkably inhibited CTX-induced apoptosis and promoted the proliferation of GCs, respectively. In addition, we observed that miR-27b-3p was highly expressed in hUSC-Exo and markedly suppressed CTX-induced GC apoptosis by specifically inhibiting the expression of SLC1A4, a serine transporter, in ovarian GCs, which, in turn, elevated the concentration of the intracellular serine by inhibiting the outflux of cellular serine. More importantly, the knockdown of SLC1A4 or simple supplementation of serine suppressed CTX-induced apoptosis of GCs. Finally, we demonstrated that CTX-induced apoptosis of ovarian GCs was essential for POF by reducing the intracellular serine concentration via elevating the expression of SLC1A4, whereas hUSCs protected against CTX-induced POF via miR-27b-3p/SLC1A4/serine axis-mediated activation of the PI3K/AKT/mTOR signaling pathway., Conclusions: Our study suggests that hUSC-based cell therapy or simple supplementation of serine may provide an efficient therapeutic approach for the prevention and treatment of CTX-induced POF clinically., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted following the Declaration of Helsinki (as revised in 2013), and written consent for tissue donation was obtained from each patient. The protocol was approved by the Institutional Review Board of the First Affiliated Hospital of Nanchang University (approval no. 2023CDYFYYLK08-015; approval date 11 August 2023). The protocols were approved by the Animal Research Ethics Board of Nanchang University (approval no. 20X045; approval date 2 July 2020), following the Guidelines for the Care and Use of Animals. The study involving animals was conducted following the Basel Declaration. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The unique 4f subshell electronic structure of rare earth elements endows them with exceptional properties in electrical, magnetic, and optical domains. These properties include prolonged fluorescence lifetimes, large Stokes shifts, distinctive spectral bands, and strong resistance to photobleaching, making them ideal for the synthesis of molecular probes. Each imaging technique possesses unique advantages and specific applicabilities but also inherent limitations due to its operational principles. Dual-modality molecular probes effectively address these limitations, particularly in applications involving high-resolution Magnetic Resonance Imaging (MRI) such as MRI/OI, MRI/PET, MRI/CT, and MRI/US. This review summarizes the applications, advantages, challenges, and current research status of rare earth elements in these four dual imaging modalities, providing a theoretical basis for the future development and application of rare earth elements in the field of dual-modality molecular probes., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Mitotic anaphase onset is a key cellular process tightly regulated by multiple kinases. The involvement of mitogen-activated protein kinases (MAPKs) in this process has been established in Xenopus egg extracts. However, the detailed regulatory cascade remains elusive, and it is also unknown whether the MAPK-dependent mitotic regulation is evolutionarily conserved in the single-cell eukaryotic organisms such as fission yeast ( Schizosaccharomyces pombe ). Here, we show that two MAPKs in S. pombe indeed act in concert to restrain anaphase-promoting complex/cyclosome (APC/C) activity upon activation of the spindle assembly checkpoint (SAC). One MAPK, Pmk1, binds to and phosphorylates Slp1 Cdc20 , the co-activator of APC/C. Phosphorylation of Slp1 Cdc20 by Pmk1, but not by Cdk1, promotes its subsequent ubiquitylation and degradation. Intriguingly, Pmk1-mediated phosphorylation event is also required to sustain SAC under environmental stress. Thus, our study establishes a new underlying molecular mechanism of negative regulation of APC/C by MAPK upon stress stimuli, and provides a previously unappreciated framework for regulation of anaphase entry in eukaryotic cells., Competing Interests: LS, XC, CS, WS, LL, SB, XW, JC, CJ, SW, ZL, RW, YW, QJ No competing interests declared, (© 2024, Sun, Chen, Song et al.)

α-Cobalt(II) (Co II ) hydroxide (compound 1 ) incorporating cyanuric acid layers was synthesized via the solvothermal method. 1 exhibited two distinct characteristics, which were different from reported α-Co II hydroxides. (i) The presence of abundant consecutive hydrogen bonds between the adjacent hydroxide layers enhanced the driving force of crystallization along the direction of the c axis. Thus, 1 revealed high crystallinity without the disorder phenomenon. (ii) 1 showed low symmetry. The configuration of Co Td sites did not follow the regular triangular net. The low symmetry favored the magnetic anisotropy. Thus, 1 revealed ferrimagnetic behavior with a high Néel temperature ( T N = 56.8 K) and coercivity ( H c = 36 kOe at 2 K). The ferrimagnetic behavior of 1 was validated via the Hubbard U correction density functional theory.

Aims: Despite islet transplantation has proved a great potential to become the standard therapy for type 1 diabetes mellitus (T1DM), this approach remains limited by ischemia, hypoxia, and poor revascularization in early post-transplant period as well as inflammation and life-long host immune rejection. Here, we investigate the potential and mechanism of human amniotic mesenchymal stem cells (hAMSCs)-islet organoid to improve the efficiency of islet engraftment in immunocompetent T1DM mice., Main Methods: We generated the hAMSC-islet organoid structure through culturing the mixture of hAMSCs and islets on 3-dimensional-agarose microwells. Flow cytometry, whole-body fluorescent imaging, immunofluorescence, Calcein-AM/PI staining, ELISA, and qPCR were used to assess the potential and mechanism of shielding hAMSCs to improve the efficiency of islet transplantation., Key Findings: Transplant of hAMSC-islet organoids results in remarkably better glycemic control, an enhanced glucose tolerance, and a higher β cell mass in vivo compared with control islets. Our results show that hAMSCs shielding provides an immune privileged microenvironment for islets and promotes graft revascularization in vivo. In addition, hAMSC-islet organoids show higher viability and reduced dysfunction after exposure to hypoxia and inflammatory cytokines in vitro. Finally, our results show that shielding with hAMSCs leads to the activation of PKA-CREB-IRS2-PI3K and PKA-PDX1 signaling pathways, up-regulation of SIL1 mRNA levels, and down-regulation of MT1 mRNA levels in β cells, which ultimately promotes the synthesis, folding and secretion of insulin, respectively., Significance: hAMSC-islet organoids can evidently increase the efficiency of islet engraftment and might develop into a promising alternative for the clinical treatment of T1DM., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Fe(II) regeneration is decisive for highly efficient H 2 O 2 -based Fenton-like processes, but the role of cobalt-containing reactive sites in promoting Fe(II) regeneration was overlooked. Herein, a single atom Co-N-C catalyst was employed in Fe(II)/H 2 O 2 system to promote the degradation of diverse organic contaminants. The EPR and quenching experiments indicated Co-N-C significantly enhanced the generation of superoxide species, and accelerated hydroxyl radical generation for pollutant degradation. The electrochemical and surface composition analyses demonstrated the enhanced H 2 O 2 activation and Fe(III)/Fe(II) recycling on the catalyst. Furthermore, in-situ Raman characterization with shell-isolated gold nanoparticles was employed to visualize the interfacial reactive intermediates and their time-resolved interaction. The accumulation of interfacial CoOOH* was confirmed when Co-N-C activated H 2 O 2 alone, but it rapidly transformed into FeOOH* upon Fe(II) addition. Besides, the temporal variation of OOH* intermediates and the relative intensity of Co(III)-O and Co(IV)=O peaks depicted the dynamic interaction of reactive intermediates along the H 2 O 2 consumption. With this basis, we proposed a mechanism of interfacial OOH* mediated Fe(II) regeneration, which overcame the kinetical limitation of Fe(II)/H 2 O 2 system. Therefore, this study provided a primary effort to elucidate the overlooked role of interfacial CoOOH* in the Fenton-like processes, which may inspire the design of more efficient catalysts., 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.)

Genome-wide circulating cell-free DNA (ccfDNA) fragmentation for cancer detection has been rarely evaluated using blood samples collected before cancer diagnosis. To evaluate ccfDNA fragmentation for detecting early hepatocellular carcinoma (HCC), we first modeled and tested using hospitalized HCC patients and then evaluated in a population-based study. A total of 427 samples were analyzed, including 270 samples collected prior to HCC diagnosis from a population-based study. Our model distinguished hospital HCC patients from controls excellently (area under curve 0.999). A high ccfDNA fragmentation score was highly associated with an advanced tumor stage and a shorter survival. In evaluation, the model showed increasing sensitivities in detecting HCC using 'pre-samples' collected ≥4 years (8.3%), 3-4 years (20.0%), 2-3 years (31.0%), 1-2 years (35.0%), and 0-1 year (36.4%) before diagnosis. These findings suggested ccfDNA fragmentation is sensitive in clinical HCC detection and might be helpful in screening early HCC., Competing Interests: Z.Z. receives patent royalty from ArcherDX; is a scientific advisor for and holds equity in GenEditBio; these interests are reviewed and regulated by institutional Outside Practice and Outside Work policies annually. Z.Z. and S.L. have filed patent based on the WGS method. The other authors declare no competing interests., (© 2024 The Author(s).)

Eukaryotic cells are constantly exposed to various environmental stimuli. It remains largely unexplored how environmental cues bring about epigenetic fluctuations and affect heterochromatin stability. In the fission yeast Schizosaccharomyces pombe , heterochromatic silencing is quite stable at pericentromeres but unstable at the mating-type ( mat ) locus under chronic heat stress, although both loci are within the major constitutive heterochromatin regions. Here, we found that the compromised gene silencing at the mat locus at elevated temperature is linked to the phosphorylation status of Atf1, a member of the ATF/CREB superfamily. Constitutive activation of mitogen-activated protein kinase (MAPK) signaling disrupts epigenetic maintenance of heterochromatin at the mat locus even under normal temperature. Mechanistically, phosphorylation of Atf1 impairs its interaction with heterochromatin protein Swi6 HP1 , resulting in lower site-specific Swi6 HP1 enrichment. Expression of non-phosphorylatable Atf1, tethering Swi6 HP1 to the mat3M -flanking site or absence of the anti-silencing factor Epe1 can largely or partially rescue heat stress-induced defective heterochromatic maintenance at the mat locus., Competing Interests: LS, LL, CS, YW, QJ No competing interests declared, (© 2024, Sun, Liu, Song et al.)

The efficiency and cognitive limitations of manual sample labeling result in a large number of unlabeled training samples in practical applications. Making full use of both labeled and unlabeled samples is the key to solving the semi-supervised problem. However, as a supervised algorithm, the stacked autoencoder (SAE) only considers labeled samples and is difficult to apply to semi-supervised problems. Thus, by introducing the pseudo-labeling method into the SAE, a novel pseudo label-based semi-supervised stacked autoencoder (PL-SSAE) is proposed to address the semi-supervised classification tasks. The PL-SSAE first utilizes the unsupervised pre-training on all samples by the autoencoder (AE) to initialize the network parameters. Then, by the iterative fine-tuning of the network parameters based on the labeled samples, the unlabeled samples are identified, and their pseudo labels are generated. Finally, the pseudo-labeled samples are used to construct the regularization term and fine-tune the network parameters to complete the training of the PL-SSAE. Different from the traditional SAE, the PL-SSAE requires all samples in pre-training and the unlabeled samples with pseudo labels in fine-tuning to fully exploit the feature and category information of the unlabeled samples. Empirical evaluations on various benchmark datasets show that the semi-supervised performance of the PL-SSAE is more competitive than that of the SAE, sparse stacked autoencoder (SSAE), semi-supervised stacked autoencoder (Semi-SAE) and semi-supervised stacked autoencoder (Semi-SSAE).

Lanthanide metal-organic frameworks (Ln-MOFs) are promising for luminescence detection of volatile organic compound (VOC) vapors, but usually suffer from the silent or quenched Ln 3+ emission. Herein, we report a new dual-emissive Eu-MOF composed of the coordinatively unsaturated Eu 9 clusters that afford abundant open metal sites to form a confined "binding pocket" to facilitate the preconcentration and recognition of VOCs. Single-crystal structural analyses reveal that specific analytes can replace the OH oscillators in the first coordination sphere of Eu 3+ and form a unique hydrogen-bonding second-sphere adduct tying adjacent Eu 9 clusters together to minimize their nonradiative vibrational decay. With the promoted Eu 3+ luminescence, the MOF realizes real-time in situ visual sensing of THF vapor (<1 s) and shows a quantitative ratiometric response to the vapor pressure with a limit of detection down to 17.33 Pa. Also, it represents a top-performing ratiometric luminescent thermometer., (© 2022 Wiley-VCH GmbH.)

Pteris cretica L. var. nervosa is one of the most well-known Chinese medicines. Although it is widely used to treat jaundice hepatitis, the main ingredient for its treatment was not thoroughly explored until recently. Essentially, the purpose of this study is to find the monomer compound in Pteris cretica L. var. nervosa, which is most likely to be effective in treating liver injury. Through the model of LPS/D-gal-induced liver injury in mice, the best therapeutic site of the total extract was explored, the chemical components of the parts with the best therapeutic effect were separated, a total of 10 flavonoids were isolated, and the RAW264.7 cells induced by LPS were used as the experimental model to explore the preliminary anti-inflammatory activity of NO production in vitro. Finally, the anti-inflammatory activity and the highest content in this plant Luteolin-7-O-rutinoside (LUT) were selected, as the object of study in vivo. It was found that LUT could not only reduce alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, but also significantly reduce the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and inhibit PI3K/AKT/AMPK/NF-κB pathway. In addition, LUT can increase levels of SOD and GSH to reduce oxidative stress. It has an obvious therapeutic effect on acute liver injury induced by LPS/D-gal in mice. Therefore, infer LUT is a functional substance in Pteris cretica L. var. nervosa., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Microtubules play a crucial role during the establishment and maintenance of cell polarity. In fission yeast cells, the microtubule plus-end tracking proteins (+TIPs) (including the CLIP-170 homologue Tip1) regulate microtubule dynamics and also transport polarity factors to the cell cortex. Here, we show that the E3 ubiquitin ligase Dma1 plays an unexpected role in controlling polarized growth through ubiquitinating Tip1. Dma1 colocalizes with Tip1 to cortical sites at cell ends, and is required for ubiquitination of Tip1. Although the absence of dma1 + does not cause apparent polar growth defects in vegetatively growing cells, Dma1-mediated Tip1 ubiquitination is required to restrain polar growth upon DNA replication stress. This mechanism is distinct from the previously recognized calcineurin-dependent inhibition of polarized growth. In this work, we establish a link between Dma1-mediated Tip1 ubiquitination and DNA replication or DNA damage checkpoint-dependent inhibition of polarized growth in fission yeast., (© 2022. The Author(s).)

The activated spindle assembly checkpoint (SAC) potently inhibits the anaphase-promoting complex/cyclosome (APC/C) to ensure accurate chromosome segregation at anaphase. Early studies have recognized that the SAC should be silenced within minutes to enable rapid APC/C activation and synchronous segregation of chromosomes once all kinetochores are properly attached, but the underlying silencers are still being elucidated. Here, we report that the timely silencing of SAC in fission yeast requires dnt1+, which causes severe thiabendazole (TBZ) sensitivity and increased rate of lagging chromosomes when deleted. The absence of Dnt1 results in prolonged inhibitory binding of mitotic checkpoint complex (MCC) to APC/C and attenuated protein levels of Slp1Cdc20, consequently slows the degradation of cyclin B and securin, and eventually delays anaphase entry in cells released from SAC activation. Interestingly, Dnt1 physically associates with APC/C upon SAC activation. We propose that this association may fend off excessive and prolonged MCC binding to APC/C and help to maintain Slp1Cdc20 stability. This may allow a subset of APC/C to retain activity, which ensures rapid anaphase onset and mitotic exit once SAC is inactivated. Therefore, our study uncovered a new player in dictating the timing and efficacy of APC/C activation, which is actively required for maintaining cell viability upon recovery from the inhibition of APC/C by spindle checkpoint., Competing Interests: The authors have declared that no competing interests exist.

As a surveillance mechanism, the activated spindle assembly checkpoint (SAC) potently inhibits the E3 ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) to ensure accurate chromosome segregation. Although the protein phosphatase 2A (PP2A) has been proposed to be both, directly and indirectly, involved in spindle assembly checkpoint inactivation in mammalian cells, whether it is similarly operating in the fission yeast Schizosaccharomycer pombe has never been demonstrated. Here, we investigated whether fission yeast PP2A is involved in SAC silencing by following the rate of cyclin B (Cdc13) destruction at SPBs during the recovery phase in nda3-KM311 cells released from the inhibition of APC/C by the activated spindle checkpoint. The timing of the SAC inactivation is only slightly delayed when two B56 regulatory subunits (Par1 and Par2) of fission yeast PP2A are absent. Overproduction of individual PP2A subunits either globally in the nda3-KM311 arrest-and-release system or locally in the synthetic spindle checkpoint activation system only slightly suppresses the SAC silencing defects in PP1 deletion (dis2Δ) cells. Our study thus demonstrates that the fission yeast PP2A is not a key regulator actively involved in SAC inactivation., (© 2022 Federation of American Societies for Experimental Biology.)

Efficient magnetic solid phase extraction using crystalline porous polymers can find important applications in food safety. Herein, the core-shell Fe 3 O 4 @COFs nanospheres were synthesized by one-pot method and characterized in detail. The porous COF shell with large surface area had fast and selective adsorption for propylparaben via π-π, hydrogen bonding and hydrophobic interactions. The extraction and desorption parameters were evaluated in detail. Under the optimized conditions, the extraction equilibrium was reached only in 5 min, the maximum adsorption capacity for propylparaben was 500 mg g -1 and the proposed Fe 3 O 4 @DhaTab-based-MSPE-HPLC-UV method afforded good linearity (4-20000 μg mL -1 ) with R 2 (0.997), low limits of detection (0.55 μg L -1 ) and limits of quantification (1.5 μg L -1 ). Furthermore, the developed method was applied to determine propylparaben in soft drinks with the recoveries (97.0-98.3%) and relative standard deviations (0.61 to 3.75%). These results revealed the potential of Fe 3 O 4 @DhaTab as efficient adsorbents for parabens in food samples., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Covalent organic framework (COF)-decorated magnetic nanoparticles (Fe 3 O 4 @DhaTab) with core-shell structure have been synthesized by one-pot method. The prepared Fe 3 O 4 @DhaTab was well characterized, and parameters of magnetic solid-phase extraction (MSPE) for parabens were also investigated in detail. Under optimized conditions, the adsorbent dosage was only 3 mg and extraction time was 10 min. The developed Fe 3 O 4 @DhaTab-based MSPE-HPLC analysis method offered good linearity (0.01-20 μg mL -1 ) with R 2 (0.999) and low limits of detection (3.3-6.5 μg L -1 ) using UV detector at 254 nm. The proposed method was applied to determine four parabens in environmental water samples with recoveries in the range 64.0-105% and relative standard deviations of 0.16-7.8%. The adsorption mechanism was explored and indicated that porous DhaTab shell provided π-π, hydrophobic, and hydrogen bonding interactions in the MSPE process. The results revealed the potential of magnetic-functionalized COFs in determination of environmental contaminants., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Singlet oxygen ( 1 O 2 ) is a promising reactive species for the selective degradation of organic pollutants. However, it is difficult to generate 1 O 2 from H 2 O 2 activation with high efficiency and selectivity. In this work, a graphene-supported highly dispersed cobalt catalyst with abundant Co-N x active sites (Co-N-graphene) was synthesized for activating H 2 O 2 . The Co-N-graphene catalyzed H 2 O 2 reaction system selectively catalyzed 1 O 2 production associated with the superoxide radical (O 2 ˙ - ) as the critical intermediate, as proven by scavenger experiments, electron spin resonance (ESR) spin trapping and a kinetic solvent isotope effect study. This resulted in excellent degradation efficiency towards the model organic pollutant methylene blue (MB), with an outstanding pseudo-first-order kinetic rate constant of 0.432 min -1 (g L catalyst -1 ) -1 under optimal reaction conditions ( C H 2 O 2 = 400 mM, initial pH = 9). Furthermore, this Co-N-graphene catalyst enabled strong synergy with HCO 3 - in accelerating MB degradation, whereas the scavenger experiment implied that the synergy herein differed significantly from the current Co 2+ -HCO 3 - reaction system, in which contribution of O 2 ˙ - was only validated with a Co-N-graphene catalyst. Therefore, this work developed a novel catalyst for boosting 1 O 2 production from H 2 O 2 activation and will extend the inventory of catalysts for advanced oxidation processes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Liver fibrosis is an outcome of restoring process in chronic liver injury. Human amniotic mesenchymal stem cells (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential which makes them suitable for treating liver fibrosis. This study aimed to explore the effect and mechanism of hAMSCs on liver fibrosis., Methods: hAMSCs were transplanted into carbon tetrachloride (CCl 4 )-induced liver fibrosis mice via tail vein, and the effects of hAMSCs on hepatic fibrosis were assessed. The effects of hAMSCs and hAMSCs conditional medium (CM) on the activation of hepatic stellate cells (HSCs) were investigated in vivo and in vitro. Antibody array assay was used to identify the cytokines secreted by hAMSCs that may inhibit the activation of HSCs. Finally, the underlying mechanisms were explored by assessing IGF-1R/PI3K/AKT and GSK3β/β-catenin signaling pathways in the activated HSCs (LX-2) with hAMSCs and hAMSCs transfected with corresponding siRNAs., Results: Our results showed that hAMSCs possessed the characterizations of mesenchymal stem cells. hAMSCs significantly reduced liver fibrosis and improved liver function in mice by inhibiting HSCs activation in vivo. Both hAMSCs and hAMSC-CM remarkably inhibited the collagen deposition and activation of LX-2 cells in vitro. Antibody array assay showed that insulin-like growth factor binding protein-3 (IGFBP-3), Dickkopf-3 (DKK-3), and Dickkopf-1 (DKK-1) were highly expressed in the co-culture group and hAMSC-CM group compared with LX-2 group. Western blot assay demonstrated that IGFBP-3, DKK-3, and DKK-1 derived from hAMSCs inhibit LX-2 cell activation through blocking canonical Wnt signaling pathway., Conclusions: Our results demonstrated that IGFBP-3, Dkk3, and DKK-1 secreted by hAMSCs attenuated liver fibrosis in mice through inhibiting HSCs activation via depression of Wnt/β-catenin signaling pathway, suggesting that hAMSCs or hAMSC-CM provides an alternative therapeutic approach for the treatment of liver fibrosis., (© 2022. The Author(s).)

Developing universal stimuli-responsive materials capable of emitting a broad spectrum of colors is highly desirable. Herein, we deliberately grafted a conformation-adaptable organic chromophore into the established coordination space of a flexible metal-organic framework (MOF). In terms of the coupled structural transformations and the space confinement, the chromophore in the MOF matrix underwent well-regulated conformational changes under physical and chemical stimuli, simultaneously displaying thermo-, piezo-, and solvato-fluoro-chromism with color tunability over the visible range. Owing to the resilient nature and the reduced dimensionality of the selected coordination space, all three color modulations behaved in a sensitive and self-reversible manner, each following a linear correlation of the emission maximum with stimulus. Single-crystal X-ray diffraction of the variable-temperature structures and solvent-inclusion crystals elucidated the intricate color varying mechanisms., (© 2022 Wiley-VCH GmbH.)

Penicillium oxalicum has been used as a biocontrol fungus in agriculture for many years, but the antimicrobial substances are still uncertain. Herein, we isolated a linear peptide named Sanxiapeptin in the culture broth of Penicillium oxalicum SG-4 collecting from the Three Gorges riparian zone. Sanxiapeptin exhibited potent inhibitory effect on citrus green mold Penicillium digitatum, the main fungi responsible for postharvest decay. Sanxiapeptin was elucidated as composing of five amino acids, which were β-amino-α-methoxybutyric acid (Amoba), N-Me-l-Thr, d-Thr, N-Me-l-Val and l-Ser. By analyzing three chemically synthesized oligopeptides with similar structures, we found that the first amino acid of Amoba was crucial to the antifungal activity, as was the methylation of peptide bond. Sanxiapeptin may act as an antimicrobial agent by affecting the function of cell membranes or walls. The antimicrobial spectrum, safety and stability analysis supported that Sanxiapeptin was a promising antifungal agent for citrus preservation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A molecular cytogenetic investigation was conducted on plants of the allohexaploid species Elymus nutans with varying fertility on the Qinghai-Tibet Plateau. Molecular karyotyping revealed that chromosome variants were distributed unevenly among genomes and among different homologue chromosomes in each genome. The plants with varying fertility exhibited significantly higher numbers of chromosome variants than did the normal fertility samples, although both kinds of plants showed the same pattern of high-to-low polymorphism from the Y to St and H genomes. Heterozygosis and karyotype heterozygosity in the plants with varying fertility were 3- and 13-fold higher than those in normal samples, respectively. Significant negative correlations were found not only between seed setting rates and total genome heterozygosity but also between seed setting rates and heterozygosity of each genome in the plants of varying fertility. Chromosome pairing analysis was performed using genomic in situ hybridization in selected plants of different fertility levels. The pairing of chromosomes at meiotic metaphase I was mostly bivalent, although univalent, trivalent, quadrivalent, and other polyvalents also occurred; in addition, chromosome configuration forms and frequencies varied among the studied samples. ANOVA results showed that the average number of ring bivalents in the Y genome was significantly higher than those in the St and H genomes. Significant positive correlations between pollen grain fertility and ring bivalent number were found in the St and H genomes but not in the Y genome. Furthermore, chromosome configuration parameters (total bivalents, numbers of ring and rod bivalents) were found to be significantly correlated with heterozygosity and seed setting rates in the St and H genomes, respectively, but not in the Y genome. It was inferred that the seed setting rate and pollen grain fertility in E. nutans are strongly influenced by the heterozygosity of each genome, but the Y genome differs from the St and H genomes due to chromosome pair alterations. The St and H genomes may contain more chromosome structural variations than the Y genome in E. nutans ., 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., (© 2021 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Phenotypic switching is the main cause of the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). We previously showed that Daxx exerted negative regulatory effect on AngII-induced VSMC proliferation and migration. However, the function of Daxx in VSMC phenotype switching remained unknown. Nicotinate-curcumin (NC) is an esterification derivative of niacin and curcumin that can prevent the formation of atherosclerosis. We found that NC significantly decreased AngII-induced VSMC phenotype switching. Furthermore, NC significantly inhibited AngII-induced cell proliferation and migration. Moreover, NC upregulated Daxx expression and regulated the PTEN/Akt signaling pathway. We concluded that NC inhibited AngII-induced VSMC phenotype switching by regulating the PTEN/Akt pathway, and through a mechanism that might be associated with the upregulation of Daxx expression.

Using genetic mutations to study protein functions in vivo is a central paradigm of modern biology. Single-domain camelid antibodies generated against GFP have been engineered as nanobodies or GFP-binding proteins (GBPs) that can bind GFP as well as some GFP variants with high affinity and selectivity. In this study, we have used GBP-mCherry fusion protein as a tool to perturb the natural functions of a few kinetochore proteins in the fission yeast Schizosaccharomyces pombe. We found that cells simultaneously expressing GBP-mCherry and the GFP-tagged inner kinetochore protein Cnp1 are sensitive to high temperature and microtubule drug thiabendazole (TBZ). In addition, kinetochore-targeted GBP-mCherry by a few major kinetochore proteins with GFP tags causes defects in faithful chromosome segregation. Thus, this setting compromises the functions of kinetochores and renders cells to behave like conditional mutants. Our study highlights the potential of using GBP as a general tool to perturb the function of some GFP-tagged proteins in vivo with the objective of understanding their functional relevance to certain physiological processes, not only in yeasts, but also potentially in other model systems., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

This study aimed to investigate the therapeutic potential of human umbilical cord mesenchymal stem cells derived exosomes (hUCMSC-Exo) in acute liver failure (ALF) in mice as well as its underlying mechanism. We found that a single tail vein administration of hucMSC-Exo effectively enhanced the survival rate, inhibited apoptosis in hepatocytes, and improved liver function in APAP-induced mouse model of ALF. Furthermore, the deletion of glutathione (GSH) and superoxide dismutase (SOD), generation of malondialdehyde (MDA), and the over production of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP were also inhibited by hucMSC-Exo, indicating that hucMSC-Exo inhibited APAP-induced apoptosis of hepatocytes by reducing oxidative stress. Moreover, hucMSC-Exo significantly down-regulated the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in APAP-treated livers. Western blot showed that hucMSC-Exo significantly promoted the activation of ERK1/2 and IGF-1R/PI3K/AKT signaling pathways in APAP-injured LO2 cells, resulting in the inhibition of apoptosis of LO2 cells. Importantly, PI3K inhibitor LY294002 and ERK1/2 inhibitor PD98059 could reverse the function of hucMSC-Exo on APAP-injured LO2 cells in some extent. Our results suggest that hucMSC-Exo offer antioxidant hepatoprotection against APAP in vitro and in vivo by inhibitiing oxidative stress-induced apoptosis via upregulation of ERK1/2 and PI3K/AKT signaling pathways., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Inflammation-induced activation and dysfunction of endothelial cells play an important role in the pathology of multiple vascular diseases. Nicaraven, a potent hydroxyl radical scavenger, has recently been found to have anti-inflammatory roles; however, the mechanism of its action is not fully understood. Here we investigated the effects of Nicaraven on tumor necrosis factor α (TNFα) - induced inflammatory response in human umbilical vein endothelial cells and we explore the underlying mechanisms related to the nuclear factor-κB (NF-κB) signaling pathway. Our results showed that Nicaraven significantly reduced the reactive oxygen species production after TNFα stimulation. Nicaraven suppressed TNFα-induced mRNA expression of multiple adhesion molecules and pro-inflammatory cytokines, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, MCP-1, TNFα, interleukin-1β (IL-1β), IL-6, and IL-8. In addition, Nicaraven inhibited monocyte adhesion and reduced the protein levels of VCAM-1 and ICAM-1. Mechanistically, Nicaraven prevented TNFα-induced activation of NF-κB signaling pathway by suppressing the phosphorylation of NF-κB p65, IκBα, and IκB kinase (IKK)α/β, stabilizing IκBα, and inhibiting the translocation of p65 from cytosol to nucleus. Finally, we showed that Nicaraven improved the functions of endothelial cells, seen as the upregulation of endothelial nitric oxide synthase and increased nitric oxide levels. Our findings indicated that Nicaraven effectively inhibits TNFα-induced endothelial activation and inflammatory response at least partly through inhibiting NF-κB signaling pathway.

Background: Osteosarcoma was the most common primary bone malignancy in children and adolescents. It was imperative to identify effective prognostic biomarkers for this cancer. This study was aimed to identify potential crucial genes of osteosarcoma by integrated bioinformatics analysis., Methods: Identification of differentially expressed genes from public data gene expression profiles (GSE42352), functional and pathway enrichment analysis, protein-protein interaction (PPI) network construction and module analysis, Cox regression and survival analysis was conducted., Results: Totally 17 co-differential genes were found to be differentially expressed. These genes were enriched in biological processes, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) pathway of inflammatory immune response. PPI network was constructed with 63 differentially expressed genes that co-existed between the test set and the validation set. The area under the receiver operating characteristic curve (AUC value) was 0.855, which indicated that the expression of PODN had a good diagnostic value for osteosarcoma. Furthermore, Cox regression and survival analysis revealed 5 genes were statistically significant., Conclusions: PODN was regarded as a potential biomarker for the diagnosis and prognosis of osteosarcoma, ACTA2, COL6A1, FAP, OLFML2B and COL6A3, can be used as potential prognostic indicators for osteosarcoma., (© 2021. The Author(s).)

Studies showed that the increase of myeloid-derived suppressor cells (MDSCs) in tumour microenvironment is closely related to the resistant treatment and poor prognosis of metastatic breast cancer. However, the effect of tumour-derived exosomes on MDSCs and its mechanism are not clear. Here, we reported that breast cancer cells (4T1)-secreted exosomes (BCC-Ex) were able to differentiate bone marrow cells into MDSCs and significantly inhibited the proliferation of T lymphocytes to provide an immunosuppressive microenvironment for cancer cells in vivo and in vitro. The number of MDSCs in bone marrow and spleen of 4T1 tumour-bearing mice and BCC-Ex infused mice was significantly higher than that of normal mice, whereas the number of T lymphocytes in spleen was significantly decreased. In addition, BCC-Ex markedly promoted the differentiation of MDSCs from bone marrow cells or bone marrow cells derived macrophages, seen as the increased expressions of MDSCs-related functional proteins Arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS). Furthermore, BCC-Ex significantly down-regulated the expressions of chemokine receptor CXCR4 and markedly up-regulated the levels of inflammatory cytokines IL-6 and IL-10 in bone marrow cells and macrophages and remarkably inhibited the division and proliferation of T cells. Importantly, CXCR4 agonist, CXCL12, could reverse the function of BCC-Ex, indicating that BCC-Ex-induced MDSCs might be dependent on the down-regulation of CXCR4. Western blot showed that BCC-Ex significantly promoted the phosphorylation of STAT3 in bone marrow cells, resulting in the inhibitions of the proliferation and apoptosis of bone marrow cells, and the aggravation of the differentiation of bone marrow cells into MDSCs., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: To explore the correlation between the curvature of the cervical spine and the degree of cervical disc bulging in young patients with cervical pain., Methods: The clinical data of 539 young patients with neck pain from January 2015 to December 2018 were retrospectively analyzed. There were 251 males and 288 females, aged 18 to 40 (32.2±6.3) years old. The cervical curvature and cervical disc bulging were measured by cervical X-ray and MRI. According to cervical curvature, the patients were divided into 175 cases of cervical lordosis group (cervical curvature > 7 mm), 163 cases of cervical erection group (0

Precartilaginous stem cells (PCSCs) are able to initiate chondrocyte and bone development. The present study aimed to investigate the role of miR-143 and the underlying mechanisms involved in PCSC proliferation. In a rat growth plate injury model, tissue from the injury site was collected and the expression of miR-143 and its potential targets was determined. PCSCs were isolated from the rabbits' distal epiphyseal growth plate. Cell viability, DNA synthesis, and apoptosis were determined with MTT, BrdU, and flow cytometric analysis, respectively. Real time PCR and western blot were performed to detect the mRNA and protein expression of the indicated genes. Indian hedgehog ( IHH ) was identified as a target gene for miR-143 with luciferase reporter assay. Decreased expression of miR-143 and increased expression of IHH gene were observed in the growth plate after injury. miR-143 mimics decreased cell viability and DNA synthesis and promoted apoptosis of PCSCs. Conversely, siRNA-mediated inhibition of miR-143 led to increased growth and suppressed apoptosis of PCSCs. Transfection of miR-143 decreased luciferase activity of wild-type IHH but had no effect when the 3'-UTR of IHH was mutated. Furthermore, the effect of miR-143 overexpression was neutralized by overexpression of IHH. Our study showed that miR-143 is involved in growth plate behavior and regulates PCSC growth by targeting IHH , suggesting that miR-143 may serve as a novel target for PCSC-related diseases., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Combining Ising-type magnetic anisotropy with collinear magnetic interactions in single-molecule magnets (SMMs) is a significant synthetic challenge. Herein we report a Dy[15-MC Cu -5] (1-Dy) SMM, where a Dy III ion is held in a central pseudo-D 5h pocket of a rigid and planar Cu 5 metallacrown (MC). Linking two Dy[15-MC Cu -5] units with a single hydroxide bridge yields the double-decker {Dy[15-MC Cu -5]} 2 (2-Dy) SMM where the anisotropy axes of the two Dy III ions are nearly collinear, resulting in magnetic relaxation times for 2-Dy that are approximately 200 000 times slower at 2 K than for 1-Dy in zero external field. Whereas 1-Dy and the Y III -diluted Dy@2-Y analogue do not show remanence in magnetic hysteresis experiments, the hysteresis data for 2-Dy remain open up to 6 K without a sudden drop at zero field. In conjunction with theoretical calculations, these results demonstrate that the axial ferromagnetic Dy-Dy coupling suppresses fast quantum tunneling of magnetization (QTM). The relaxation profiles of both complexes curiously exhibit three distinct exponential regimes, and hold the largest effective energy barriers for any reported d-f SMMs up to 625 cm -1 ., (© 2020 Wiley-VCH GmbH.)

Stem cells including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells (ASCs) are able to repair/replace damaged or degenerative tissues and improve functional recovery in experimental model and clinical trials. However, there are still many limitations and unresolved problems regarding stem cell therapy in terms of ethical barriers, immune rejection, tumorigenicity, and cell sources. By reviewing recent literatures and our related works, human amnion-derived stem cells (hADSCs) including human amniotic mesenchymal stem cells (hAMSCs) and human amniotic epithelial stem cells (hAESCs) have shown considerable advantages over other stem cells. In this review, we first described the biological characteristics and advantages of hADSCs, especially for their high pluripotency and immunomodulatory effects. Then, we summarized the therapeutic applications and recent progresses of hADSCs in treating various diseases for preclinical research and clinical trials. In addition, the possible mechanisms and the challenges of hADSCs applications have been also discussed. Finally, we highlighted the properties of hADSCs as a promising source of stem cells for cell therapy and regenerative medicine and pointed out the perspectives for the directions of hADSCs applications clinically.

Background: Autophagy is a highly conserved homeostatic process in the human body that is responsible for the elimination of aggregated proteins and damaged organelles. Several autophagy-related genes (ARGs) contribute to the process of tumorigenesis and metastasis of prostate cancer (PCa). Also, miRNAs have been proven to modulate autophagy by targeting some ARGs. However, their potential role in PCa still remains unclear., Methods: An univariate Cox proportional regression model was used to identify 17 ARGs associated with the overall survival (OS) of PCa. Then, a multivariate Cox proportional regression model was used to construct a 6 autophagy-related prognostic genes signature. Patients were divided into low-risk group and high-risk group using the median risk score as a cutoff value. High-risk patients had shorter OS than low-risk patients. Furthermore, the signature was validated by ROC curves. Regarding mRNA and miRNA, 12 differentially expressed miRNAs (DEMs) and 1073 differentially expressed genes (DEGs) were detected via the GEO database. We found that miR-205, one of the DEMs, was negatively regulated the expression of ARG (NKX2-3). Based on STRING analysis results, we found that the NKX2-3 was moderately related to the part of genes among the 6 autophagy-related genes prognostic signature. Further, NKX 2-3 was significantly correlated with OS and some clinical parameters of PCa by cBioProtal. By gene set enrichment analysis (GSEA). Lastly, we demonstrated that the association between NKX2-3 and tumor mutation burden (TMB) and PDCD1 (programmed cell death 1) of PCa., Results: We identified that the six ARGs expression patterns are independent predictors of OS in PCa patients. Furthermore, our results suggest that ARGs and miRNAs are inter-related. MiR-205 was negatively regulated the expression of ARG (NKX2-3). Further analysis demonstrated that NKX2-3 may be a potential biomarker for predicting the efficacy of anti-PD-1 therapy in PCa., Conclusions: The current study may offer a novel autophagy-related prognostic signature and may identify a promising miRNA-ARG pathway for predicting the efficacy of anti-PD-1 therapy in PCa.

Alfalfa (Medicago sativa L.) is one of the most important and widely cultivated forage crops. It is commonly used as a vegetable and medicinal herb because of its excellent nutritional quality and significant economic value. Based on Illumina, Nanopore and Hi-C data, we assembled a chromosome-scale assembly of Medicago sativa spp. caerulea (voucher PI464715), the direct diploid progenitor of autotetraploid alfalfa. The assembled genome comprises 793.2 Mb of genomic sequence and 47,202 annotated protein-coding genes. The contig N50 length is 3.86 Mb. This genome is almost twofold larger and contains more annotated protein-coding genes than that of its close relative, Medicago truncatula (420 Mb and 44,623 genes). The more expanded gene families compared with those in M. truncatula and the expansion of repetitive elements rather than whole-genome duplication (i.e., the two species share the ancestral Papilionoideae whole-genome duplication event) may have contributed to the large genome size of M. sativa spp. caerulea. Comparative and evolutionary analyses revealed that M. sativa spp. caerulea diverged from M. truncatula ~5.2 million years ago, and the chromosomal fissions and fusions detected between the two genomes occurred during the divergence of the two species. In addition, we identified 489 resistance (R) genes and 82 and 85 candidate genes involved in the lignin and cellulose biosynthesis pathways, respectively. The near-complete and accurate diploid alfalfa reference genome obtained herein serves as an important complement to the recently assembled autotetraploid alfalfa genome and will provide valuable genomic resources for investigating the genomic architecture of autotetraploid alfalfa as well as for improving breeding strategies in alfalfa.

Liver hepatocellular carcinoma (LIHC) is the most prevalent primary cancer of the liver, and immune-related genes (IRGs) regulate its development. So far, there is still no precise biomarker that predicts response to immunotherapy in LIHC. Therefore, this research seeks to identify immunogenic prognostic biomarkers and explore potential predictors for the efficacy of anti-PD-1/PD-L1 therapies in LIHC. The clinical data and gene expression profiles of patients diagnosed with LIHC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Moreover, IRGs were obtained from the ImmPort database. We discovered 35 IRGs that were differentially expressed between LIHC tissues and corresponding normal tissues. Through univariate Cox regression analysis, eight prognostic differentially expressed IRGs (PDEIRGs) were identified. Further, three optimal PDEIRGs (BIRC5, LPA, and ROBO1) were identified and used to construct a prognostic risk signature of LIHC patients via multivariate Cox regression analysis. The signature was validated by ROC curves. Subsequently, based on gene set enrichment analysis (GSEA) analysis, two out of the three optimal PDEIRGs (BIRC5 and LPA) were significantly enriched in the mismatch repair (MMR) pathway. Moreover, the two PDEIRGs (BIRC5 and LPA) were significantly correlated with the expression of genes related to mismatch repair (MLH1, MSH2, MSH6, and PMS2). Furthermore, correlations between the two PDEIRGs (BIRC5 and LPA) and immune checkpoints of cancer treatment (such as CTLA4, PD-1, and PD-L1) were demonstrated. Hyperprogressive disease (HPD) is a novel pattern of tumor progression which has a close relationship with immune checkpoint inhibitors (ICIs) utilization. MDM2 family amplification might promote the HPD phenomenon. Finally, we found a positive regulatory relationship between HPD related gene (MDM2) and BIRC5. Notably, MDM2 can either interact directly with BIRC5 or indirectly via downstream transcription factors of BIRC5. Overall, our study uncovered a novel 3-immune-related prognostic genes in LIHC., (Copyright © 2020 Wu, Quan, Luo, Pan, Peng and Zhang.)

Cellular polarization underlies many facets of cell behavior, including cell growth. The rod-shaped fission yeast Schizosaccharomyces pombe is a well-established, genetically tractable system for studying growth polarity regulation. S. pombe cells elongate at their two cell tips in a cell cycle-controlled manner, transitioning from monopolar to bipolar growth in interphase when new ends established by the most recent cell division begin to extend. We previously identified cytokinesis as a critical regulator of new end growth and demonstrated that Fic1, a cytokinetic factor, is required for normal polarized growth at new ends. Here, we report that Fic1 is phosphorylated on two C-terminal residues, which are each targeted by multiple protein kinases. Endogenously expressed Fic1 phosphomutants cannot support proper bipolar growth, and the resultant defects facilitate the switch into an invasive pseudohyphal state. Thus, phosphoregulation of Fic1 links the completion of cytokinesis to the re-establishment of polarized growth in the next cell cycle. These findings broaden the scope of signaling events that contribute to regulating S. pombe growth polarity, underscoring that cytokinetic factors constitute relevant targets of kinases affecting new end growth.This article has an associated First Person interview with Anthony M. Rossi, joint first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Hepatocellular carcinoma (HCC) is the third leading cause of the cancer-related death in the world. Human amniotic mesenchymal stem cells (hAMSCs) have been characterized with a pluripotency, low immunogenicity and no tumorigenicity. Especially, the immunosuppressive and anti-inflammatory effects of hAMSCs make them suitable for treating HCC. Here, we reported that hAMSCs administrated by intravenous injection significantly inhibited HCC through suppressing cell proliferation and inducing cell apoptosis in tumour-bearing mice with Hepg2 cells. Cell tracking experiments with GFP-labelled hAMSCs showed that the stem cells possessed the ability of migrating to the tumorigenic sites for suppressing tumour growth. Importantly, both hAMSCs and the conditional media (hAMSC-CM) have the similar antitumour effects in vitro, suggesting that hAMSCs-derived cytokines might be involved in their antitumour effects. Antibody array assay showed that hAMSCs highly expressed dickkopf-3 (DKK-3), dickkopf-1 (DKK-1) and insulin-like growth factor-binding protein 3 (IGFBP-3). Furthermore, the antitumour effects of hAMSCs were further confirmed by applications of the antibodies or the specific siRNAs of DKK-3, DKK-1 and IGFBP-3 in vitro. Mechanically, hAMSCs-derived DKK-3, DKK-1 and IGFBP-3 markedly inhibited cell proliferation and promoted apoptosis of Hepg2 cells through suppressing the Wnt/β-catenin signalling pathway and IGF-1R-mediated PI3K/AKT signalling pathway, respectively. Taken together, our study demonstrated that hAMSCs possess significant antitumour effects in vivo and in vitro and might provide a novel strategy for HCC treatment clinically., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

In the fission yeast Schizosaccharomyces pombe , both RNAi machinery and RNAi-independent factors mediate transcriptional and posttranscriptional silencing and heterochromatin formation. Here, we show that the silencing of reporter genes at major native heterochromatic loci (centromeres, telomeres, mating-type locus and rDNA regions) and an artificially induced heterochromatin locus is alleviated in a fission yeast hsp90 mutant, hsp90-G84C Also, H3K9me2 enrichment at heterochromatin regions, especially at the mating-type locus and subtelomeres, is compromised, suggesting heterochromatin assembly defects. We further discovered that Hsp90 is required for stabilization or assembly of the RNA-induced transcriptional silencing (RITS) and Argonaute siRNA chaperone (ARC) RNAi effector complexes, the RNAi-independent factor Fft3, the shelterin complex subunit Poz1 and the Snf2/HDAC-containing repressor complex (SHREC). Our ChIP data suggest that Hsp90 regulates the efficient recruitment of the methyltransferase/ubiquitin ligase complex CLRC by shelterin to chromosome ends and targeting of the SHREC and Fft3 to mating type locus and/or rDNA region. Finally, our genetic analyses demonstrated that increased heterochromatin spreading restores silencing at subtelomeres in the hsp90-G84C mutant. Thus, this work uncovers a conserved factor critical for promoting RNAi-dependent and -independent heterochromatin assembly and gene silencing through stabilizing multiple effectors and effector complexes., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Background: Ginkgolide B (GKB) is a major active component of the extracts of Ginkgo biloba leaves, and it has been used as an anti-cancer agent. However, it is unknown whether GKB has the therapeutic effects on lung cancer. Here, we studied the effects of GKB on lung cancer cells., Methods: The effects of GKB on lung cancer cell proliferation and invasion were analyzed by cell counting kit (CCK-8) and cell invasion assays, respectively. Apoptosis was detected by flow cytometry. Western blot analysis was used to confirm the expression of autophagy-associated proteins in GKB-treated cells. Immunofluorescence analysis was used to analyze the level of light chain 3B (LC3B)., Results: Treatment with GKB time-dependently inhibited the proliferation and decreased the invasive capacity of A549 and H1975 cells. GKB induced apoptosis of these cells, but there was no significant effect on apoptosis compared to the control treatment. GKB-induced inhibition of cell proliferation and GKB-induced cell death were due to autophagy rather than apoptosis. GKB-induced autophagy of lung cancer cells was dependent on beclin-1, and autophagy-induced inhibition of the NLRP3 inflammasome contributed to the anti-tumor effect of GKB., Conclusions: GKB-mediated autophagy of lung cancer cells is beclin-1-dependent and results in inhibition of the NLRP3 inflammasome. Therefore, GKB might be a potential therapeutic candidate for the treatment of lung cancer.

Precartilaginous stem cells (PCSCs) are adult stem cells that can initiate chondrocytes and bone development. In the present study, we explored whether miR-132/212 was involved in the proliferation of PCSCs via Hedgehog signaling pathway. PCSCs were isolated and purified with the fibroblast growth factor receptor-3 (FGFR-3) antibody. Cell viability, DNA synthesis and apoptosis were measured using MTT, BrdU and flow cytometric analysis. The mRNA and protein expression were detected by real-time PCR and Western blot, respectively. The target gene for miR-132/212 was validated by luciferase reporter assay. Results showed that transfection with miR-132/212 mimic significantly increased cell viability and DNA synthesis, and inhibited apoptosis of PCSCs. By contrast, miR-132/212 inhibitor could suppress growth and promote apoptosis of PCSCs. Luciferase reporter assays indicated that transfection of miR-132/212 led to a marked reduction of luciferase activity, but had no effect on PTCH1 3'-UTR mutated fragment, suggesting that Patched1 (PTCH1) is a target of miR-132/212. Furthermore, treatment with miR-132/212 mimics obviously increased the protein expression of Indian hedgehog (Ihh) and parathyroid hormone related protein (PTHrP), which was decreased after treatment with Hedgehog signaling inhibitor, cyclopamine. We also found that inhibition of Ihh/PTHrP signaling by cyclopamine significantly suppressed growth and DNA synthesis, and induced apoptosis in PCSCs. These findings demonstrate that miR-132/212 promotes growth and inhibits apoptosis in PCSCs by regulating PTCH1-mediated Ihh/PTHrP pathway, suggesting that miR-132/212 cluster might serve as a novel target for bone diseases., (© 2020 The Author(s).)

Background: New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a member of the cancer testis antigen family. NY-ESO-1 has documented potential as an effective target for cancer immunotherapy. The prognostic value of NY-ESO-1 expression in solid tumors, however, remains controversial because of inconclusive data., Methods: For this analysis, the Medline, Embase, and Cochrane Library databases were searched up to February 2018 for studies investigating NY-ESO-1 expression in solid tumors and overall survival (OS), progression-free survival (PFS), or disease-free survival (DFS). Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted from each study. Pooled HRs and CIs were calculated using the Mantel-Haenszel fixed effects or random effects model., Results: A total of 23 studies were included in the analysis. The combined HR (95% CI) estimates for OS, PFS, and DFS were 1.41 (95% CI: 1.24-1.61; I = 0%), 1.62 (95% CI: 1.42-1.84; I = 17%), and 0.95 (95% CI: 0.56-1.59; I = 57%), respectively., Conclusions: NY-ESO-1 expression in solid tumors is associated with worse OS and PFS. Studies are still needed to provide more evidence.

Volatile compounds in flowers of Rhododendron delavayi , R. agastum , R. annae , and R. irroratum were analyzed using comprehensive two-dimensional gas chromatography-mass spectrometry (GC×GC) coupled with high-resolution quadrupole time-of-flight mass spectrometry (QTOFMS). A significantly increased number of compounds was separated by GC×GC compared to conventional one-dimensional GC (1DGC), allowing more comprehensive understanding of the volatile composition of Rhododendron flowers. In total, 129 volatile compounds were detected and quantified. Among them, hexanal, limonene, benzeneacetaldehyde, 2-nonen-1-ol, phenylethyl alcohol, citronellal, isopulegol, 3,5-dimethoxytoluene, and pyridine are the main compounds with different content levels in all flower samples. 1,2,3-trimethoxy-5-methyl-benzene exhibits significantly higher content in R. irroratum compared to in the other three species, while isopulegol is only found in R. irroratum and R. agastum .

Background: Increasing evidence has shown that mesenchymal stem cells (MSCs) yield a favorable therapeutic benefit for thermal burn skin wounds. Human amniotic MSCs (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential which makes them suitable for treating skin wounds. However, the exact effects of hAMSCs on the healing of thermal burn skin wounds and their potential mechanisms are not explored., Methods: hAMSCs were isolated from amniotic membrane and characterized by RT-PCR, flow cytometry, immunofluorescence, and tumorigenicity test. We assessed the effects of hAMSCs and hAMSC conditional medium (CM) on wound healing in a deep second-degree burn injury model of mice. We then investigated the biological effects of hAMSCs and hAMSC-CM on the apoptosis and proliferation of heat stress-injured human keratinocytes HaCAT and dermal fibroblasts (DFL) both in vivo and in vitro. Next, we explored the underlying mechanisms by assessing PI3K/AKT and GSK3β/β-catenin signaling pathways in heat injured HaCAT and DFL cells after hAMSCs and hAMSC-CM treatments using PI3K inhibitor LY294002 and β-catenin inhibitor ICG001. Antibody array assay was used to identify the cytokines secreted by hAMSCs that may activate PI3K/AKT signaling pathway., Results: Our results showed that hAMSCs expressed various markers of embryonic stem cells and mesenchymal stem cells and have low immunogenicity and no tumorigenicity. hAMSC and hAMSC-CM transplantation significantly promoted thermal burn wound healing by accelerating re-epithelialization with increased expression of CK19 and PCNA in vivo. hAMSCs and hAMSC-CM markedly inhibited heat stress-induced apoptosis in HaCAT and DFL cells in vitro through activation of PI3K/AKT signaling and promoted their proliferation by activating GSK3β/β-catenin signaling. Furthermore, we demonstrated that hAMSC-mediated activation of GSK3β/β-catenin signaling was dependent on PI3K/AKT signaling pathway. Antibody array assay showed that a panel of cytokines including PAI-1, C-GSF, periostin, and TIMP-1 delivered from hAMSCs may contribute to the improvement of the wound healing through activating PI3K/AKT signaling pathway., Conclusion: Our results demonstrated that hAMSCs and hAMSC-CM efficiently cure heat stress-induced skin injury by inhibiting apoptosis of skin cells and promoting their proliferation through activating PI3K/AKT signaling pathway, suggesting that hAMSCs and hAMSC-CM may provide an alternative therapeutic approach for the treatment of skin injury.

Although great achievements have been made in the synthesis of giant lanthanide clusters, novel structural models are still scarce. Herein, we report a giant lanthanide cluster Dy 76 , constructed from [Dy 3 (μ 3 -OH) 4 ] and [Dy 5 (μ 4 -O)(μ 3 -OH) 8 ] building blocks. As the largest known Dy cluster, the structure of Dy 76 can be seen as arising from the fusion of two Dy 48 clusters; these clusters can be isolated under various synthetic conditions and were characterized by single-crystal X-ray diffraction. This new, fused structural model of the pillar motif has not been found in Ln clusters. Furthermore, the successful conversion of Dy 76 back into Dy 48 in a retrosynthetic manner supports the proposed fusion formation mechanism of Dy 76 . Electrospray ionization mass spectrometry (ESI-MS) analysis suggests that the metal cluster skeleton of Dy 76 shows good stability in various solvents. This work not only reveals a new structural type of Ln clusters but also provides insight into the novel fusion assembly process., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bread wheat (AABBDD) originated from the diploid progenitor Triticum urartu (AA), a relative of Aegilops speltoides (BB), and Ae. tauschii (DD). The DREB1 transcriptional factor plays key regulatory role in low-temperature tolerance. The modern breeding strategies resulted in serious decrease of the agricultural biodiversity, which led to a loss of elite genes underlying abiotic stress tolerance in crops. However, knowledge of this gene's natural diversity is largely unknown in the genome donor species of wheat. We characterized the dehydration response element binding protein 1 (DREB1) gene-diversity pattern in Ae. speltoides, Ae. tauschii, T. monococcum and T. urartu. The highest nucleotide diversity value was detected in Ae. speltoides, followed by Ae. tauschii and T. monococcum. The lowest nucleotide diversity value was observed in T. urartu. Nucleotide diversity and haplotype data might suggest no reduction of nucleotide diversity during T. monococcum domestication. Alignment of the 68 DREB1 sequences found a large-size (70 bp) insertion/deletion in the accession PI486264 of Ae. speltoides, which was different from the copy of sequences from other accessions of Ae. speltoides, suggesting a likely existence of two different ancestral Ae. speltoides forms. Implication of sequences variation of Ae. speltoides on origination of B genome in wheat was discussed., Competing Interests: This manuscript or substantial parts of it, submitted to the journal has not be under consideration by any other journal. No material submitted as part of a manuscript infringes existing copyrights, or the rights of a third party. All authors have approved the manuscript. The authors have declared that no competing interests exist.

Human menstrual blood-derived stem cells (hMBSCs) are a novel type of mesenchymal stem cells (MSCs) that have a high proliferative rate, multilineage differentiation potential, low immunogenicity, and low oncogenicity, making them suitable candidates for regenerative medicine. The therapeutic efficacy of hMBSCs has been demonstrated in some diseases; however, their effects on cervical cancer remain unclear. In the present study, we investigated whether hMBSCs have anticancer properties on cervical cancer cells in vivo and in vitro, which has not yet been reported. In vitro, transwell coculturing experiments revealed that hMBSCs suppress the proliferation and invasion of HeLa cervical cancer cells by inducing G0/G1 cell cycle arrest. In vivo, we established a xenografted BALB/c nude mouse model by subcutaneously coinjecting HeLa cells with hMBSCs for 21 days. We found that hMBSCs significantly decrease the average volume and average weight of xenografted tumors. ELISA, TGF- β 1 antibody, and recombinant human TGF- β 1 (rhTGF- β 1) were used to analyze whether TGF- β 1 contributed to cell cycle arrest. We found that hMBSC-secreted TGF- β 1 and rhTGF- β 1 induced cell cycle arrest and increased the expression of phospho-JNK and phospho-P21 in HeLa cells, which was mostly reversed by TGF- β 1 antibody. These results indicate that hMBSCs have antitumor properties on cervical cancer in vitro and in vivo, mediated by the TGF- β 1/JNK/p21 signaling pathway. In conclusion, this study suggests that hMBSC-based therapy is promising for the treatment of cervical cancer.

A 3d-4f heterometallic metallacrown with formula of [EuCu 5 (quinha) 5 (sal) 2 (py) 5 ]CF 3 SO 3 ·py·3H 2 O (1) (H 2 quinha = quinaldichydroxamic acid; Hsal = salicylaldehyde) has been synthesized. This complex shows field-induced slow magnetic relaxation via a Raman-like process, where studies of the isostructural {LuCu 5 } (2) and {YCu 5 } (3) complexes show that the slow dynamics mainly arise from the {Cu 5 } S = 1/2 ground state rather than the Eu III ion. However, the Eu III ion enhances the relaxation rates of the {Cu 5 } unit which likely arises from second-order effects in the formally diamagnetic 7 F 0 ground state of Eu III .

Although naloxone has been documented to exert neuroprotection in animal model of cerebral ischemia, the mechanism is not well understood. In this present study we investigated whether naloxone affected the mitochondrial apoptotic pathway in ischemic brain injury of rats. SD rats were subjected to a permanent middle cerebral artery occlusion surgery, and received naloxone (0.5, 1, 2 mg/kg, i.v.) immediately after ischemia. Neurological deficits were evaluated 24 h after ischemia using the McGraw Stroke Index, and then the rats were killed, and the brains were collected for further analyses. We show that naloxone treatment dose-dependently decreased the infarction volume and morphological injury, improved motor behavioral function, and markedly curtailed brain edema. Furthermore, naloxone administration significantly inhibited the nuclear translocation of NF-κB p65 and decreased the levels of nuclear NF-κB p65 in the ischemic penumbra. Naloxone administration also dose-dependently increased the NF-κB inhibitory protein (IκBα) levels and attenuated phosphorylated NIK and IKKα levels in the ischemic penumbra. In addition, naloxone administration dose-dependently increased Bcl-2 levels, decreased Bax levels, stabilized the mitochondrial transmembrane potential, and inhibited cytochrome c release and caspase 3 and caspase 9 activation. These results indicate that the neuroprotective effects of naloxone against ischemic brain injury involve the inhibition of NF-κB activation via the suppression of the NIK/IKKα/IκBα pathway and the obstruction of the mitochondrial apoptotic pathway in neurons.