The production of clean and renewable hydrogen through water splitting using photocatalysts has received much attention due to the increasing global energy crises. In this study, a high efficiency of ...the photocatalytic H2 production was achieved using graphene nanosheets decorated with CdS clusters as visible-light-driven photocatalysts. The materials were prepared by a solvothermal method in which graphene oxide (GO) served as the support and cadmium acetate (Cd(Ac)2) as the CdS precursor. These nanosized composites reach a high H2-production rate of 1.12 mmol h–1 (about 4.87 times higher than that of pure CdS nanoparticles) at graphene content of 1.0 wt % and Pt 0.5 wt % under visible-light irradiation and an apparent quantum efficiency (QE) of 22.5% at wavelength of 420 nm. This high photocatalytic H2-production activity is attributed predominantly to the presence of graphene, which serves as an electron collector and transporter to efficiently lengthen the lifetime of the photogenerated charge carriers from CdS nanoparticles. This work highlights the potential application of graphene-based materials in the field of energy conversion.
Most patients with breast cancer in advanced stages of the disease suffer from bone metastases which lead to fractures and nerve compression syndromes. microRNA dysregulation is an important event in ...the metastases of breast cancer to bone. microRNA-124 (miR-124) has been proved to inhibit cancer progression, whereas its effect on bone metastases of breast cancer has not been reported. Therefore, this study aimed to investigate the role and underlying mechanism of miR-124 in bone metastases of breast cancer.
In situ hybridization (ISH) was used to detect the expression of miR-124 in breast cancer tissues and bone metastatic tissues. Ventricle injection model was constructed to explore the effect of miR-124 on bone metastasis in vivo. The function of cancer cell derived miR-124 in the differentiation of osteoclast progenitor cells was verified in vitro. Dual-luciferase reporter assay was conducted to confirm Interleukin-11 (IL-11) as a miR-124 target. The involvement of miR-124/IL-11 in the prognosis of breast cancer patients with bone metastasis was determined by Kaplan-Meier analysis.
Herein, we found that miR-124 was significantly reduced in metastatic bone tissues from breast cancers. Down-regulation of miR-124 was associated with aggressive clinical characteristics and shorter bone metastasis-free survival and overall survival. Restoration of miR-124 suppressed, while inhibition of miR-124 promoted the bone metastasis of breast cancer cells in vivo. At the cellular level, gain of function and loss-of function assays indicated that cancer cell-derived miR-124 inhibited the survival and differentiation of osteoclast progenitor cells. At the molecular level, we demonstrated that IL-11 partially mediated osteoclastogenesis suppression by miR-124 using in vitro and in vivo assays. Furthermore, IL-11 levels were inversely correlated with miR-124, and up-regulation IL-11 in bone metastases was associated with a poor prognosis.
Thus, the identification of a dysregulated miR-124/IL-11 axis helps elucidate mechanisms of breast cancer metastases to bone, uncovers new prognostic markers, and facilitates the development of novel therapeutic targets to treat and even prevent bone metastases of breast cancer.
Ferroptosis is a form of iron-dependent regulated cell death. Evidence of its existence and the effects of its inhibitors on subarachnoid hemorrhage (SAH) is still lacking. In the present study, we ...found that liproxstatin-1 protected HT22 cells against hemin-induced injury by protecting mitochondrial functions and ameliorating lipid peroxidation. In
in vivo
experiments, we demonstrated the presence of characteristic shrunken mitochondria in ipsilateral cortical neurons after SAH. Moreover, liproxstatin-1 attenuated the neurological deficits and brain edema, reduced neuronal cell death, and restored the redox equilibrium after SAH. The inhibition of ferroptosis by liproxstatin-1 was associated with the preservation of glutathione peroxidase 4 and the downregulation of acyl-CoA synthetase long-chain family member 4 as well as cyclooxygenase 2. In addition, liproxstatin-1 decreased the activation of microglia and the release of IL-6, IL-1β, and TNF-α. These data enhance our understanding of cell death after SAH and shed light on future preclinical studies.
Aberrant modulation of mitochondrial dynamic network, which shifts the balance of fusion and fission towards fission, is involved in brain damage of various neurodegenerative diseases including ...Parkinson's disease, Huntington's disease and Alzheimer's disease. A recent research has shown that the inhibition of mitochondrial fission alleviates early brain injury after experimental subarachnoid hemorrhage, however, the underlying molecular mechanisms have remained to be elucidated. This study was undertaken to characterize the effects of the inhibition of dynamin-related protein-1 (Drp1, a dominator of mitochondrial fission) on blood-brain barrier (BBB) disruption and neuronal apoptosis following SAH and the potential mechanisms. The endovascular perforation model of SAH was performed in adult male Sprague Dawley rats. The results indicated Mdivi-1(a selective Drp1 inhibitor) reversed the morphologic changes of mitochondria and Drp1 translocation, reduced ROS levels, ameliorated the BBB disruption and brain edema remarkably, decreased the expression of MMP-9 and prevented degradation of tight junction proteins—occludin, claudin-5 and ZO-1. Mdivi-1 administration also inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB), leading to decreased expressions of TNF-ɑ, IL-6 and IL-1ß. Moreover, Mdivi-1 treatment attenuated neuronal cell death and improved neurological outcome. To investigate the underlying mechanisms further, we determined that Mdivi-1 reduced p-PERK, p-eIF2α, CHOP, cleaved caspase-3 and Bax expression as well as increased Bcl-2 expression. Rotenone (a selective inhibitor of mitochondrial complexes I) abolished both the anti-BBB disruption and anti-apoptosis effects of Mdivi-1. In conclusion, these data implied that excessive mitochondrial fission might inhibit mitochondrial complex I to become a cause of oxidative stress in SAH, and the inhibition of Drp1 by Mdivi-1 attenuated early brain injury after SAH probably via the suppression of inflammation-related blood–brain barrier disruption and endoplasmic reticulum stress-based apoptosis.
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•SAH could result in mitochondrial morphological changes, Drp1 translocation onto mitochondria and ROS increase.•Mdivi-1 may induce the expression of mitochondrial complex I to reduce SAH-induced oxidative stress.•Mdivi-1 may inhibit oxidative stress-induced NF-κB-dependent BBB disruption to attenuate brain edema in SAH.•Mdivi-1 protects neuron against apoptosis probably through the inhibition of the PERK/ eIF2α/ CHOP pathway.
Non‐alcoholic fatty liver disease (NAFLD) has become a worldwide epidemic over the last decade. Remarkable progress has been made in understanding the pathogenesis of NAFLD and, subsequently, in ...developing medications to treat this disease. Although the mechanisms of NAFLD are complex and multifactorial, accumulating and emerging evidence indicates that mitochondria play a critical role in the pathogenesis and progression of NAFLD. Pharmacologic therapies acting on mitochondria may therefore pave the way to novel strategies for the prevention and protection against NAFLD. This review focuses on new insights into the role of hepatic mitochondrial dysfunction in NAFLD, and summarizes recent studies on mitochondria‐centric therapies for NAFLD utilizing new medications or repurposing of currently available drugs. Although some studies presented may feature controversial results or are still in lack of clinical verification, it is undoubted that medications that may spare the mitochondria from multiple levels of damage are highly promising, and have begun to be used with some degree of success.
Mitochondria play a critical role in pathogenesis of non‐alcoholic fatty liver disease (NAFLD). Mitochondrial dysfunction promotes steatosis, fatty acid peroxidation and reactive oxygen species (ROS) overproduction, which finally activate inflammation. NAFLD therapeutics from a mitochondria‐centric perspective may be promising. These mitochondria‐centric therapies include antioxidants targeting ROS, agonists or inhibitors targeting key mitochondrial enzymes, and regulators involved in signaling pathways.
Bacterial infection is one of the most serious public health problems, being harmful to human health and expensive. Nowadays, the misuse and overuse of antibiotics have led to the emergence of drug ...resistance. Therefore, it is an urgent need to develop new antimicrobial agents to address the current situation. In this study, four 1,2,4-triazole ruthenium polypyridine complexes Ru(bpy)
(TPIP)(PF
)
(Ru1), Ru(dmb)
(TPIP)(PF
)
(Ru2), Ru(dtb)
(TPIP)(PF
)
(Ru3) and Ru(dmob)
(TPIP)(PF
)
(Ru4) (bpy = 2,2'-bipyridine, dmb = 4,4'-dimethyl-2,2'-bipyridine, dtb = 4,4'-di-
-butyl-2,2'-bipyridine, dmob = 4,4'-dimethoxy-2,2'-bipyridine and TPIP = 2-(4-(1
-1,2,4-triazol-1-yl)phenyl)-1
-imidazo4,5-
1,10phenanthroline) were synthesized and evaluated for antibacterial activity. Results showed that the minimum inhibitory concentration (MIC) value of Ru3 against
(
) was only 0.78 μg mL
, showing the best antimicrobial activity
. Besides, Ru3 showed low hemolytic activity and good biocompatibility. Due to its ability to damage the cell membrane of
bacteria, Ru3 was able to kill bacteria in a short time. Importantly, by inhibiting bacterial toxins and the formation of biofilm, Ru3 was not susceptible to the development of drug resistance. Moreover, Ru3 revealed excellent therapeutic effects
and showed no irritation to the skin of mice. In conclusion, the four obtained 1,2,4-triazole ruthenium polypyridine complexes show strong antibacterial activity and satisfactory biocompatibility with excellent potential for antibacterial treatment, and provide a new solution for the current antibacterial crisis.
ABSTRACT
Innovations in genomics have enabled the development of low‐cost, high‐resolution, single nucleotide polymorphism (SNP) genotyping arrays that accelerate breeding progress and support basic ...research in crop science. Here, we developed and validated the SoySNP618K array (618,888 SNPs) for the important crop soybean. The SNPs were selected from whole‐genome resequencing data containing 2,214 diverse soybean accessions; 29.34% of the SNPs mapped to genic regions representing 86.85% of the 56,044 annotated high‐confidence genes. Identity‐by‐state analyses of 318 soybeans revealed 17 redundant accessions, highlighting the potential of the SoySNP618K array in supporting gene bank management. The patterns of population stratification and genomic regions enriched through domestication were highly consistent with previous findings based on resequencing data, suggesting that the ascertainment bias in the SoySNP618K array was largely compensated for. Genome‐wide association mapping in combination with reported quantitative trait loci enabled fine‐mapping of genes known to influence flowering time, E2 and GmPRR3b, and of a new candidate gene, GmVIP5. Moreover, genomic prediction of flowering and maturity time in 502 recombinant inbred lines was highly accurate (>0.65). Thus, the SoySNP618K array is a valuable genomic tool that can be used to address many questions in applied breeding, germplasm management, and basic crop research.
To accelerate breeding progress and support basic research in soybean, the customized SoySNP618K array contains 618,888 SNPs selected from > 2,000 diverse, re‐sequenced soybean genomes. SoySNP618K is a valuable genomic tool to address questions in applied breeding, germplasm management, and basic research.
Abstract
BACKGROUND:
Blood-brain barrier (BBB) disruption and neural apoptosis are thought to promote early brain injury (EBI) after subarachnoid hemorrhage (SAH). Previous studies have demonstrated ...that valproic acid (VPA) decreased brain injury in a prechiasmatic injection model of SAH in mice. It should be noted that the beneficial effects of VPA and the underlying mechanisms have not been fully elucidated.
OBJECTIVE:
To characterize the effects of VPA on BBB disruption and neural apoptosis and to determine mechanisms involved in EBI after SAH.
METHODS:
An endovascular perforation model was used to induce SAH in rats. VPA (300 mg/kg) was promptly administered after SAH induction, and the same dose was given 12 hours later. Quercetin (100 mg/kg), an inhibitor of heat shock protein 70 (HSP70), was injected into the peritoneum 2 hours before SAH induction. Mortality, SAH grades, neurological function, Evans Blue extravasation, brain edema, transmission electron microscopy, Western blot, double fluorescence labeling, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling staining also were used.
RESULTS:
VPA treatment decreased BBB disruption and brain edema, attenuated neural apoptosis, and improved neurobehavioral functions in EBI after SAH. Double fluorescence labeling indicated that matrix metallopeptidase 9 (MMP-9) was located predominately in neurons and endothelial cells. VPA upregulated the expression of HSP70, effectively decreased the expression and activity of MMP-9, and reduced claudin-5 and occludin degradation. Meanwhile, VPA also upregulated the expression of phosphorylated Akt and bcl-2. Both the anti-BBB disruption and antiapoptotic effects of VPA were abolished by quercetin.
CONCLUSION:
VPA prevented BBB disruption and alleviated neural apoptosis after SAH. The action of VPA appeared to be mediated though the HSP70/MMPs and HSP70/Akt pathways.
Bisphenol A (BPA) and 4‐nonylphenol (NP) are well‐known endocrine‐disrupting chemicals (EDCs) that have been proven to affect Leydig cell (LC) functions and testosterone production, but whether BPA ...and NP have multi‐ and transgenerational biochemical effects on Leydig cells (LCs) is unknown. Fourier transform infrared (FTIR) spectroscopy is a powerful analytical technique that enables label‐free and non‐destructive analysis of the tissue specimen. Herein we employed FTIR coupled with chemometrics analysis to identify biomolecular changes in testicular interstitial (Leydig) cells of rats after chronic exposure to low doses of BPA and NP. Cluster segregations between exposed and control groups were observed based on the fingerprint region of 1800–900 cm−1 in all generations. The main biochemical alterations for segregation were amide I, amide II and nucleic acids. BPA and NP single and co‐exposure induced significant differences in the ratio of amide I to amide II compared to the corresponding control group in all generations. BPA exposure resulted in remarkable changes of cellular gene transcription and DNA oxidative damage across all generations. Direct exposure to BPA, NP, and BPA&NP of F0 and F1 generations could significantly decrease lipid accumulation in LCs in the F2 and F3 generations. The overall findings revealed that single or co‐exposure to BPA and NP at environmental concentrations affects the biochemical structures and properties of LCs.
With the development of medicine, our research on Alzheimer's disease (AD) has been further deepened, but the mechanism of its occurrence and development has not been fully revealed, and there is ...currently no effective treatment method. Several studies have shown that apolipoprotein AI (ApoA-I) can affect the occurrence and development of Alzheimer's disease by binding to amyloid β (Aβ). However, the association between circulating levels of ApoA-I and AD remains controversial. We conducted a meta-analysis of 18 studies published between 1992 and 2017 to determine whether the ApoA-I levels in the blood and cerebrospinal fluid (CSF) are abnormal in AD. Literatures were searched in PubMed, EMBASE and Web of Science databases without language limitations. A pooled subject sample including 1,077 AD patients and 1,271 healthy controls (HCs) was available to assess circulating ApoA-I levels; 747 AD patients and 680 HCs were included for ApoA-I levels in serum; 246 AD patients and 456 HCs were included for ApoA-I levels in plasma; 201 AD patients and 447 HCs were included for ApoA-I levels in CSF. It was found that serum and plasma levels of ApoA-I were significantly reduced in AD patients compared with HCs {standardized mean difference (SMD) = -1.16; 95% confidence interval (CI) (-1.72, -0.59);
= 0.000 and SMD = -1.13; 95% CI (-2.05, -0.21);
= 0.016}. Patients with AD showed a tendency toward higher CSF ApoA-I levels compared with HCs, although this difference was non-significant SMD = 0.20; 95% CI (-0.16, 0.56);
= 0.273. In addition, when we analyzed the ApoA-I levels of serum and plasma together, the circulating ApoA-I levels in AD patients was significantly lower SMD = -1.15; 95% CI (-1.63, -0.66);
= 0.000. These results indicate that ApoA-I deficiency may be a risk factor of AD, and ApoA-I has the potential to serve as a biomarker for AD and provide experimental evidence for diagnosis of AD.
PROSPERO, identifier: 325961.
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