Isoflurane (Iso) is a commonly used inhalational anesthetic and is associated with the incidence of postoperative cognitive dysfunction (POCD). Cannabinoid receptor 2 (CB2R) was previously reported ...to have a promising neuroprotective function in cases of POCD, but the specific mechanisms have remained to be fully explored. The aim of the present study was to investigate the effect of CB2R deficiency on spatial cognitive performance in adult mice exposed to Iso. A total of 20 adult CB2R knockout (KO) and 20 wildtype (WT) mice were exposed to Iso (1.4% in oxygen for 4 h) or 100% oxygen. The Morris water maze (MWZ) test was performed 10 days after Iso exposure. Immunofluorescence staining and reverse transcription-quantitative PCR were performed to assess the expression of microglial marker ionized calcium-binding adaptor molecule-1 (Iba1) and the mRNA expression levels of microglial phenotype markers (M1: Interleukin-6, tumor necrosis factor-alpha, inducible nitric oxide synthase; M2: Chitinase-3 like protein) in the hippocampus. Changes in hippocampal neurogenesis and neuroplasticity were assessed by 5-bromodeoxyuridine (BrdU) immunostaining and Golgi staining. Compared with control mice, WT Iso-exposed mice had impaired spatial performance in the MWZ test. Furthermore, hippocampal Iba1 immunoreactivity and the number of microglial branches were notably increased in Iso-exposed WT mice. This was paralleled by significant upregulation of M1-associated markers and downregulation of M2-associated markers in the hippocampus. An obviously reduced number of BrdU+ neurons and decreased spine density were observed in WT Iso-exposed mice compared with control mice. Of note, CB2R deficiency exacerbated the spatial cognition impairment induced by Iso in the MWZ test. The alterations in the activation, morphology and M1 polarization of microglia, the number of BrdU+ neurons and spine density were more pronounced in CB2R-deficient Iso-exposed KO mice than in WT Iso-exposed mice. These results suggested that CB2R has a crucial role in Iso-induced cognitive impairment, which may be related to changes in hippocampal neuroinflammation, neurogenesis and neuroplasticity. Key words: cannabinoid receptor 2, isoflurane, cognition, neuroinflammation, neurogenesis, neuroplasticity
Liver cancer is the fifth most common malignant tumor in terms of incidence and the third leading cause of cancer-related mortality globally. Hepatocellular carcinoma (HCC) is the most common type of ...primary liver cancer. Although great progress has been made in surgical techniques, hepatic artery chemoembolization, molecular targeting and immunotherapy, the prognosis of liver cancer patients remains very poor. N
-methyladenosine (m
A) is the most abundant internal RNA modification in eukaryotic cells and regulates various stages of the RNA life cycle. Many studies have reported that the abnormal expression of m6A-related regulators in HCC represent diagnostic and prognostic markers and potential therapeutic targets. In this review, firstly, we introduce the latest research on m
A-related regulators in detail. Next, we summarize the mechanism of each regulator in the pathogenesis and progression of HCC. Finally, we summarize the potential diagnostic, prognostic and therapeutic value of the regulators currently reported in HCC.
Aiming to achieve resonance suppression of a controllable mechanism welding robot end using dynamic modeling and experimental verification, this paper applies a central composite design methodology ...to optimize suppression resonance using three variables: excitation source, rod stiffness and damping. Considering the coupling effects of the excitation source, member stiffness and damping, a combination optimization is carried out, and the optimal control result of the end is obtained, for which the optimized peak amplitudes are significantly reduced. The research provides an important technical basis for the dynamic design and resonance suppression control of controllable welding robot mechanisms.
It was confirmed that simulated microgravity (SMG) led to ultrastructural alterations and apoptosis in many types of microvascular endothelial cells. However, whether SMG would also affect choroidal ...vascular endothelial cells (CVECs) remains unknown. This study was designed to investigate the effects of SMG on ultrastructure and apoptosis of CVECs.
The rotary cell culture system (RCCS) was utilized to simulate microgravity condition. Human CVECs were cultured under normal gravity (NG) or SMG condition for 3 days. The ultrastructure was viewed under transmission electron microscopy, and the organization of F-actin was observed by immunofluorescence staining. Additionally, the apoptosis percentage was calculated using flow cytometry. Moreover, the mRNA and protein expression of BAX, Bcl-2, Caspase3, Cytochrome C, p-AKT, and p-PI3K were detected with quantitative PCR and Western blot at different exposure time.
In the SMG group, CVECs presented with a shrunk cell body, chromatin condensation and margination, mitochondria vacuolization, and apoptotic bodies. The amount of F-actin decreased, and the filaments of F-actin were sparse or even partly discontinuous after cultivation under SMG for 72 h. The proportions of apoptotic CVECs in SMG groups at 24 and 72 h were significantly higher than those in the NG group (
< 0.001). The mRNA and protein expression of Bax, Caspase3, and Cytochrome C of CVECs in SMG groups at 24 and 72 h significantly increased than those of the NG group, respectively (
< 0.001). The alterations of p-AKT and p-PI3K protein expression possessed similar trends. On the contrary, the mRNA and protein expression of Bcl-2 in CVECs under SMG at 24 and 72 h were significantly less than that of the NG group, respectively (
< 0.001).
Simulated microgravity conditions can lead the alterations of the F-actin structure and apoptosis of CVECs. The Bcl-2 apoptosis pathway and PI3K/AKT pathway may participate in the damage of CVECs caused by SMG.
The present study examined the effects of wearable visual cues, provided by a wearable laser device, on the gait pattern and stability in patients with Parkinson's disease (PD). In total, 18 patients ...with a clinical diagnosis of idiopathic PD (Hoehn and Yahr stage II-III) and 18 healthy controls were included. The main outcome measures included spatiotemporal parameters, sagittal plane kinematic parameters of joints in lower limbs, and dynamic center of pressure (COP) parameters. Significant intra-group improvement in gait parameters was observed in PD patients. Compared with that at baseline, the gait pattern improved in PD patients under the cued condition, with longer stride length and higher toe clearance, as well as shortening of double stance phase, especially the stride length, double stance phase and toe clearance were not significantly different between cued condition and healthy control groups. In kinematics, the ankle peak dorsiflexion in swing phase and the hip range of motion (ROM) in gait cycle was significantly improved in PD patients with visual cues and close to healthy controls. Decreased anteroposterior (AP) position of COP improved gait stability in patients with PD under the cued condition. Multiple linear regression analysis showed that the AP position has a negative correlation with ankle peak dorsiflexion in swing phase. Pearson's correlation coefficients showed that the minimum toe clearance (Mini TC) was positively correlated with the ankle peak dorsiflexion in swing phase. The immediate effect of wearable visual cues improved the gait pattern and stability in PD patients, suggesting that it may be effective when applied as an alternative technique in rehabilitation training for PD patients.
Hua (
) is one of the most important herbs in traditional Chinese medicine. Polysaccharides in
plants comprise a class of important secondary metabolites and exhibit a broad range of pharmacological ...functions.
In order to identify genes involved in polysaccharide biosynthesis, we performed RNA sequencing analysis of leaf, root, and rhizome tissues of
. A total of 164,573 unigenes were obtained by assembling transcripts from all three tissues and 86,063 of these were annotated in public databases. Differentially expressed genes (DEGs) were determined based on expression profile analysis, and DEG levels in rhizome tissues were then compared with their counterparts in leaf and root tissues. This analysis revealed numerous genes that were either up-regulated or uniquely expressed in the rhizome. Multiple genes encoding important enzymes, such as UDP glycosyltransferases (UGTs), or transcription factors involved in polysaccharide biosynthesis were identified and further analyzed, while a few genes encoding key enzymes were experimentally validated using quantitative real-time PCR.
Our results substantially expand the public transcriptome dataset of
and provide valuable clues for the identification of candidate genes involved in metabolic pathways.
The modal and vibration-noise response characteristics of plate structures are closely related to their boundary effects, and the analytical modeling and solution of the dynamics of plate structures ...with complex boundary conditions can reveal mechanisms of the influence of the boundary structure parameters on the modal characteristics. This paper proposes a new method for dynamic modeling of rectangular plates with periodic boundary conditions based on the energy equivalence principle (mixed-variable variational principle) of equating complex boundary “geometric constraints” to “mathematical physical constraints”, taking a rectangular plate structure with periodic boundaries commonly used in engineering as the object. First, the boundary external potential energy of the periodic boundary rectangular plate is obtained by equating the bending moment and deflection to the boundary conditions. Next, we establish the total potential energy model, the amplitude boundary equation, as well as the frequency equation of the periodic boundary rectangular plate in turn. Solving by numerical method, the natural frequency of the theoretical model is obtained. The validity of the theoretical model is then verified by modal test experiments. Finally, the law of the parameters such as the form of boundary constraint, the number of periods, and the clamp support ratio on the natural frequency of the rectangular plate is investigated. The results show that the natural frequency of the rectangular plate is closely related to the boundary form and period distribution of the plate. The modal frequencies of the plate structure can be tuned by the design of the boundary conditions for a certain size of the plate structure. The research in this paper provides a theoretical and technical basis for the vibration noise control of complex boundary plate structures.
A novel sansanmycin analogue, sansanmycin Q (1), was identified by genome mining from the fermentation broth of Streptomyces sp. SS (CPCC 200442). In comparison with other sansanmycin compounds, ...sansanmycin Q has an extra glycine residue at the N-terminus of the pseudopeptide backbone. The additional glycine was proved to be assembled to sansanmycin A by SsaB, a tRNA-dependent aminoacyltransferase, based on the results of rescrutiny of sansanmycin biosynthetic gene cluster, and then overexpression and knockout of ssaB in the wild-type strain. The structure of sansanmycin Q was assigned by interpretation of NMR and mass spectral data. The results of the bioassay disclosed that sansanmycin Q exhibited more potency against Mycobacterium tuberculosis H
Rv and a rifampicin- and isoniazid-resistant strain than sansanmycin A.
The role of HHLA2, a new immune checkpoint ligand, is gradually being elucidated in various solid tumours. However, its role in ovarian cancer remains unclear; thus, its expression profile and ...clinical significance in ovarian cancer must be examined.
We performed immunohistochemistry to examine HHLA2 expression in 64 ovarian cancer tissues and 16 normal ovarian tissues. The relationships between HHLA2 expression and clinicopathological features, prognosis, and CD8
tumour-infiltrating lymphocytes (TILs) in patients were analysed. Additionally, the Cancer Cell Line Encyclopedia database was used to analyse the correlation between HHLA2 expression and PD-L1 or B7x expression. Furthermore, the biological function of HHLA2 in ovarian cancer cells was initially explored.
Only 17.2% of ovarian cancer patients showed HHLA2 expression, which was significantly associated with the differentiation of ovarian cancer cells (p = 0.027), and well-differentiated tumours expressed higher levels of HHLA2. The density of CD8
TIL was associated with increased HHLA2 expression (p = 0.017), and the CD8
TIL count was higher in the HHLA2-positive group than that in the HHLA2-negative group (p = 0.023). Moreover, multivariate analysis identified HHLA2 expression as an independent prognostic factor that predicted improved survival (p = 0.049; HR = 0.156; 95% CI = 0.025-0.992). Additionally, we also found that overexpressing HHLA2 inhibited the proliferation of ovarian cancer cells.
HHLA2 is associated with tumour differentiation and high CD8
TIL levels; and predicts improved survival in ovarian cancer. Along with previously reported findings that HHLA2 behaves as a co-stimulatory ligand, our study suggests that the loss of HHLA2 may contribute to the immunosuppressive microenvironment and progression of ovarian cancer.
Ischemic stroke is characterized by loss of brain function because of cerebral ischemia. Evidence has been shown that miR-217-5p is significantly downregulated in infarcted brain areas following ...focal cerebral ischemia. However, the role of miR-217-5p in ischemic stroke is still unclear. To mimic ischemia/reperfusion (I/R) injury conditions in vitro, SH-SY5Y cells were treated with oxygen–glucose deprivation/reperfusion (OGD/R). Our data found that PTEN was the directly target of miR-217-5p in SH-SY5Y cells. The level of miR-217-5p was significantly decreased, while the level of PTEN was notably increased in SH-SY5Y cells following OGD/R treatment. Overexpression of miR-217-5p markedly promoted the proliferation and cell cycle progression, and inhibited apoptosis in OGD/R-treated SH-SY5Y cells. In addition, overexpression of miR-217-5p significantly decreased the expressions of PTEN and FOXO1, but increased the expression of p-Akt in OGD/R-treated SH-SY5Y cells. Moreover, methylation specific PCR (MSP) results indicated the CpG islands in the promoter region of miR-217-5p were hypermethylated in SH-SY5Y cells under OGD/R. Meanwhile, the DNA methylation of miR-217-5p promoter region decreased expression of miR-217-5p. Our data indicated that miR-217-5p could attenuate ischemic injury by inhibiting PTEN. In addition, DNA methylation-mediated silencing of miR-217-5p may serve as a promising therapeutic target of ischemic stroke.
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