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•MoS2/PVP hybrid nanocomposite was prepared by liquid-phase exfoliation.•Inkjet-printed MoS2/PVP sensor exhibited high sensitivity, ultrafast response/recovery behavior and good ...reproducibility towards humidity gas.•The enhanced humidity sensing performance was due to the synergistic effect between MoS2 and PVP.
An inkjet-printed humidity sensor based on molybdenum disulfide (MoS2) mixed with polyvinyl pyrrolidone (PVP) has been demonstrated in this work. MoS2/PVP ink was produced via a liquid-phase ultrasonic exfoliation, and then deposited on predifined interdigitated copper electrodes by inkjet printing to fabricate humidity sensors. The structure, composition, and morphology characterizations revealed that the MoS2/PVP hybrid nanocomposite was doposited on copper electrode homogeneously. Hydrophilic property of MoS2/PVP film was identified by contact angle measurement. The humidity sensing properties of MoS2/PVP film revealed a high sensitivity, ultrafast response/recovery behavior and good reproducibility. Moreover, the MoS2/PVP humidity sensor could be used to monitor the human respiratory rate. The enhanced humidity sensing performance was due to the synergistic effect between MoS2 and PVP. This work opens new opportunities for the large-scale fabrication of flexible MoS2-based humidity sensor towards various applications.
The COP9 signalosome (CSN) is a multiprotein complex that plays a critical role in diverse cellular and developmental processes in various eukaryotic organisms. Despite of its significance, current ...understanding of the biological functions and regulatory mechanisms of the CSN complex is still very limited. To unravel these molecular mechanisms, we have performed a comprehensive proteomic analysis of the human CSN complex using a new purification method and quantitative mass spectrometry. Purification of the human CSN complex from a stable 293 cell line expressing N-terminal HBTH-tagged CSN5 subunit was achieved by high-affinity streptavidin binding with TEV cleavage elution. Mass spectrometric analysis of the purified CSN complex has revealed the identity of its composition as well as N-terminal modification and phosphorylation of the CSN subunits. N-terminal modifications were determined for seven subunits, six of which have not been reported previously, and six novel phosphorylation sites were also identified. Additionally, we have applied the newly developed MAP-SILAC and PAM-SILAC methods to decipher the dynamics of the human CSN interacting proteins. A total of 52 putative human CSN interacting proteins were identified, most of which are reported for the first time. In comparison to PAM-SILAC results, 20 proteins were classified as stable interactors, whereas 20 proteins were identified as dynamic ones. This work presents the first comprehensive characterization of the human CSN complex by mass spectrometry-based proteomic approach, providing valuable information for further understanding of CSN complex structure and biological functions.
Euchromatic histone-lysine N-methyltransferase (G9A), the primary histone methyltransferase for histone H3 Lys
, has been identified to be upregulated in numerous types of cancer. The aim of the ...present study was to analyze the clinical significance of G9A, and preliminarily explore its function in hepatocellular carcinoma (HCC). An increased expression level of G9A was demonstrated in the HCC samples and also in 5 publically available datasets. By analyzing GSE14520, it was revealed that its expression level was significantly associated with serum α-fetoprotein level of patients with HCC, and may serve as a potential prognostic indicator for patients with multinodular HCC. Bioinformatics tools were utilized to predict the potential function of G9A, and the results indicated that G9A may modulate gene sets involved in RNA processing and DNA replication. G9A inhibition may suppress cell proliferation by arresting cells in G1 phase and increasing the expression level of microtubule-associated protein light chain 3β (MAP1LC3B) in Huh7 and HepG2 cells. In addition, an inverse association between the expression of G9A and LC3B was demonstrated in HCC tumor samples in the publically available GSE14520 dataset, which indicated that G9A may also have the potential to regulate MAP1LC3B expression in HCC tumor tissues. The results of the present study led to hypothesis that the G9A expression level may be of assistance in diagnosing HCC, and be a potential therapeutic target for HCC. The results provided novel evidence for additional understanding of the crucial role of G9A in tumorigenesis.
Mutations in the gene encoding Ca
-independent phospholipase A
group 6 (PLA2G6) cause the recessive familial type 14 of Parkinson's disease (PARK14). Mitochondrial dysfunction is involved in the ...pathogenesis of Parkinson's disease (PD). PLA2G6 is believed to be required for maintaining mitochondrial function. In the present study, rotenone-induced cellular model of PD was used to investigate possible molecular pathogenic mechanism of PARK14 mutant PLA2G6-induced PD. Overexpression of wild-type (WT) PLA2G6 ameliorated rotenone-induced apoptotic death of SH-SY5Y dopaminergic cells. PARK14 mutant (D331Y), (G517C), (T572I), (R632W), (N659S) or (R741Q) PLA2G6 failed to prevent rotenone-induced activation of mitochondrial apoptotic pathway and exert a neuroprotective effect. WT PLA2G6, but not PARK14 mutant PLA2G6, prevented rotenone-induced mitophagy impairment. In contrast to WT PLA2G6, PARK14 mutant PLA2G6 was ineffective in attenuating rotenone-induced decrease in mitochondrial membrane potential and increase in the level of mitochondrial superoxide. WT PLA2G6, but not PARK14 PLA2G6 mutants, restored enzyme activity of mitochondrial complex I and cellular ATP content in rotenone-treated SH-SY5Y dopaminergic cells. In contrast to WT PLA2G6, PARK14 mutant PLA2G6 failed to prevent rotenone-induced mitochondrial lipid peroxidation and cytochrome c release. These results suggest that PARK14 PLA2G6 mutants lose their ability to maintain mitochondrial function and are defective inpreventing mitochondrial dysfunction, ROS production and activation of mitochondrial apoptotic pathway in rotenone-induced cellular model of PD.
It is imperative to develop and implement newer, more effective strategies to address refractory diabetic wounds. As of now, there is currently no optimal solution for these wounds. Hypoxic human ...umbilical vein endothelial cells (HUVECs)-derived exosomes have been postulated to promote diabetic wound healing, however, its effect and molecular mechanism need further study. In this study, we aimed to investigate whether hypoxic exosomes enhance wound healing in diabetics. Based on our high-throughput sequencing, differentially expressed lncRNAs (including 64 upregulated lncRNAs and 94 downregulated lncRNAs) were found in hypoxic exosomes compared to normoxic exosomes. Interestingly, lncHAR1B was one of the prominently upregulated lncRNAs in hypoxic exosomes, showing a notable correlation with diabetic wound healing. More specifically, hypoxic exosomes were transmitted to surrounding cells, which resulted in a significant increase in lncHAR1B level, thereby relieving the dysfunction of endothelial cells and promoting the switch from M1 to M2 macrophages under high glucose conditions. Mechanistically, lncHAR1B directly interacted with the transcription factor basic helix-loop-helix family member e23 (BHLHE23), which subsequently led to its binding to the KLF transcription factor 4 (KLF4) and promoted KLF4 expression. In our in vivo experiments, the use of hypoxic exosomes-loaded HGM-QCS hydrogels (Gel-H-Exos) resulted in rapid wound healing compared to that of normoxic exosomes-loaded HGM-QCS hydrogels (Gel-N-Exos) and diabetic groups. Consequently, our study provides potentially novel therapeutic approaches aimed at accelerating wound healing and developing a practical exosomes delivery platform.
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•The impact and underlying molecular mechanisms of hypoxic exosomes were extensively studied.•Hypoxic exosomes mitigated the dysfunctions of HUVECs during high glucose via the lncHAR1B/BHLHE23/KLF4 axis in vitro.•Gel-H-Exos resulted in more M2 macrophage infiltration and neovascularization as a result of wound healing.
To conduct a systematic review and Meta-analysis to examine the association between uveitis and psoriatic disease, and to evaluate whether one condition predisposes individuals to the other.
We ...performed a comprehensive search of PubMed and EMBASE to identify cohort studies examining the association between uveitis and psoriatic disease psoriasis and/or psoriatic arthritis (PsA). We used a random-effects model to calculate the pooled relative risks (RRs) adjusted for confounders, along with the 95% confidence intervals (CIs).
This Meta-analysis included a total of 6 studies and a maximum of 80 178 648 participants. Compared with non-psoriatic controls, uveitis risk was significantly elevated in patients with psoriasis (RR=1.49; 95%CI: 1.08-2.07), and PsA (RR=3.16; 95%CI: 2.16-4.63). Furthermore, pre-existing uveitis was associated with a significantly increased risk of psoriasis (RR=1.62; 95%CI: 1.44-1.83), and PsA (RR=4.44; 95%CI: 3.52-5.60).
The results of this systematic review and Meta-analysis suggest an overall positive bidirectional association between uveitis and psoriatic disease (psoriasis and PsA), warranting increased awareness among clinicians involved in the management of these two conditions. Therefore, there remains a need for more detailed studies of the possible common pathogenesis of psoriatic disease and uveitis.
A number of virus-encoded microRNAs have been shown to play important roles in virus replication and virus-host interactions, although the expression and function of miR-TAR-3p derived from the human ...immunodeficiency virus type 1 (HIV-1) TAR element remain controversial. In this study, miR-TAR-3p was detected in human peripheral blood monocyte-derived macrophages (MDMs) infected by HIV-1. Overexpression of miR-TAR-3p impaired viral replication, while inhibition of miR-TAR-3p enhanced it. Additionally, miR-TAR-3p repressed viral transcription and replication by targeting the TAR element in the HIV-1 5’-LTR in a sequence-specific manner. These results confirm the presence of miR-TAR-3p in HIV-1-infected MDMs and suggest that its function might be used as a mechanism to modulate HIV-1 replication through the expression of a negative regulatory factor.
Hec1 (highly expressed incancer) plays essential roles in chromosome segregation by interacting through its coiled-coil domains with several proteins that modulate the G2/M phase. Hec1 localizes to ...kinetochores, and its inactivation either by genetic deletion or antibody neutralization leads to severe and lethal chromosomal segregation errors, indicating that Hec1 plays a critical role in chromosome segregation. The mechanisms by which Hec1 is regulated, however, are not known. Here we show that human Hec1 is a serine phosphoprotein and that it binds specifically to the mitotic regulatory kinase Nek2 during G2/M. Nek2 phosphorylates Hec1 on serine residue 165, both in vitro and in vivo. Yeast cells are viable without scNek2/Kin3, a close structural homolog of Nek2 that binds to both human and yeast Hec1. When the same yeasts carry an scNek2/Kin3 (D55G) or Nek2 (E38G) mutation to mimic a similar temperature-sensitive nima mutation inAspergillus, their growth is arrested at the nonpermissive temperature, because the scNek2/Kin3 (D55G) mutant binds to Hec1 but fails to phosphorylate it. Whereas wild-type human Hec1 rescues lethality resulting from deletion of Hec1 in Saccharomyces cerevesiae, a human Hec1 mutant or yeast Hec1 mutant changing Ser165 to Ala or yeast Hec1 mutant changing Ser201 to Ala does not. Mutations changing the same Ser residues to Glu, to mimic the negative charge created by phosphorylation, partially rescue lethality but result in a high incidence of errors in chromosomal segregation. These results suggest that cell cycle-regulated serine phosphorylation of Hec1 by Nek2 is essential for faithful chromosome segregation.
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