Effects of postweaning cadmium exposure on socioemotional behaviors in adolescent male mice.

Exposure to cadmium (Cd), a toxic heavy metal classified as an environmental endocrine disruptor, can exert significant toxicity in both animals and humans. However, the potential effects of Cd exposure on socioemotional behaviors are still poorly understood, as are the underlying mechanisms. In the present study, employing a series of behavioral tests as well as 16 S rRNA sequencing analysis, we investigated the long-term effects of Cd exposure on socioemotional behaviors and their associated mechanisms in mice based on the brain-gut interaction theory. The results showed that postweaning exposure to Cd reduced the ability to resist depression, decreased social interaction, subtly altered sexual preference, and changed the composition of the gut microbiota in male mice during adolescence. These findings provided direct evidence for the deleterious effects of exposure to Cd in the postweaning period on socioemotional behaviors later in adolescence, and suggested that these effects of Cd exposure may be linked to changes in the gut microbiota.

Long noncoding RNA lncPostn links TGF-ß and p53 signaling pathways to transcriptional regulation of cardiac fibrosis.

Cardiac fibroblasts are essential for the homeostasis of the extracellular matrix, whose remodeling in many cardiovascular diseases leads to fibrosis. Long noncoding RNAs (lncRNAs) are associated with cardiac pathologies, but their functions in cardiac fibroblasts and contributions to cardiac fibrosis remain unclear. Here, we aimed to identify fibroblast-enriched lncRNAs essential in myocardial infarction (MI)-induced fibrosis and explore the molecular mechanisms responsible for their functions. Global lncRNA profiling was performed in post-MI mouse heart ventricles and transforming growth factor-ß (TGF-ß)-treated primary cardiac fibroblasts and confirmed in published data sets. We identified the cardiac fibroblast-enriched lncPostn, whose expression is stimulated in cardiac fibrosis induced by MI and the extracellular growth factor TGF-ß. The promoter of lncPostn contains a functional TGF-ß response element, and lncPostn knockdown suppresses TGF-ß-stimulated cardiac fibroblast activation and improves cardiac functions post-MI. LncPostn stabilizes and recruits EP300 to the profibrotic periostin's promoter, representing a major mechanism for its transcriptional activation. Moreover, both MI and TGF-ß enhance lncPostn expression while suppressing the cellular growth gatekeeper p53. TGF-ß and p53 knockdown-induced profibrotic gene expression and fibrosis occur mainly through lncPostn and show additive effects. Finally, levels of serum lncPostn are significantly increased in patients' postacute MI and show a strong correlation with fibrosis markers, revealing a potential biomarker of cardiac fibrosis. Our findings identify the fibroblast-enriched lncPostn as a potent profibrotic factor, providing a transcriptional link between TGF-ß and p53 signaling pathways to regulate fibrosis in cardiac fibroblasts.NEW & NOTEWORTHY Cardiac fibroblasts are essential for the homeostasis of the extracellular matrix, whose remodeling in many cardiovascular diseases leads to fibrosis. Long noncoding RNAs are functional and contribute to the biological processes of cardiovascular development and disorders. Our findings identify the fibroblast-enriched lncPostn as a potent profibrotic factor and demonstrate that serum lncPostn level may serve as a potential biomarker of human cardiac fibrosis postacute myocardial infarction.

Quality evaluation of metabolic and bariatric surgical guidelines.

Objective: To evaluate the quality of surgical guidelines on bariatric/metabolic surgery. Methods: Four independent reviewers used the AGREE II (The Appraisal of Guidelines for Research and Evaluation II) tool to assess the methodological quality of the included guidelines and conducted a comparative analysis of the main recommendations for surgical methods of these guidelines. Results: Nine surgical guidelines were included in this study. Five articles with AGREE II scores over 60% are worthy of clinical recommendation. The field of rigor of development was relatively low, with an average score of 50.82%. Among 15 key recommendations and the corresponding best evidence in the guidelines, only 4 key recommendations were grade A recommendations. Conclusions: The quality of metabolic and bariatric guidelines is uneven, and there is much room for improvement.

A short peptide exerts neuroprotective effects on cerebral ischemia-reperfusion injury by reducing inflammation via the miR-6328/IKKß/NF-κB axis.

BACKGROUND: Despite considerable efforts, ischemic stroke (IS) remains a challenging clinical problem. Therefore, the discovery of effective therapeutic and targeted drugs based on the underlying molecular mechanism is crucial for effective IS treatment. METHODS: A cDNA-encoding peptide was cloned from RNA extracted from Rana limnocharis skin, and the mature amino acid sequence was predicted and synthesized. Hemolysis and acute toxicity of the peptide were tested. Furthermore, its neuroprotective properties were evaluated using a middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and an oxygen-glucose deprivation/reperfusion (OGD/R) model in neuron-like PC12 cells. The underlying molecular mechanisms were explored using microRNA (miRNA) sequencing, quantitative real-time polymerase chain reaction, dual-luciferase reporter gene assay, and western blotting. RESULTS: A new peptide (NP1) with an amino acid sequence of 'FLPAAICLVIKTC' was identified. NP1 showed no obvious toxicities in vivo and in vitro and was able to cross the blood-brain barrier. Intraperitoneal administration of NP1 (10 nmol/kg) effectively reduced the volume of cerebral infarction and relieved neurological dysfunction in MCAO/R model rats. Moreover, NP1 significantly alleviated the decrease in viability and increase in apoptosis of neuron-like PC12 cells induced by OGD/R. NP1 effectively suppressed inflammation by reducing interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels in vitro and in vivo. Furthermore, NP1 up-regulated the expression of miR-6328, which, in turn, down-regulated kappa B kinase ß (IKKß). IKKß reduced the phosphorylation of nuclear factor-kappa B p65 (NF-κB p65) and inhibitor of NF-κB (I-κB), thereby inhibiting activation of the NF-κB pathway. CONCLUSIONS: The newly discovered non-toxic peptide NP1 ('FLPAAICLVIKTC') exerted neuroprotective effects on cerebral ischemia-reperfusion injury by reducing inflammation via the miR-6328/IKKß/NF-κB axis. Our findings not only provide an exogenous peptide drug candidate and endogenous small nucleic acid drug candidate but also a new drug target for the treatment of IS. This study highlights the importance of peptides in the development of new drugs, elucidation of pathological mechanisms, and discovery of new drug targets.

CDKN2AIP-induced cell senescence and apoptosis of testicular seminoma are associated with CARM1 and eIF4ß.

Testicular seminoma is a relatively rare tumor which is mostly detected in male population aged from 15 to 35 years old. Although several molecular biomarkers have been identified to be associated with testicular seminoma pathogenesis, the exact mechanism for testicular seminoma progression remains largely unknown. CDKN2A interacting protein (CDKN2AIP) has previously been identified as a tumor suppressor in multiple malignant diseases. In this study, we aimed to further explore its role in testicular seminoma as well as the underlying molecular mechanisms. Retrospective testicular seminoma clinical samples, normal tissues, NTERA-2 cell line, and mouse xenograft models were used in this study. RT-qPCR, western blot analysis, immunofluorescence microscopy, Co-IP and IP-MS experiments were performed to detect the expression of CDKN2AIP and its interaction with CARM1 and eIF4ß. SA-ß-gal staining assay and H3K9me3 activity experiments were used to subsequently evaluate the cell senescence and apoptosis. Mouse xenograft animal model was used for in vivo study. The results showed that CDKN2AIP is highly expressed in normal testis samples, and is significantly suppressed in testicular seminoma clinical samples and cell line model. Up-regulation of CDKN2AIP is significantly associated with the inhibition of testicular seminoma tumor growth and the increase of cell senescence and apoptosis. CDKN2AIP exhibits anti-tumor activity by interacting with CARM1 and eIF4ß. CDKN2AIP induces testicular seminoma cell senescence by suppressing CARM1 expression and eIF4ß phosphorylation. The CDKN2AIP-CARM1 and CDKN2AIP-eIF4ß interactions, which induce tumor cell senescence and apoptosis, may be the potential druggable molecular pathways in testicular seminoma tumor pathogenesis and progression.

The Role of CD147 in Pathological Cardiac Hypertrophy Is Regulated by Glycosylation.

CD147, also known as EMMPRIN or basigin, is a transmembrane glycoprotein receptor that activates matrix metalloproteinases and promotes inflammation. CD147 function is regulated by posttranslational modifications of which glycosylation has attracted the most attention. In this study, we demonstrated that glycosylated CD147 was the dominant form in heart tissue, and its levels were markedly elevated in response to transverse aortic constriction (TAC). Adeno-associated virus 9-mediated, cardiac-specific overexpression of wild-type CD147 in mice significantly promoted pressure overload-induced pathological cardiac remodeling accompanied by augmented oxidative stress and ferroptosis. By contrast, mutations of CD147 glycosylation sites notably weakened these detrimental effects of CD147. Mechanistically, CD147 exacerbated TAC-induced pathological cardiac remodeling via direct binding with the adaptor molecule TRAF2 and subsequent activation of TAK1 signalling, which was dependent on glycosylation of CD147. Collectively, our findings provide the first evidence that CD147 promoted pathological cardiac remodeling and dysfunction in a glycosylation-dependent manner through binding the adaptor protein TRAF2 and activating the downstream TRAF2-TAK1 signalling pathway. Thus, glycosylation of CD147 may be a potent interventional target for heart failure treatment.

Effect of Operating Parameters on Oxidation Characteristics of Soot under the Synergistic Action of Soluble Organic Fractions and Ash.

Diesel particulate filter is used to reduce particulate matter (PM) emission due to the stringent emission standards. The accumulated PM has been oxidized by the periodical regeneration method to avoid pressure buildup. The innovation of this study is to explore the oxidation performance of Printex-U (PU), which is mixed with ash and soluble organic fractions, under different operating conditions. Different aspects of operating parameters, such as the oxygen ratio in an O2/N2 atmosphere, total flow rate, initial PU mass, and heating rate, on PU oxidation properties have been critically discussed using a thermogravimetric analyzer. The oxygen ratio in the O2/N2 atmosphere is positively correlated with the oxidation characteristics of PU. The comprehensive oxidation index (S ) of PU under the 20% O2/80% N2 atmosphere increases by 184% compared with the 10% O2/90% N2 atmosphere. When the initial PU mass is 3 mg, the combustion stability coefficient (R w) and S reach the best values, which are 55.53 × 105 and 2.03 × 107 %2min-2 ° C-3, respectively. With the increase in the heating rate, the oxidation properties of PU become sensible and deflagration occurs easily, so that 10 °C/min heating rate is the best option. This study provides a theoretical basis for the optimization design of diesel particulates during the regeneration process.

Influence of Different Thermal Aging Conditions on Soot Combustion with Catalyst by Thermogravimetric Analysis.

Diesel particulates are deposited in the diesel particulate filter and removed by the regeneration process. The Printex-U (PU) particles are simulated as the diesel soot to investigate the influence of thermal aging conditions on soot combustion performance with the addition of catalysts. The comprehensive combustion index S, combustion stability index Rw and peak temperature Tp are obtained to evaluate the combustion performance. Compared with the PU/Pt mixtures of different Pt contents (2 g/ft3, 3.5 g/ft3, and 5 g/ft3), the 10 g/ft3 Pt contents improve soot combustion with the outstanding oxygen absorption ability. When the weight ratio of PU/Pt mixture is 1:1, the promoted effect achieves the maximum degree. The S and Rw increase to 8.90 × 10-8 %2min-2°C-3 and 39.11 × 105, respectively, compared with pure PU. After the thermal aging process, the PU/Pt mixture with a 350 °C aging temperature for 10 h promotes the soot combustion the best when compared to pure PU particles. It is not good as the PU/Pt mixture without aging, because the inner properties of soot and Pt/Al2O3 catalyst may have been changed. The S and Rw are 9.07 × 10-8 %2min-2°C-3 and 38.39 × 105, respectively, which are close to the no aging mixture. This work plays a crucial role in understanding the mechanism of the comprehensive effect of soot and catalyst on soot combustion after the thermal aging process.

Effect of Different Aging Conditions on the Soot Oxidation by Thermogravimetric Analysis.

Diesel particulate filter is an effective device to reduce diesel particulate emission. The particles in diesel particulate filter are usually affected by the aging of high-temperature exhaust gas before the regeneration process. In order to investigate the effect of aging conditions on the soot oxidation process, the effect of aging temperature and aging time on the oxidation process of carbon black (Printex-U, PU) and the PU/catalyst/ash mixture are studied by thermogravimetric analysis. The aging PU particles have lower starting temperature, peaking temperature, ending temperature, and activation energy. Compared with the particles without aging, the PU particles with a 400 °C aging temperature and 20 h aging time are able to reduce the activation energy from 191.2 to 158 kJ/mol. Low aging temperatures (200-300 °C) and the catalyst have a certain synergistic effect on the improvement of PU oxidation activity. The PU/CeO2 mixture with a 300 °C aging temperature and 20 h aging time decreases the activation energy from 178.4 to the lowest 113.6 kJ/mol. The addition of CaSO4 in PU particles cannot stop the improvement of its oxidation activity by aging, but it reduces the effect of aging. This work is helpful to reveal the mechanism of aging on PU and the PU/catalyst/ash mixture in air environment.

Thermogravimetric analysis of soot combustion in the presence of ash and soluble organic fraction.

Soot (Printex U, PU) combustion in the presence of ash and soluble organic fraction (SOF) was studied by thermogravimetric analysis (TGA). The comprehensive combustion index, combustion stability index and peak temperature were collected to evaluate the combustion performance of soot/ash/SOF mixtures. Compared with SiO2, Fe2O3 and CaSO4 nanoparticles, ZnO nanoparticles efficiently accelerate soot combustion with excellent oxygen carrying abilities. When the weight ratio of the PU/ZnO mixture is 1 : 1, this acceleration effect is maximized in the soot combustion process. The comprehensive combustion and combustion stability indices increase from 0.667 × 10-7%2 min-2 °C-3 and 23.53 × 105 to 1.296 × 10-7%2 min-2 °C-3 and 39.53 × 105, compared to pure PU, respectively. Compared with the PU/ZnO mixture, the soot combustion had inferior results after adding two oils as the simulative SOF. The 15W lubricant had the minimum negative impact compared to 0# diesel fuel. The comprehensive combustion and combustion stability indices reach the maximum values of 1.074 × 10-7%2 min-2 °C-3 and 33.29 × 105 at the 1 : 1 : 0.1 weight ratio of PU/ZnO/15W, which grew by 62% and 42% compared to pure PU, respectively. This work contributes to an understanding of the combined effect of ash and SOF on soot combustion.