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To better understand the ecological effects of mariculture, the diversity distribution, determinant and interaction of microeukaryote communities from fish cage and suspended shellfish farming were investigated in three bays of South China Coast. Our alpha and beta diversity analyses showed that the difference of the microeukaryote community between fish and shellfish farming was more significant at local than regional scale, and microeukaryotes respond more to spatial effect than mariculture effect at regional scale. Mantel test, variation partitioning analysis and co-occurrence network analysis revealed that the environmental factors especially chemical and biotic factors contributed more to community assembly in fish than shellfish farming. Based on the comparisons of community composition and determinant between fish and shellfish farming, the effect mechanisms of the two farming types on microeukaryote community were proposed. Fish farming brings significant environmental variation and thus has strong bottom-up impacts on microeukaryotes, while shellfish farming exerts a grazing pressure on microeukaryotes by filter-feeding and has top-down control to them. Furthermore, the network stability analyses revealed weaker community stability in fish than shellfish farming, suggesting that the microeukaryote community was more sensitive to environmental change deduced by fish than shellfish farming. Overall, this study revealed the different influencing mechanisms of fish and shellfish mariculture on microeukaryotes, which will improve the understanding of the ecological effects of mariculture and provide guidance for the management of mariculture under future environmental pressures. [Display omitted] • Effects of mariculture on microeukaryotic community was more significant at local than regional scale. • Chemical and biotic factors contributed more to community assembly in fish than shellfish farming. • Fish farming had strong bottom-up impacts on microeukaryotic community; Shellfish farming exerted top-down control to them. • Microeukaryote community was more sensitive to environmental change deduced by fish than shellfish farming. • Management practices and ecological remediation should be carried out in principle of adaptation to mariculture types. [ABSTRACT FROM AUTHOR]

LncRNAs are widely involved in various biological processes of plants. Recent evidences indicated that lncRNAs could act as competing endogenous RNAs (ceRNAs) to adsorb complementary miRNAs in a type of target mimicry, thereby indirectly regulating the target genes of miRNAs. In this study, a lncRNA, lncRNA08489 was identified to be the ceRNA of miR482e-3p in tomato plants. The expression patterns of lncRNA08489 and miR482e-3p showed opposite trends after tomato plants infected with Phytophthora infestans. In tomato leaves overexpressing lncRNA08489 (OE08489), the expression level of miR482e-3p decreased and its target gene, NBS-LRR increased. After infection with P. infestans , the resistance of OE08489 plants was stronger than that of the wild type, and the reactive oxygen species (ROS) scavenging ability of OE08489 plants was significantly improved. Taken together, these results indicated that lncRNA08489 acted as a ceRNA to decoy miR482e-3p and regulate the expression of NBS-LRR to enhance tomato resistance through ROS-scavenging system. • LncRNA08489 modulated the accumulation of NBS-LRR through decoying miR482e-3p. • LncRNA08489 acted as a positive regulator of tomato resistance to Phytophthora infestans infection. • Overexpressing lncRNA08489 tomato increased the ROS-scavenging. [ABSTRACT FROM AUTHOR]

The role of bioactive peptides in diabetes management has attracted extensive attention. In this study, the 1–3 kDa fraction of rice bran peptides (RBPs) was obtained by the hydrolysis of alkaline and dispase, and the following ultrafiltration demonstrated excellent α-glucosidase inhibition activity with an IC 50 value of 1.17 ± 0.08 mg/mL and exhibited postprandial hypoglycemic activity in vivo. Enzymatic kinetics studies revealed that RBPs (1–3 kDa) inhibited α-glucosidase via competitive inhibition. Thirty-two peptides were characterized from RBPs (1–3 kDa) by LC-MS/MS. Virtual screening was applied to screening the new potential α-glucosidase inhibitor, and NVEKKDPTGA (NA-10) with a binding energy of −10.24 kcal/mol to α-glucosidase was selected as the most promising peptide. Molecular docking reflected that Ala at the C-terminal and KK amino acid cluster play a key role in forming hydrogen bonds with the catalytic site of α-glucosidase, which might be critical for the α-glucosidase inhibitory effect. This study proved that RBPs could be a promising bio-factor food ingredient for diabetes prevention. 1–3 kDa fraction of rice bran peptides showed the best α-glucosidase inhibition activity with an IC 50 value of 1.17 ± 0.08 mg/mL and exhibited hypoglycemic effect on maltose tolerance test in mice. Molecular docking results revealed that Ala at C-terminal and KK amino acid cluster in rice bran peptides play a key role in its α-glucosidase inhibition activity. Rice bran peptides would be a promising factor to inhibit α-glucosidase. [Display omitted] • 1–3 kDa (1.17 ± 0.08 mg/mL) fraction showed the best α-glucosidase inhibition activity. • Rice bran peptides exhibited hypoglycemic effect on maltose tolerance test in mice. • Ala at C-terminal and KK amino acid cluster play a key role. [ABSTRACT FROM AUTHOR]

Angiogenesis plays a vital role in tumor progression and metastasis. To better understand the role of anesthesia in tumor biology, we previously reported that bupivacaine displayed the inhibitory effects in endothelial cells. In this work, we demonstrated that fentanyl, an opioid medication commonly used in cancer patients, stimulated tumor angiogenesis. We found that fentanyl at nanomolar concentrations significantly stimulated capillary network formation of human lung tumor-associated endothelial cell (HLT-EC) in a similar manner as vascular endothelial growth factor (VEGF), and furthermore that the stimulatory effect of fentanyl was mainly involved in early stage of HLT-EC vascular structure assembly. Particularly, fentanyl significantly increased HLT-EC growth and migration. Fentanyl also protected HLT-EC from apoptosis induced by growth factor withdrawal. In contrast, the same concentrations of fentanyl did not affect human lung cancer cell growth and survival. Fentanyl stimulated migration of some but not all tested human lung cancer cells. Mechanism analysis suggested that fentanyl activates multiple pro-angiogenic signaling pathways, including VEGFR2/FAK/PI3K/Akt and small GTPases. Our work systematically demonstrates that fentanyl stimulates tumor angiogenesis via activating multiple pro-angiogenic signaling pathways. Our findings highlight the potential adverse effect of fentanyl in cancer patients. • Fentanyl stimulates early stage of lung tumor angiogenesis. • Fentanyl increases HLT-EC migration, growth and survival. • Fentanyl activates VEGFR2/FAK, small GTPases and PI3K/Akt in HLT-EC. • Fentanyl increases lung cancer cell migration but not proliferation. [ABSTRACT FROM AUTHOR]

Mitochondria are dynamically regulated by fission and fusion processes. Silibinin induces apoptosis of MCF-7 and MDA-MB-231 human breast cancer cells. However, whether or not mitochondria dysfunction is involved in the apoptosis induction with silibinin of both types of the cells remains unknown. We here report that silibinin decreases the mitochondrial mass in terms of MitoTracker Green staining in both breast cancer cells. Silibinin induces morphological changes of mitochondria from oval to truncated or fragmented shapes accordingly. Condensed crests are observed in mitochondria by transmission electron microscopy. Silibinin causes mitochondrial membrane potential reduced. The expression of mitochondrial fission-associated proteins including dynamin-related protein 1 (DRP1) is up-regulated, whereas expression of the mitochondrial fusion-associated proteins, optic atrophy 1 and mitofusin 1, is down-regulated. In addition, silibinin treatment down-regulates ATP content as well as the levels of mitochondrial biogenesis-regulators including mitochondrial transcription factor A, peroxisome proliferator-activated receptor gamma coactivator 1 and nuclear respiratory factor 2. Moreover, treatments with DRP1 inhibitor, mdivi-1, or with DRP1-targetted siRNA efficiently prevent silibinin-induced apoptosis in the breast cancer cells, whereas inhibition of DRP1 phosphorylation with staurosporine increases apoptosis furthermore. Taken together, we conclude that silibinin impairs mitochondrial dynamics and biogenesis, leading to apoptosis of MCF-7 and MDA-MB-123 cells. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides and antibacterial nanostructures are two emerging classes of antimicrobial agents that differ from conventional small-molecule antibiotics. Combining these two types of antimicrobial agents into one entity may be an effective strategy to improve their antimicrobial efficiency. In this study, we demonstrated an effective antibacterial hybrid formed by covalently conjugating antibacterial gold nanoclusters (Au NCs, a novel antimicrobial nanostructure) and daptomycin (Dap, a cyclic lipopeptide antimicrobial peptide). The as-synthesized hybrid structure (Dap−Au NCs) not only inherits the intrinsic properties from both agents but also renders an enhanced synergistic effect. Compared with the physically mixed Au NCs and daptomycin (Dap+Au NCs), the Dap−Au NCs hybrid structure has a stronger bactericidal effect toward methicillin-resistant Staphylococcus aureus , a representative of multidrug-resistant bacteria. Dap−Au NCs could effectively disrupt bacterial membranes by creating more and/or larger holes in the membranes due to the localized daptomycin within the conjugated structure. These larger (and possibly more) holes motivate the entry of Dap−Au NCs into bacterial cells and lead to more serious damage of the bacteria at subcellular levels. Moreover, bacterial genomic DNA fragmentation was further quantified to show that Dap−Au NCs may induce severe DNA breaks. The strong DNA destruction benefited from localized high concentrations of reactive oxygen species (ROS) induced by the localization of Au NCs in the antimicrobial conjugation. The conjugated Au NCs could serve as a critical free radical generator to continuously produce ROS within the bacteria. The continuous ROS bombings also limit the capacity of the bacteria to develop drug resistance. In addition, a significant fluorescence enhancement of the hybrid structure was observed due to a novel aggregation-induced emission (AIE) pattern caused by the Au NCs and daptomycin conjugation. This conjugation strategy provides a new perspective for the synthesis of new antimicrobial agents as well as AIE-type fluorescence materials. [ABSTRACT FROM AUTHOR]

SlmiR482e-3p is involved in tomato– Phytophthora infestans interactions. In this study, we evaluated the function of the complementary strand slmiR482e-5p. In transgenic plants slMIR482e , slmiR482e-3p, and slmiR482e-5p overexpression increased susceptibility to P. infestans infection, while slmiR482e-3p and slmiR482e-5p silencing increased resistance. Additionally, sllncRNA39298 inhibited slmiR482e-5p expression and increased resistance to P. infestans. Upon P. infestans infection, reactive oxygen species accumulation was higher in leaves overexpressing slMIR482e , slmiR482e-3p, and slmiR482e-5p and lower in sllncRNA39298-overexpressing leaves than in wild-type leaves. These results support the functional importance of complementary strand miRNAs and reveal the roles of slmiR482e-5p and sllncRNA39298 in tomato disease resistance. • miR482e-5p and miR482e-3p coordinately regulate tomato resistance to P. infestans. • lncRNA39298 enhances tomato resistance to P. infestans by decoying miR482e-5p. • miR482e-3p, miR482e-5p, and lncRNA39298 regulate ROS scavenging in tomato. [ABSTRACT FROM AUTHOR]

Abstract: Ultraviolet B (UVB) from sunlight is a major cause of cutaneous lesion. Silibinin, a traditional hepatic protectant, elicits protective effects against UVB-induced cellular damage. In A431 cells, the insulin-like growth factor-1 receptor (IGF-1R) was markedly up-regulated by UVB irradiation. The activation of the IGF-1R signalling pathways contributed to apoptosis of the cells rather than rescuing the cells from death. Up-regulated IGF-1R stimulated downstream mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinases (JNK) and extracellular signal-regulated protein kinases 1/2 (ERK1/2). The subsequent activation of caspase-8 and caspase-3 led to apoptosis. The activation of IGF-1R signalling pathways is the cause of A431 cell death. The pharmacological inhibitors and the small interfering RNA (siRNA) targeting IGF-1R suppressed the downstream activation of JNK/ERK-caspases to help the survival of the UVB-irradiated A431 cells. Indeed, silibinin treatment suppressed the IGF-1R-JNK/ERK pathways and thus protected the cells from UVB-induced apoptosis. [Copyright &y& Elsevier]

Abstract: Mitogen activated protein kinase (MAPK) signal transduction pathways are ubiquitous among eukaryotic organisms with evolutionary conserved modules. Although generally classified as osmotic and cell wall integrity pathways, functional divergences have been observed for HOG1- and SLT2-related MAPK pathways. Here we show that the osmotic signal transduction cascade is involved in cell wall integrity in the phytopathogenic ascomycete Botrytis cinerea. The deletion mutants of the upstream histidine kinase Bos1 and of the MAPK Sak1 showed modified tolerance to cell wall degrading enzymes and cell wall interfering agents, as well as increased staining of β1-3 glucan and chitin compared to the wild-type. The Sak1 MAPK was phosphorylated upon cell wall challenging. Sak1 interfered with the phosphorylation status of the SLT2 type MAPK Bmp3 hinting to cross talk between both MAPK pathways. All signal transduction components interfered with the expression of melanin biosynthesis genes in dark and bright, suggesting a coordinated control of melanin biosynthesis. [Copyright &y& Elsevier]

Abstract: In filamentous ascomycetes, HOG-like signal transduction cascades are involved in the resistance to hyper-osmotic conditions and to dicarboximides and phenylpyrroles. The histidine kinase (HK) Bos1 and the mitogen-activated protein kinase (MAPK) Sak1 are important for the adaptation to hyper-osmotic and oxidative stress, development, and pathogenicity in the phytopathogenic fungus Botrytis cinerea. However, bos1Δ and sak1Δ mutants created previously, also presented different phenotypes, especially the sak1Δ mutants were not resistant to high fungicide concentrations. Since both single mutants were constructed in different parental strains, phenotypic variations due to the genetic background might be suspected. In order to establish the relationship between both protein kinases, we analyzed Sak1 phosphorylation under the control of the Bos1 HK and we realized epistasis analysis between bos1Δ and sak1Δ mutations through the construction of isogenic single and double mutants. Our results show that Bos1 negatively regulates Sak1 phosphorylation and that Bos1 regulates certain phenotypes independently of Sak1. They include fungicide susceptibility, adaptation and conidiation on high neutral osmolarity. [Copyright &y& Elsevier]

Our previous studies showed that silibinin promoted activation of caspases to induce apoptosis in human breast cancer MCF-7 cells by down-regulating the protein expression level of estrogen receptor (ER) α and up-regulating ERβ. Recently, it has been reported that silibinin-induced apoptosis also involved nuclear translocation of apoptosis-inducing factor (AIF). Here we report that silibinin induces nuclear translocation of AIF through the down-regulation of ERα and up-regulation of ERβ in a concentration dependent manner in MCF-7 cells. AIF knockdown with siRNA significantly reverses silibinin-induced apoptosis. The nuclear translocation of AIF is enhanced by treatment with MPP, an ERα antagonist, and blocked with PPT, an ERα agonist. In contrast to ERα activity, the nuclear AIF is increased with an ERβ agonist, DPN and blocked with an ERβ antagonist, PHTPP. Autophagy, negatively regulated by ERα, positively controls AIF-mediated apoptosis, as evidenced by the preventive effect of autophagy inhibitor 3-MA and siRNA targeting LC3, on the nuclear translocation of AIF and cell death induced by silibinin co-treatment with or without MPP. In sum we conclude that AIF in nuclei is involved in silibinin-induced apoptosis, and the nuclear translocation of AIF is increased by down-regulated ERα pathway and/or up-regulated ERβ pathway in MCF-7 cells, accompanying up-regulation of autophagy. Image 1 • Silibinin induces apoptosis-inducing factor-dependent apoptosis in MCF-7 cells. • Estrogen receptor α reduced by silibinin inhibits AIF nuclear translocation. • Estrogen receptor β increased by silibinin promotes AIF nuclear translocation. • Autophagy under the negative control of estrogen receptor α increases nuclear AIF. [ABSTRACT FROM AUTHOR]

The pilot study aims to evaluate the effectiveness and safety of baricitinib in Behcet's Disease (BD) patients with refractory vascular involvement. We consecutively enrolled vascular/cardiac BD patients who received baricitinib (2 mg/day) along with glucocorticoids (GCs) and immunosuppressants in our center. Efficacy assessment mainly depends on the proportion of clinical remission and side effects were recorded. 17 patients (12 males) were included with a mean follow-up of 10.7 ± 5.3 months. At 3 months of follow-up, 76.5% of patients achieved a complete response and the proportion increased to 88.2% at the last visit. During follow-up, ESR (p < 0.01) and hsCRP (p < 0.0001) decreased significantly, as well as Behçet's Disease Current Activity Form score (p < 0.01). In addition, baricitinib showed a GCs-sparing effect. No serious adverse events were noted. Our study suggests that baricitinib is well-tolerated and effective in treating refractory vascular/cardiac BD patients. • New treatments are warranted for refractory vascular BD patients due to its high mortality and poor clinical prognosis. • Baricitinib appeared to be potentially effective and well-tolerated in refractory vascular BD patients. • Baricitinib had a glucocorticoid-sparing effect on refractory vascular BD. [ABSTRACT FROM AUTHOR]

This paper presents a novel signal processing scheme, namely morphological convolution operator (MCO) lifted morphological undecimated wavelet (MUDW), for rolling element bearing fault detection. In this scheme, a MCO is first designed to fully utilize the advantage of the closing & opening gradient operator and the closing–opening & opening–closing gradient operator for feature extraction as well as the merit of excellent denoising characteristics of the convolution operator. The MCO is then introduced into MUDW for the purpose of improving the fault detection ability of the reported MUDWs. Experimental vibration signals collected from a train wheelset test rig and the bearing data center of Case Western Reserve University are employed to evaluate the effectiveness of the proposed MCO lifted MUDW on fault detection of rolling element bearings. The results show that the proposed approach has a superior performance in extracting fault features of defective rolling element bearings. In addition, comparisons are performed between two reported MUDWs and the proposed MCO lifted MUDW. The MCO lifted MUDW outperforms both of them in detection of outer race faults and inner race faults of rolling element bearings. [ABSTRACT FROM AUTHOR]

Ultraviolet B (UVB) irradiation causes skin inflammation and apoptosis. Mitochondria are highly dynamic and undergo constant fusion and fission that are essential for maintaining physiological functions of cells. Although dysfunction of mitochondria has been implicated in skin damages, little is known about the roles of mitochondrial dynamics in these processes. UVB irradiation increases abnormal mitochondrial content but decreases mitochondrial volume in immortalized human keratinocyte HaCaT cells. UVB irradiation resulted in marked upregulation of mitochondrial fission protein dynamin-related protein 1 (DRP1) and downregulation of mitochondrial outer membrane fusion proteins 1 and 2 (MFN1 and MFN2) in HaCaT cells. Mitochondrial dynamics was discovered to be crucial for NLRP3 inflammasome and cGAS-STING pathway activation, as well as the induction of apoptosis. Inhibition of mitochondrial fission by treatments with a DRP1 inhibitor, mdivi-1, or with DRP1-targeted siRNA, efficiently prevented UVB-induced NLRP3/cGAS-STING mediated pro-inflammatory pathways or apoptosis in the HaCaT cells, whereas inhibition of mitochondrial fusion with MFN1and 2 siRNA increased these pro-inflammatory pathways or apoptosis. The enhanced mitochondrial fission and reduced fusion caused the up-regulation of reactive oxygen species (ROS). Application of an antioxidant, N -acetyl- l -cysteine (NAC), which scavenges excessive ROS, attenuated inflammatory responses through suppressing NLRP3 inflammasome and cGAS-STING pathway activation, and rescued cells from apoptosis caused by UVB-irradiation. Together, our findings revealed the regulation of NLRP3/cGAS-STING inflammatory pathways and apoptosis by mitochondrial fission/fusion dynamics in UVB-irradiated HaCaT cells, providing a new strategy for the therapy of UVB skin injury. [Display omitted] • UVB perturbs mitochondrial fission/fusion dynamics in HaCaT cells. • Disturbed mitochondrial dynamics control the amount of mitochondria. • Disturbed mitochondrial dynamics regulate NLRP3/cGAS-STING mediated pro-inflammatory pathways and apoptosis. • ROS are responsible for pro-inflammatory pathways and apoptosis initiated by the dysregulated mitochondrial dynamics. [ABSTRACT FROM AUTHOR]

Ultraviolet B (UVB) irradiation causes skin damages. In this study, we focus on the involvement of mitochondrial disorders in UVB injury. Surprisingly, UVB irradiation increases the amounts of mitochondria in human immortalized keratinocytes HaCaT. However, further analysis shows that ATP levels decreased by UVB treatment in accordance with the collapse of mitochondrial membrane potential (MMP), suggesting an accumulation of dysfunctional mitochondria in UVB-irradiated HaCaT cells. Mitophagy, mainly mediated by PINK1 and parkin, is critical for the elimination of damaged mitochondria. Western blot results show that the levels of both PINK1 and parkin are decreased in UVB-irradiated cells, indicating the impairment of mitophagy. Silencing the expression of PINK1 or parkin by transfection of siRNA shows essentially the same damage to the cells as UVB irradiation does, including increased mitochondrial amount, decreased MMP and ATP production, and enhanced apoptosis, evidencing that repression of PINK1/parkin-mediated mitophagy plays a primary cause of UVB-caused cells damages. We previously found that HaCaT cells exposed to UVB showed activation of the cGAS-STING pathway and apoptosis. Here, silencing PINK1 or parkin also increases the protein levels of cGAS and STING, facilitates nuclear accumulation of NF-κB, and promotes the transcription of IFNβ, suggesting for the activation of STING pathway. Mitophagy impairment either by UVB-irradiation or by PINK1/parkin silencing initiates caspase-3-mediated apoptosis, as shown by the activation of caspase-3 and cleavage of PARP, as well as the increase of Hoechst-positive stained cells and Annexin V-positive cells. Further studies find that Bax-mediated permeabilization of mitochondrial membrane is critical for cell apoptosis, as well as the cytosolic leakage of mtDNA in UVB-treated cells, which results in cGAS-STING activation, and these processes are negatively-regulated by PINK1/parkin-mediated mitophagy. This study reveals the involvement of dysfunctional mitochondria due to impaired mitophagy in the damaging effect of UVB irradiation on HaCaT cells. Restoring the mitophagy has the potential to be developed as a new strategy to protect skin from UVB damages. [Display omitted] • UVB decreases mitophagy and accumulates dysfunctional mitochondria in HaCaT cells. • UVB reduces PINK1/parkin expression that is involved in mitophagy of damaged mitochondria. • Mitophagy arrest caused by UVB leads to the activation of cGAS-STING/apoptosis pathway. • Mitophagy arrest caused by UVB increases mitochondrial membrane permeability. • Mitophagy arrest caused by UVB results in the mtDNA leakage into cytosol. [ABSTRACT FROM AUTHOR]

We previously reported that silibinin induced a loss of cell viability in breast cancer (MCF-7) cells by ERα down-regulation. But whether this cytotoxicity depends on another estrogen receptor, ERβ, has yet to be elucidated. Therefore, we sought to explore the effects of ERβ modulation on cell viability by using an ERβ-selective agonist (Diarylprepionitrile, DPN) and an antagonist (PHTPP). Our data demonstrated that ERβ served as a growth suppressor in MCF-7 cells, and the incubation of silibinin, elevated ERβ expression, resulting in the tumor growth inhibition. The cytotoxic effect of silibinin was diminished by PHTPP and enhanced by DPN. Silencing of ERβ by siRNA confirmed these results. Apoptotic cascades, including the sequential activation of caspase-9 and -6, and finally the cleavage of caspase substrates, PARP and ICAD, caused by treatment with silibinin, were all repressed by PHTPP pre-treatment but exacerbated by DPN. Unlike ERα, ERβ did not involve autophagic process in the regulation, since neither autophagic inhibitor (3-MA) nor the inducer (rapamycin) affected the cell survival rates regardless ERβ activity. Taken together, silibinin induced apoptosis through mitochondrial pathway by up-regulating ERβ pathways in MCF-7 cells without the involvement of autophagy. [ABSTRACT FROM AUTHOR]

Collagen I is a major component of extracellular matrix in human skin, and is also widely used in a variety of skin-care products. In this study, we investigated the modulatory roles of collagen I on human immortalized keratinocytes HaCaT, especially when cells were irradiated with UVB. Interestingly, the cells grown on plates coated by molecular collagen I, but not fibrillar collagen I, acquired certain resistance against UVB damages, as shown by increased survival and reduced apoptosis. The accumulation of dysfunctional mitochondria in UVB-treated cells was attenuated by molecular collagen I-coating. Interestingly, molecular collagen I rescued the loss of mitochondrial biogenesis in cells treated with UVB. Loss of PINK1/parkin-mediated mitophagy was dominant for the accumulation of dysfunctional mitochondria after UVB irradiation. Of note, cells cultured on molecular collagen I-precoated plates exhibited reserved mitophagy after UVB irradiation, as reflected by the enhanced protein level of PINK1/parkin, increased mitochondrial ubiquitin and the co-localization of lysosomes and mitochondria. Moreover, in UVB-treated cells, inhibiting mitophagy by Cyclosporin A, or by silencing PINK1 or parkin, disturbed the resolution of mitochondrial stress and reduced the protective effect of molecular collagen I, indicating that mitophagy is pivotal for the protection of collagen I against UVB damage in keratinocytes HaCaT. Collectively, this study reveals an unexpected protective role of collagen I, which facilitates mitophagy to rescue cells under UVB irradiation, providing a new direction for clinical application of collagen products. [Display omitted] • Precoating culture plates with collagen I alleviates UVB-induced HaCaT cell apoptosis. • Collagen I inhibits the accumulation of damaged mitochondria in UVB-treated cells. • Arrest of mitophagy accelerates UVB damage by accumulating damaged mitochondria. • UVB protection caused by collagen I depends on rescuing mitophagy. [ABSTRACT FROM AUTHOR]

In this work, an environmentally friendly strategy was used to synthesize gold nanoparticles (Au NPs) using Olea europaea (olive) fruit. Transmission electron microscopy (TEM), UV–Vis spectroscopy, X-ray diffraction (XRD) and energy-dispersive X-ray (EDX) were used to characterize the physicochemical properties of the synthesized NPs. An Au NPs modified glassy carbon electrode was used to investigate the direct electrochemical oxidation of hydrazine. The suggested hydrazine sensor has good performance, such as a wide linear range (2.5–275 μM), low limit of detection (0.09 μM), notable selectivity and excellent reproducibility (RSD = 2.2%). The in-vitro cytotoxicity of three human cancer cell lines (KATOIII, NCI-N87, and SNU-16) was also explored with various concentrations of Au NPs prepared from olive fruit extract. Bio-synthesized Au NPs were found to have cytotoxic properties against gastric cancer in humans based on MTT assay protocol. The obtained results show that green synthesized Au NPs can be successfully employed in electrochemical sensing and cancer treatment applications. [Display omitted] • Au NPs were fabricated with a green approach using the Olea europaea (olive) fruit extract. • High anticancer activity was obtained against KATOIII, NCI-N87, and SNU-16 gastric cancer cells at different concentrations of Au NPs. • The biogenic Au NPs were successfully used to fabricate an effective hydrazine electrochemical sensor. [ABSTRACT FROM AUTHOR]

[Display omitted] • 53 new SSU, ITS1-5.8S rDNA-ITS2, and LSU rDNA sequences of spirotrich ciliates. • Novistrombidium asserts an ancestral ciliary pattern in Oligotrichia. • Division of subgenera Novistrombidium and Parallelostrombidium is fully supported. • Cyrtostrombidiidae, Pelagostrombidiidae and Tontoniidae evolved from Strombidiidae. Marine planktonic ciliates are largely oligotrichs and choreotrichs, which are two subclasses of the class Spirotrichea. The current phylogenetic assignments of oligotrichs and choreotrichs are inconsistent with previous results based on morphological features, probably hindered by the limited information from a single gene locus. Here we provide 53 new sequences from small subunit ribosomal RNA (SSU rDNA), ITS1-5.8S rDNA-ITS2, and large subunit ribosomal RNA (LSU rDNA) gene loci in 25 oligotrich and choreotrich species. We also predict RNA secondary structures for the ITS2 regions in 55 species, 48 species of which are reported for the first time. Based on these novel data, we make a more comprehensive phylogenetic reconstruction, revealing consistency between morphological taxonomy and an updated phylogenetic system for oligotrichs and choreotrichs. With the addition of data from ciliature patterns and genes, the phylogenetic analysis of the subclass Oligotrichia suggests three evolutionary trajectories, among which: 1) Novistrombidium asserts an ancestral ciliary pattern in Oligotrichia; 2) the subgenera division of Novistrombidium and Parallelostrombidium are fully supported; 3) the three families (Tontoniidae, Pelagostrombidiidae and Cyrtostrombidiidae) all evolved from the most diverse family Strombidiidae, which explains why strombidiids consistently form polyphyletic clades. In the subclass Choreotrichia, Strombidinopsis likely possesses an ancestral position to other choreotrichs, and both phylogenetic analysis and RNA secondary structure prediction support the hypothesis that tintinnids may have evolved from Strombidinopsis. The results presented here offer an updated hypothesis for the evolutionary history of oligotrichs and choreotrichs based on new evidence obtained by expanding sampling of molecular information across multiple gene loci. [ABSTRACT FROM AUTHOR]

We reported previously that higher doses (150–250 μM) of silibinin enhanced fission and inhibited fusion of mitochondria, accompanying apoptosis of double-positive breast cancer cell line MCF-7 cells and triple-negative breast cancer cell line MDA-MB-231 cells. We report here three important questions yet unclarified in the previous study; 1) Whether enhanced fission of mitochondria by the treatment of silibinin leads to mitophagy, 2) Whether mitophagy positively contributes to apoptosis and 3) Whether estrogen receptor-positive (ER+) MCF-7 cells and estrogen receptor-negative (ER−) MDA-MB-231 cells are affected in a different way by silibinin treatment, since silibinin often works through ERs signaling pathway. Mitophagy driven by Pink1/Parkin signaling, plays an important role in eliminating damaged mitochondria. Indeed, increased expression of Pink1 and the recruitment of Parkin and LC3-II to mitochondria by the treatment with silibinin account for silibinin induction of mitophagy. In this study, the effects of mitochondrial division inhibitor 1 (mdivi-1) and small interfering RNA targeting dynamin-related protein 1 (DRP1) were examined to reveal the effect of mitochondrial fission on mitophagy. As expected, mdivi-1 or siRNA targeting DRP1 reversed silibinin-induced mitochondrial fission due to down-regulation in the expression of DRP1. Inhibition of mitochondrial fission by mdivi-1 prevented induction of mitophagy as well as autophagy in both MCF-7 and MDA-MB-231 cells, indicating that silibinin-induced mitochondrial fission leads to mitophagy. Inhibition of mitochondrial fission efficiently prevented silibinin-induced apoptosis in MCF-7 and MDA-MB-231 cells in our previous work, and the second point of the present study, inhibition of mitophagy by Pink1 or Parkin knockdown increased silibinin-induced apoptosis of these cells, respectively, suggesting that the mitophagy induced by silibinin treatment serves as a cytoprotective effect, resulting in reduction of apoptosis of cancer cells in both cells. In the third point, we studied whether estrogen receptors (ERs) played a role in silibinin-induced mitophagy and apoptosis in MCF-7 and MDA-MB-231 cells. ERα and ERβ are not involved in silibinin-induced mitophagic process in MCF-7 and MDA-MB-231 cells. These findings demonstrated that silibinin induced mitochondria fission leads to mitophagy, which attenuates silibinin-induced apoptosis not through ERs-Pink1 or -Parkin pathway in MCF-7 and MDA-MB-231. [ABSTRACT FROM AUTHOR]

Ferroptosis, an iron-dependent cell death, is caused by lipid peroxidation. Noteworthily, accumulation of iron and lipid peroxidation are found in the proximity of the neuritic plaque, a hallmark of Alzheimer's disease (AD), but the relationship between ferroptosis and neuroinflammation in AD is unclear. Silibinin, extracted from the Silybum marianum , is possibly developed as an agent for AD treatment from its neuroprotective effect, but the effect of silibinin on sporadic AD that accounts for more than 95% of AD remains unclear. To determine whether silibinin alleviates the pathogenesis of sporadic AD and investigate the underlying mechanisms, STZ-treated HT22 murine hippocampal neurons and intracerebroventricular injection of streptozotocin (ICV-STZ) rats, a sporadic AD model, were used in this study. Results show that silibinin not only promotes survival of STZ-treated HT22 cells, but also ameliorates the cognitive impairment and anxiety/depression-like behavior of ICV-STZ rats. We here demonstrate that silibinin evidently inhibits the protein level of p53 as well as upregulates the protein level of cystine/glutamate antiporter SLC7A11 and ferroptosis inhibitor GPX4, but not p21, leading to the protection against STZ-induced ferroptotic damage. Immunofluorescent staining also shows that accumulation of lipid peroxidation induced by ferroptotic damage leads to increased fluorescence of 8-oxo-deoxyguanosine (8-OHDG), a maker of oxidized DNA. The oxidized DNA then leaks to the cytoplasm and upregulates the expression of the stimulator of interferon gene (STING), which triggers the production of IFN-β and other inflammatory cascades including NF-κB/TNFα and NLRP3/caspase 1/IL-1β. However, the treatment with silibinin blocks the above pathological changes. Moreover, in HT22 cells with/without STZ treatment, GPX4-knockdown increases the protein level of STING, indicating that the ferroptotic damage leads to the activation of STING signaling pathway. These results imply that silibinin exerts neuroprotective effect on an STZ-induced sporadic AD model by downregulating ferroptotic damage and thus the downstream STING-mediated neuroinflammation. [Display omitted] • Silibinin downregulates p53-mediated ferroptosis in STZ-treated HT22 murine hippocampal neurons. • Silibinin ameliorates cognitive deficit and anxiety/depression-like behaviors of ICV-STZ rats. • Silibininreduces STING-mediated neuroinflammation via down-regulating ferroptotic damage both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

In this paper, BaTiO 3 platelets are utilized for the first time to incorporate into polymer matrix for energy storage. To improve the dispersibility and compatibility of the BaTiO 3 platelets in the composites, a new type of fluoro-polymer poly{2,5-bis[(2,3,5,6-tetrafluoro-4-trifluoromethyl)oxycarbonyl]styrene} (PM7F) was designed for the first time to engineer the surface of BaTiO 3 platelets by surface-initiated reversible-addition-fragmentation chain transfer polymerization method. Each structural unit in the molecular chain of this novel modifier contained 14 fluorine atoms, resulting in effectively decreasing the surface energy of BaTiO 3 platelets. As a result, the BaTiO 3 platelets modified by PM7F were homogeneously dispersed in the polymer poly(vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) (P(VDF-TrFE-CTFE)) matrix. The permittivities of the nanocomposites were significantly improved compared with the pure polymer matrix. The energy storage density of the nanocomposites was largely enhanced by adding the BaTiO 3 platelets. The discharged energy density of the nanocomposite with 15 vol% BaTiO 3 platelets was 1.26 J/cm 3 , which was nearly double to that of pure P(VDF-TrFE-CTFE) (0.64 J/cm 3 ) at the same electric field (60 kV/mm). The findings provide an effective modifier and a new routine for high performance capacitors. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2DM) is induced by the abundance of glucose and lipids, which causes glucolipotoxicity to the pancreatic β-cells. Silibinin is a natural flavonoid possessing the regulatory activity on insulin production and therapeutic activity in diabetic mice; however, its effect on glucolipotoxicity is not fully explained. This in vitro study investigates the effects of silibinin on palmitic acid (PA) and high glucose (HG)-induced cell loss and ferroptosis of rat insulinoma INS-1 cells. In the cells treated with PA and HG, expressions of glucose transporter 4 (Glut4) and carnitine acyltransferase I (CPT1) for β-oxidation of fatty acids are reduced. Mitochondria are the metabolic organelles for glucose and fatty acids. The mitochondrial membrane potential (MMP) and ATP production were decreased, while the ROS level was elevated in the cells treated with PA and HG, indicating an induction of mitochondrial disorder. Cell loss was partially rescued by ferroptosis inhibition, suggesting an involvement of ferroptosis in the cells treated with PA and HG. More importantly, the increases in total iron, lipid ROS, MDA and COX-2, and the decrease in ferroptosis inhibitory molecules GSH, GPX4 and FSP1 appeared in the cells treated with PA and HG, confirming the occurrence of ferroptosis. Moreover, PINK1/parkin-mediated mitophagy, a vital process for selective elimination of damaged mitochondria, was blocked. Interestingly, silibinin rescued the mitochondria, restricted the ferroptosis and restored the mitophagy. By using the pharmacological stimulator and inhibitor of mitophagy, and si-RNA transfection to silence PINK1 expression, silibinin's protective effect against ferroptosis caused by PA and HG treatment was found to depend on mitophagy. Collectively, our current study reveals the new mechanisms for the protection of silibinin against the injury of INS-1 cells treated with PA and HG, elucidates the participation of ferroptosis in glucolipotoxicity, highlighting the involvement of mitophagy in defense against ferroptotic cell death. [Display omitted] • Silibinin improves the mitochondrial function in INS-1 cells treated with palmitic acid and high glucose. • Silibinin alleviates the reduction of PINK1/parkin-mediated mitophagy in INS-1 cells treated with palmitic acid and high glucose. • Silibinin attenuates ferroptosis in INS-1 cells treated with palmitic acid and high glucose. • Silibinin-induced mitophagy negatively regulates ferroptosis in INS-1 cells treated with palmitic acid and high glucose. [ABSTRACT FROM AUTHOR]

The pilot study aims to explore the efficacy and safety of baricitinib in treating refractory intestinal Behçet's disease (BD). We consecutively enrolled patients with refractory intestinal BD from October 2020 to September 2022. They were treated with baricitinib 2-4 mg daily, with background glucocorticoids and immunosuppressants. Efficacy assessment included the global gastrointestinal symptom scores, the endoscopy scores, the Disease activity index for intestinal Behçet's disease (DAIBD), and the inflammatory parameters. Side effects were recorded. The thirteen patients (six males and seven females) had a median follow-up of eleven months, 76.92% (10/13) patients achieved complete remission of global gastrointestinal symptom scores, and 66.7% (6/9) had mucosal healing on endoscopy. The DAIBD scores decreased significantly, as well as the C-reactive protein level. Baricitinib showed a glucocorticoid-sparing effect, and the safety profile is favorable. Baricitinib might be a potential choice in treating refractory intestinal BD. • Treating patients with intestinal Behçet's disease (BD) refractory to conventional therapies and (or) biologics is challenging • Baricitinib showed a favorable efficacy and safety profile in treating refractory intestinal BD. • Baricitinib had a favorable glucocorticoid-sparing effect on refractory intestinal BD. [ABSTRACT FROM AUTHOR]

Background Early life is suggested to be a critical time in determining subsequent asthma development, but the extent to which the effect of early-life exposure to ambient air pollution on childhood asthma is unclear. Objectives We investigated doctor-diagnosed asthma in preschool children due to exposure to ambient air pollution in utero and during the first year of life. Methods In total 2490 children aged 3–6 years participated in a questionnaire study regarding doctor-diagnosed asthma between September 2011 and January 2012 in China. Children’s exposure to critical air pollutants, sulfur dioxide (SO 2 ) as proxy of industrial air pollution, nitrogen dioxide (NO 2 ) as proxy of traffic pollution, and particulate matter≤10 µm in diameter (PM 10 ) as a mixture, was estimated from the concentrations measured at the ambient air quality monitoring stations by using an inverse distance weighted (IDW) method. Logistic regression analysis was employed to determine the relationship between early-life exposure and childhood asthma in terms of odds ratio (OR) and 95% confidence interval (CI). Results Association between early-life exposure to air pollutants and childhood asthma was observed. SO 2 and NO 2 had significant associations with adjusted OR (95% CI) of 1.45 (1.02–2.07) and 1.74 (1.15–2.62) in utero and 1.62 (1.01–2.60) and 1.90 (1.20–3.00) during the first year for per 50 µg/m 3 and 15 µg/m 3 increase respectively. Exposure to the combined high level of SO 2 and NO 2 in China significantly elevated the asthmatic risk with adjusted OR (95% CI) of 1.76 (1.18–2.64) in utero and 1.85 (1.22–2.79) during the first year compared to the low level exposure. The associations were higher for males and the younger children aged 3–4 than females and the older children aged 5–6. Conclusions Early-life exposure to ambient air pollution is associated with childhood asthma during which the level and source of air pollution play important roles. The high level and nature of combined industrial and traffic air pollution in China may contribute to the recent rapid increase of childhood asthma. [ABSTRACT FROM AUTHOR]

Owing to the mounting evidence of serum lipid changes in atherosclerosis, there has been increasing interest in developing new methods for analyzing atherogenic lipoprotein profiles. The separation of lipoprotein and lipoprotein subclasses has been demonstrated using a microchip capillary electrophoresis (CE) system [Chromatographia 74 (2011) 799–805]. In contrast to this previous study, the current report demonstrates that sdLDL peak efficiencies can be improved dramatically by adding gold nanoparticles (AuNPs) to the sample. Moreover, NBD C 6 -ceramide was identified as a satisfactory dye for specific labeling and quantitation of individual serum lipoproteins. The accuracy of the method was evaluated by comparison with ultracentrifuge separated small, dense, low-density lipoprotein (sdLDL). A high correlation was observed between these two methods for sdLDL cholesterol. Lipid levels were investigated between atherosclerotic patients and healthy controls. The variation of serum atherogenic lipoprotein profiles for atherosclerotic patients pre- and post-treatment was assessed by microchip CE. This method has potential for the rapid and sensitive detection of different lipoprotein classes as well as their subclasses and, therefore, is suitable for routine clinical applications. Microchip-based atherogenic lipoprotein profile assays will greatly improve the analysis of risk factors in atherosclerosis and will provide useful information for monitoring the effect of therapies on atherosclerotic disease. [ABSTRACT FROM AUTHOR]

The purine utilization pathway has been thoroughly characterized in Aspergillus nidulans. We establish here the subcellular distribution of seven key intracellular enzymes, xanthine dehydrogenase (HxA), urate oxidase (UaZ), 5-hydroxy-isourate hydrolase (UaX), 2-oxo-4-hydroxy-4-carboxy ureido imidazoline decarboxylase (UaW), allantoinase (AIX), allantoicase (AaX), ureidoglycolate lyase (UgIA), and the fungal-specific α-ketoglutarate Fe(II)-dependent dioxygenase (XanA). HxA, AIX, AaX, UaW and XanA are cytosolic, while UaZ, UaX and UglA are peroxisomal. Peroxisomal localization was confirmed by using appropriate pex mutants. The pathway is largely, but not completely conserved in the Eurotiomycetes, noticeably in some species AaX is substituted by an alternative enzyme of probable bacterial origin. UaZ and the urate--xanthine UapA and UapC transporters, are also localized in specific cells of the conidiophore. We show that metabolic accumulation of uric acid occurring in uaZ null mutations is associated with an increased frequency of appearance of morphologically distinct colony sectors, diminished conidiospore production, UV resistance and an altered response to oxidation stress, which may provide a rationale for the conidiophore-specific localization. The pathway-specific transcription factor UaY is localized in both the cytoplasm and nuclei under non-inducing conditions, but it rapidly accumulates exclusively to the nuclei upon induction by uric acid. [ABSTRACT FROM AUTHOR]

Highlights: [•] Germline potential could be spontaneously activated in human hepatoblastoma cells. [•] Germ cell-like cells likely play important roles in the malignant traits of Huh6 cells. [•] Understanding why hepatoblastomas possess a strong germ cell/embryonic nature. [Copyright &y& Elsevier]

Abstract: Oxidative damage to DNA induced by benzene is an important mechanism of its genotoxicity, which leads to chronic benzene poisoning (CBP). Therefore, genetic variation in DNA repair genes may contribute to susceptibility to CBP in the exposed population. We hypothesized that single nucleotide polymorphisms (SNPs) in hMTH1, hOGG1 and hMYH genes are associated with risk of CBP. We genotyped SNPs at codon 83 of hMTH1, codon 326 of hOGG1, and codon 324 of hMYH in 152 CBP patients and 152 healthy workers occupationally exposed to benzene without poisoning manifestations. The genotypes were determined by polymerase chain reaction-restrained fragment length polymorphism (PCR-RFLP) technique. There were 2.51-fold [adjusted odds ratio (ORadj), 2.51; 95% CI, 1.14–5.49; P =0.02] and 2.49-fold (ORadj, 2.49; 95% CI: 1.52–4.07; P <0.01) increased risk of CBP for individuals carrying genotypes of hMTH1 83Val/Met+Met/Met and hOGG1 326Cys/Cys, respectively. Compared with individuals carrying genotypes of hOGG1 326Cys/Cys and hMYH 324His/His at the same time, there was a 0.33-fold (ORadj, 0.33; 95% CI: 0.15–0.72; P <0.05) decreased risk of CBP for those with genotypes of hOGG1 326Ser/Cys+Ser/Ser and hMYH 324His/Gln+Gln/Gln. In the smoking group, there was a 0.15-fold (ORadj, 0.15; 95% CI, 0.03–0.68; P =0.01) decreased risk of CBP for subjects carrying genotypes of hMYH 324His/Gln+Gln/Gln compared with those of genotype of hMYH 324His/His. Therefore, our results suggested that polymorphisms at codons 83 of hMTH1 and codon 326 of hOGG1 might contribute to CBP in a Chinese occupational population. [Copyright &y& Elsevier]