Inflammation can induce cognitive dysfunction in patients who undergo surgery. Previous studies have demonstrated that both acute peripheral inflammation and anaesthetic insults, especially ...isoflurane (ISO), are risk factors for memory impairment. Few studies are currently investigating the role of ISO under acute peri-inflammatory conditions, and it is difficult to predict whether ISO can aggravate inflammation-induced cognitive deficits. HDACs, which are essential for learning, participate in the deacetylation of lysine residues and the regulation of gene transcription. However, the cell-specific mechanism of HDACs in inflammation-induced cognitive impairment remains unknown.
Three-month-old C57BL/6 mice were treated with single versus combined exposure to LPS injected intraperitoneally (i.p.) to simulate acute abdominal inflammation and isoflurane to investigate the role of anaesthesia and acute peripheral inflammation in cognitive impairment. Behavioural tests, Western blotting, ELISA, immunofluorescence, qRT-PCR, and ChIP assays were performed to detect memory, the expressions of inflammatory cytokines, HDAC2, BDNF, c-Fos, acetyl-H3, microglial activity, Bdnf mRNA, c-fos mRNA, and Bdnf and c-fos transcription in the hippocampus.
LPS, but not isoflurane, induced neuroinflammation-induced memory impairment and reduced histone acetylation by upregulating histone deacetylase 2 (HDAC2) in dorsal hippocampal CaMKII
neurons. The hyperexpression of HDAC2 in neurons was mediated by the activation of microglia. The decreased level of histone acetylation suppressed the transcription of Bdnf and c-fos and the expressions of BDNF and c-Fos, which subsequently impaired memory. The adeno-associated virus ShHdac2, which suppresses Hdac2 after injection into the dorsal hippocampus, reversed microglial activation, hippocampal glutamatergic BDNF and c-Fos expressions, and memory deficits.
Reversing HDAC2 in hippocampal CaMKII
neurons exert a neuroprotective effect against neuroinflammation-induced memory deficits.
Identifying novel drug targets to overcome resistance to tyrosine kinase inhibitors (TKIs) and eradicating leukemia stem/progenitor cells are required for the treatment of chronic myelogenous ...leukemia (CML). Here, we show that ubiquitin-specific peptidase 47 (USP47) is a potential target to overcome TKI resistance. Functional analysis shows that USP47 knockdown represses proliferation of CML cells sensitive or resistant to imatinib in vitro and in vivo. The knockout of Usp47 significantly inhibits BCR-ABL and BCR-ABL
-induced CML in mice with the reduction of Lin
Sca1
c-Kit
CML stem/progenitor cells. Mechanistic studies show that stabilizing Y-box binding protein 1 contributes to USP47-mediated DNA damage repair in CML cells. Inhibiting USP47 by P22077 exerts cytotoxicity to CML cells with or without TKI resistance in vitro and in vivo. Moreover, P22077 eliminates leukemia stem/progenitor cells in CML mice. Together, targeting USP47 is a promising strategy to overcome TKI resistance and eradicate leukemia stem/progenitor cells in CML.
Although basic research has suggested that oxidized low-density lipoprotein (ox-LDL) is involved in the pathogenesis of atherosclerosis, population observational studies have yielded conflicting ...results about the association between circulating ox-LDL and atherosclerotic cardiovascular disease (ASCVD). Therefore, we performed a systematic review and meta-analysis of currently available observational studies to verify the association between circulating ox-LDL and ASCVD.
We systematically searched PubMed and the Cochrane Library from their inception to March 27, 2017, for nested case-control studies, case-cohort studies, and prospective cohort studies on the relationship between ox-LDL and ASCVD. Studies that did not assess the hazard ratio, relative risk, or odds ratio of ox-LDL or did not adjust for other risk factors, or those without examination of ox-LDL before collection of ASCVD occurrences were excluded. The summarized effect size was combined using fixed effect models. Subgroup analyses were performed on the basis of study quality, study design, definition of ASCVD events, effect size types, types of ox-LDL assay, ox-LDL contrast level, and whether low-density lipoprotein cholesterol was adjusted in a multivariate model.
A total of 12 included studies consisted of 3 nested case-control studies, 1 case-cohort study, 5 hospital-based cohort studies, and 3 community-based cohort studies. The summary effect size of increased circulating ox-LDL was 1.79 (95% confidence interval, 1.56-2.05) for ASCVD. Similar associations were shown in all subgroups.
Our findings indicate that increased levels of circulating ox-LDL are associated with clinical ASCVD events. Further well designed community-based cohort studies or intervention studies are needed to confirm our findings.
Même si la recherche fondamentale suggère que les lipoprotéines de faible densité (LDL) oxydées jouent un rôle dans la pathogenèse de l’athérosclérose, des études observationnelles de population ont abouti à des résultats contradictoires en ce qui concerne le lien entre les LDL oxydées circulantes et les maladies cardiovasculaires (MCV) athéroscléreuses. C’est pourquoi nous avons effectué une revue et une méta-analyse systématiques des études observationnelles disponibles à ce jour pour vérifier le lien entre les LDL oxydées circulantes et les MCV athéroscléreuses.
Nous avons réalisé une recherche systématique dans PubMed et la bibliothèque Cochrane à partir du moment de leur création jusqu’au 27 mars 2017, et ce, afin de trouver des études de cas-témoins emboîtés, des études cas-cohortes et des études de cohortes prospectives évaluant le lien entre les LDL oxydées circulantes et les MCV athéroscléreuses. Les études suivantes ont été exclues : celles qui n’ont pas évalué le rapport des risques instantanés, le risque relatif ou le rapport de cotes relativement aux LDL oxydées; celles qui n’ont pas ajusté les résultats en fonction d’autres facteurs de risque; ou celles qui n’ont pas évalué le taux de LDL oxydées avant de relever la survenue de manifestations attribuables aux MCV athéroscléreuses. L’ampleur globale de l’effet a été obtenue en utilisant des modèles à effets fixes. Des analyses de sous-groupes ont été réalisées en se basant sur la qualité de l’étude, la méthodologie, la définition des manifestations attribuables aux MCV athéroscléreuses, le type d’ampleur de l’effet, le type d’analyses pour mesurer le taux de LDL oxydées, le niveau de contraste lié aux LDL oxydées, et si le taux de cholestérol LDL a été ajusté selon un modèle multivarié.
Au total, 12 études ont été prises en compte, soit 3 études de cas-témoins emboîtés, 1 étude cas-cohortes, 5 études de cohortes hospitalières et 3 études de cohortes communautaires. L’ampleur de l’effet globale de l’augmentation des LDL oxydées dans le sang était de 1,79 (intervalle de confiance à 95 % : 1,56-2,05) pour les MCV athéroscléreuses. Un lien similaire a été observé dans tous les sous-groupes.
Nos résultats montrent qu’un taux circulant élevé de LDL oxydées est associé à des manifestations cliniques attribuables aux MCV athéroscléreuses. D’autres études de cohortes communautaires ou études d’intervention bien conçues seront nécessaires pour confirmer nos résultats.
A
bstract
In this paper we study the recently proposed tensor networks/AdS correspondence. We found that the Coxeter group is a useful tool to describe tensor networks in a negatively curved space. ...Studying generic tensor network populated by perfect tensors, we find that the physical wave function generically do not admit any connected correlation functions of local operators. To remedy the problem, we assume that wavefunctions admitting such semi-classical gravitational interpretation are composed of tensors close to, but not exactly perfect tensors. Computing corrections to the connected two point correlation functions, we find that the leading contribution is given by structures related to geodesics connecting the operators inserted at the boundary physical dofs. Such considerations admit generalizations at least to three point functions. This is highly suggestive of the emergence of the analogues of Witten diagrams in the tensor network. The perturbations alone however do not give the right entanglement spectrum. Using the Coxeter construction, we also constructed the tensor network counterpart of the BTZ black hole, by orbifolding the discrete lattice on which the network resides. We found that the construction naturally reproduces some of the salient features of the BTZ black hole, such as the appearance of RT surfaces that could wrap the horizon, depending on the size of the entanglement region
A
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Macrophages with tumor-tropic migratory properties can serve as a cellular carrier to enhance the efficacy of anti neoplastic agents. However, limited drug loading (DL) and insufficient drug release ...at the tumor site remain the main obstacles in developing macrophage-based delivery systems. In this study, we constructed a biomimetic delivery system (BDS) by loading doxorubicin (DOX)-loaded reduced graphene oxide (rGO) into a mouse macrophage-like cell line (RAW264.7), hoping that the newly constructed BDS could perfectly combine the tumor-tropic ability of macrophages and the photothermal property of rGO.
At the same DOX concentration, the macrophages could absorb more DOX/PEG-BPEI-rGO than free DOX. The tumor-tropic capacity of RAW264.7 cells towards RM-1 mouse prostate cancer cells did not undergo significant change after drug loading in vitro and in vivo. PEG-BPEI-rGO encapsulated in the macrophages could effectively convert the absorbed near-infrared light into heat energy, causing rapid release of DOX. The BDS showed excellent anti-tumor efficacy in vivo.
The BDS that we developed in this study had the following characteristic features: active targeting of tumor cells, stimuli-release triggered by near-infrared laser (NIR), and effective combination of chemotherapy and photothermotherapy. Using the photothermal effect produced by PEG-BPEI-rGO and DOX released from the macrophages upon NIR irradiation, MAs-DOX/PEG-BPEI-rGO exhibited a significant inhibitory effect on tumor growth.
To improve the separation efficiency of parallel hydrocyclones, a new type of common liquid hopper was designed. The separation efficiency of conventional parallel hydrocyclones and those parallel ...with liquid hoppers were measured experimentally and the influence of common liquid hopper on the flow field analyzed using FLUENT software. The results showed that the efficiency of the parallel hydrocyclones group with liquid hoppers was higher than that of the conventional group, with the maximum efficiency increased by 2.2% and average efficiency increased by 2.1%. The fishhook effect in the efficiency curves was clearly weakened. The separation efficiency of particles between 3 and 10 μm was clearly improved. Compared with the conventional parallel connection, a liquid hopper made the air core in the parallel hydrocyclone group disappear. Meanwhile. the locus of zero vertical velocities was closer to the inside of the hydrocyclone and the free vortex height higher, which make the separation space larger. In addition, parallel vortices in the liquid hopper possessed an inherent self-stability and restricted each other, which caused the swing amplitude of the vortex system center with liquid hopper to be smaller than that of the single vortex center. Therefore, it was demonstrated here that the common liquid hopper improved the separation efficiency of parallel hydrocyclones.
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•Design a new type of parallel hydrocyclones with common liquid hopper.•The common liquid hopper can improve the separation efficiency.•The common liquid hopper eliminates the air core and make separation space larger.•The common liquid hopper makes self-stability of the vortex system stronger.
Summary
To study the physicochemical properties of sesame paste produced by a novel process technology—ball milling, the effects of different ball milling times (8, 16, 24, 32, and 40 min) at 650 rpm ...on particle size, texture, rheological properties, volatile compounds, consumer sensory evaluation, and microstructure of sesame paste were investigated. The results showed that ball milling has no significant differences in proximate composition and colour of sesame paste, but the D90 value of particle size decreased to 32.04 μm. Compared to others, the sesame paste ball‐milled for 8 min has the highest viscosity of 277.195 g·s. The sesame paste obtained by ball milling for 32 and 40 min produced 55 and 56 volatile compounds, respectively. Regardless of male and female, sesame paste obtained by ball milling for 24, 32, and 40 min have high overall acceptability. This investigation shows that ball milling is a new technology of potentially great value in the industrial production of sesame paste, which can be used to produce high‐quality sesame paste with specific characteristics.
To study the physicochemical properties of sesame paste produced by a novel process technology—ball milling, the effects of different ball milling times (8, 16, 24, 32, and 40 min) at 650 rpm on particle size, texture, rheological properties, volatile compounds, consumer sensory evaluation, and microstructure of sesame paste were investigated. This investigation shows that ball milling is a new technology of potentially great value in the industrial production of sesame paste, which can be used to produce high‐quality sesame paste with specific characteristics.
Increasing circulating adiponectin levels in the first to the second trimester could decrease the risk of incident GDM.
To quantitatively synthesize evidence from prospective observational studies ...regarding the mean levels of circulating adiponectin in patients with gestational diabetes mellitus (GDM) and the association between adiponectin levels and GDM risk.
PubMed, EMBASE and Web of Science were searched from their inception until November 8th, 2022, for nested case-control studies and cohort studies. Random-effect models were applied to the synthesized effect sizes. The difference in circulating adiponectin levels between the GDM and control groups was measured using the pooled standardized mean difference (SMD) and 95% confidence interval (CI). The relationship between circulating adiponectin levels and GDM risk was examined using the combined odds ratio (OR) and 95% CI. Subgroup analyses were performed according to the study continent, GDM risk in the study population, study design, gestational weeks of circulating adiponectin detection, GDM diagnostic criteria, and study quality. Sensitivity and cumulative analyses were performed to evaluate the stability of the meta-analysis. Publication bias was assessed by funnel plots and Egger's test.
The 28 studies included 13 cohort studies and 15 nested case-control studies, containing 12,256 pregnant women in total. The mean adiponectin level in GDM patients was significantly lower than in controls (SMD = −1.514, 95% CI = −2.400 to −0.628, p = .001, I
2
= 99%). The risk of GDM was significantly decreased among pregnant women with increasing levels of circulating adiponectin (OR = 0.368, 95% CI = 0.271-0.500, p < .001, I
2
=83%). There were no significant differences between the subgroups.
Our findings indicate that increasing circulating adiponectin levels were inversely associated with the risk of GDM. Given the inherent heterogeneity and publication bias of the included studies, further well-designed large-scale prospective cohort or intervention studies are needed to confirm our finding.
Aims: To investigate the association between circulating oxidized low-density lipoprotein (ox-LDL) levels and progression of subclinical atherosclerosis and to examine whether this link is ...independent of other low-density lipoprotein (LDL)-related parameters.Methods: Totally, 804 subjects who were free of cardiovascular disease at baseline completed risk factor surveys and carotid ultrasound measurements in 2002 and 2012. Modified Poisson regression was performed to examine the association between baseline serum ox-LDL levels and the 10-year risk of progression of carotid atherosclerosis which was defined as the development of at least one new plaque in a previously plaque-free carotid segment at re-examination.Results: The mean age of the subjects was 58.6±7.7 years at baseline and 43.3% were men. A total of 504 (62.7%) subjects had carotid plaque progression at re-examination. Subjects in the intermediate and highest tertiles of ox-LDL had a significantly higher adjusted risk of atherosclerosis progression than those in the lowest tertile relative risk (95% confidence interval) 1.17 (1.01–1.34) for the intermediate tertile and 1.23 (1.07–1.42) for the highest tertile. This association was independent of baseline levels of LDL-C, total LDL particle number, and small LDL particle number.Conclusion: This study demonstrates that serum ox-LDL levels predict 10-year progression of subclinical atherosclerosis. Moreover, this effect is independent of the cholesterol content, the number, and the size of LDL particles.
This experiment explored the effects of single application of seven types of slow- and controlled-release fertilizers on rice yield and various population characteristics. Based on a study of the ...nitrogen (N) release characteristics of these fertilizers, pot experiments were conducted in 2018 and 2019 with split fertilization (CK, urea applied split equally at basal and panicle initiation stages, respectively) as control, which assessed the effects on SPAD value, yield and yield components, dynamic changes of rice tillers and dry matter accumulation. The results showed that the N release characteristics of different types of slow- and controlled-release fertilizers were significantly different. Polymer-coated urea (PCU) showed a controlled-release mode and provided sustained release throughout the whole growth stages. Sulfur-coated urea (SCU) exhibited a slow-release mode, providing insufficient release at the middle and late stages. Urease inhibitor urea (AHA) and urea-formaldehyde (UF) yielded a rapid-release mode, with an explosive N release at the early stage and no release at the middle and late stages. These results showed that PCU delayed the peak seedling stage. Compared with CK, dry matter accumulation and SPAD showed no significant differences, and due to the continuous release of N throughout the growth stages, rice yield, spikelets per panicle, seed setting rate, and 1 000-grain weight were all increased. Owing to the lack of N supply at the late stage and the low number of spikelets, SCU led to a reduction of rice yield, which is nevertheless not statistically significant. AHA and UF were susceptible to environmental factors and had varying effects on rice yield. The results of this experiment indicated that given a fixed amount of N applied in a pot, the stronger the N supply capacity and the longer the effective duration time of the fertilizer, the higher the dry matter accumulation at the late growth stage, and the higher the rice yield.
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