Search

• GM1 attenuates neurological dysfunction in ischemic stroke rats. • The neuroprotective effect of GM1 is related to SPTBN1-mediated signaling. • SPTBN1 may be a potential target in ischemic stroke and related diseases. Monosialoganglioside GM1 (GM1) has long been used as a therapeutic agent for neurological diseases in the clinical treatment of ischemic stroke. However, the mechanism underlying the neuroprotective function of GM1 is still obscure until now. In this study, we investigated the effects of GM1 in ischemia and reperfusion (I/R) brain injury models. Middle cerebral artery occlusion and reperfusion (MCAO/R) rats were treated with GM1 (60 mg·kg−1·d−1, tail vein injection) for 2 weeks. The results showed that GM1 substantially attenuated the MCAO/R-induced neurological dysfunction and inhibited the inflammatory responses and cell apoptosis in ischemic parietal cortex. We further revealed that GM1 inhibited the activation of NFκB/MAPK signaling pathway induced by MCAO/R injury. To explore its underlying mechanism of the neuroprotective effect, transcriptome sequencing was introduced to screen the differentially expressed genes (DEGs). By function enrichment and PPI network analyses, Sptbn1 was identified as a node gene in the network regulated by GM1 treatment. In the MCAO/R model of rats and oxygen-glucose deprivation and reperfusion (OGD/R) model of primary culture of rat cortical neurons, we first found that SPTBN1 was involved in the attenuation of I/R induced neuronal injury after GM1 administration. In SPTBN1 -knockdown SH-SY5Y cells, the treatment with GM1 (20 μM) significantly increased SPTBN1 level. Moreover, OGD/R decreased SPTBN1 level in SPTBN1 -overexpressed SH-SY5Y cells. These results indicated that GM1 might achieve its potent neuroprotective effects by regulating inflammatory response, cell apoptosis, and cytomembrane and cytoskeleton signals through SPTBN1. Therefore, SPTBN1 may be a potential target for the treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Acute graft-versus-host disease (aGVHD), which is mainly mediated by allogeneic T cells, is a decisive factor in the success of allogeneic hematopoietic stem cell transplantation (allo-HCT). Prophylaxis for aGVHD in clinical patients is unsatisfactory, and there is still a huge unmet need for novel approaches. Icariin (ICA) shows potent anti-inflammatory activity and suppresses T cell-mediated immune responses. Thus, ICA is a potential drug for the prevention of aGVHD. However, there is no data assessing the impact of ICA on aGVHD after allo-HCT. This study aimed to investigate the protective effect of ICA against aGVHD and its mechanisms. Moreover, the impact of ICA on the graft-versus-leukemia (GVL) effect and engraftment of donor hematopoietic and immune cells were assessed. Different murine models of allo-HCT were developed to study the influence of the ICA on GVHD and GVL effect. Flow cytometry was used to analyze the growth of leukemia cells, alterations in different immune cells, and apoptosis. Cell proliferation was determined using a CCK-8 assay. RNA sequencing and quantitative proteomic analysis were performed to elucidate the underlying mechanisms, which were further verified by polymerase chain reaction or functional experiments. Different concentrations of ICA exhibited opposite effects: low-concentration ICA promoted, while high concentrations suppressed the proliferation and function of T cells. A high dose of ICA administration during days +3 to +5 post-allo-HCT can alleviate murine aGVHD but does not affect the course of chronic GVHD (cGVHD), the GVL effect against both acute myeloid and lymphoblastic leukemia, or the recovery of donor hematological and immune cells. ICA extensively represses the expansion, function, and infiltration of donor alloreactive T cells, while preserving regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC). Quantitative proteomic analysis showed that downregulation of integrin-linked kinase (ILK) and lymphocyte cytosolic protein 2 (LCP2) expression was possibly associated with ICA-mediated aGVHD protective effects. Furthermore, an inhibitor of ILK, which can alleviate murine aGVHD administered early after allo-HCT. These findings suggest that the bioactivities of ICA are associated with its concentration and that ICA can effectively mitigate aGVHD without losing GVL activity or engraftment of donor hematopoietic and immune cells. Thus, ICA may be a promising drug for preventing aGVHD in clinical settings. ICA could alleviate murine acute GVHD via inhibiting the expansion and function of donor T cells, and their infiltration into aGVHD target organs post allo-HCT, while preserves regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC). Furthermore, ICA down-regulates proinflammatory cytokine in serum of recipient mice and costimulatory molecule expression on recipient B cells. [Display omitted] [ABSTRACT FROM AUTHOR]

Global warming has a profound effect on aquaculture. Salmon aquaculture, as an emerging industry in China, is particularly vulnerable to climate change. For this reason, spatial planning with mechanistic understanding is essential for mitigating and adapting to the impacts of climate change. Through the use of dynamic energy budget models for Atlantic salmon (Salmo salar) with fine-scale environmental data under 0 m, 20 m, 40 m, and 60 m depth, this study established a framework for identifying optimal regions for salmon aquaculture in the Yellow Sea under current and two Shared Socioeconomic Pathway scenarios (SSP1-2.6 and SSP5-8.5) in the 2050s. These results suggest that most regions in the Yellow Sea under 40 m and 60 m depth are suitable for salmon farming at both current and future scenarios, the central region of the Yellow Sea under 20 m (38°N, 123°E) is the optimal site for salmon aquaculture in China. Overall, these findings provide valuable support for aquaculture management and can help stakeholders create an effective blueprint for adaptation strategies. • Atlantic salmon aquaculture is feasible in the Yellow Sea. • The center of the Yellow Sea is deemed to be a optimal region for the offshore salmon industry. • Consideration of mesoscale environmental heterogeneity can improve the potential of offshore aquaculture. • Effective efforts by stakeholders are urgent for the sustainable development of salmon aquaculture in China. [ABSTRACT FROM AUTHOR]

H19 long non-coding RNA (lncRNA) has many functions in cancer. Some studies have reported that H19 acts as an oncogene and is involved in cancer progression by activating epithelial-mesenchymal transition (EMT), the cell cycle and angiogenesis via mechanisms like microRNA (miRNA) sponging - the binding to and inhibition of miRNA activity. This makes H19 lncRNA a potential target for cancer therapeutics. However, several conflicting studies have also found that H19 suppresses tumour development. In this review, we shed light on the possible reasons for these conflicting findings. We also summarise the current literature on the applications of H19 lncRNA in cancer therapy in many cancers and explore new avenues for future research. This includes the use of H19 in recombinant vectors, chemoresistance, epigenetic regulation, tumour microenvironment alteration and cancer immunotherapy. The relationship between H19 and the master tumour suppressor gene p53 is also explored. In most studies, H19 knockdown via RNA interference (RNAi) or epigenetic silencing inhibits cancer development. Thus, H19 lncRNA could be a promising target for the development of cancer therapeutics. This warrants further investigations into its translational research to improve cancer therapy outcomes. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases, such as hypertension and cardiac failure, have become the most major and global cause for threatening human health in recent years. Uncaria rhynchophylla as a traditional Chinese medicine is widely used to treat hypertension for a long history, whereas its medicinal effective components and potential action mechanism are uncertain. Therefore, twenty-four alkaloids (1–24) isolated from U. rhynchophylla were assayed for their relaxant effects against phenylephrine (Phe)-induced contraction of rat mesenteric arteries. Among them, we surprisingly found that uncarialin A (21) exhibited most potent relaxation effect against Phe-induced contraction (IC 50 = 0.18 μM) in the manner of independent on endothelium-derived vasorelaxing factors and endothelium. All the experiments including measurement of Ca2+ in vascular smooth muscle cells (VSMCs) by fluorescence microscopy, whole-cell path clamp, molecular docking, and molecular dynamics, demonstrated that uncarialin A (21) could significantly inhibit L-type calcium channel subunit alpha-1C (Cav1.2) via the hydrogen bond interaction with amino acid residue Met1186, allowing the inhibition of Ca2+ inward current. Our results suggested that uncarialin A (21) could be served as a potential L-type Cav1.2 blocker in the effective treatment of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • RRP effectively decreased oxidative stress in Aβ 1-42 -induced HT22 cells. • RRP successfully curtailed apoptosis of HT22 cells induced by Aβ 1-42. • RRP enhanced the resistance of nematodes to the external environment. • RRP ameliorated AD-like pathological phenotypes and inhibits Aβ aggregation in C. elegans. • RRP mitigated oxidative stress and apoptosis induced by PQ in nematodes. • The protective effect of RRP against oxidative stress appears to involve the activation of the Nrf2/SKN-1-ARE pathway. Alzheimer's disease (AD) is an age-related neurodegenerative disease, which manifests primarily as memory impairment accompanied by a gradual decline in cognitive function. Rehmanniae Radix Praeparata (RRP) is a traditional Chinese medicine herb, which is widely used clinically and has diverse pharmacological properties. However, the protective properties and the underlying mechanisms by which RRP counteracts oxidative stress to treat AD have not been elucidated. In the study, we explored the neuroprotective impact of RRP on mitigating oxidative stress damage using C. elegans and Aβ 1-42 -induced HT22 cells. In the study encompassing the use of HT22 cells, we detected cell viability, ROS level, MDA/T-AOC/CAT/SOD activity, HT22 cells apoptosis and Nrf2 translocation. Western blot analysis was used to examine changes in protein expression levels. In nematode experiments, we performed spawning assay, life-span assay, ROS level, MDA/T-AOC/CAT/SOD activity, chemotaxis assay, paralysis, serotonin sensitivity, Th S Staining, acridine orange assay, SKN-1 nuclear localization and the gst-4 expression. Pretreatment of RRP significantly reduced the generation of ROS and MDA in Aβ 1-42 -induced HT22 cells, and increase the T-AOC, CAT and total SOD activity. RRP mitigated the toxic effect and apoptosis induced by Aβ 1-42 treatment, as evident by reduced cytochrome C release and decreased ratio of cleaved caspase-9/caspase-9, BAX/Bcl-2 and cleaved caspase-3/caspase-3. Additionally, RRP was found to induce Nrf2 nuclear translocation, elevate the expression of Nrf2 protein in the nucleus, and promote the expression of NQO1 and HO-1 proteins. In terms of the nematode experiments, RRP could prolong the survival time of N2 nematodes and improve the resistance of nematodes to external stress. RRP improved chemotaxis to chemical substances and decreased the sensitivity to 5-HT was observed in the CL2355 nematodes. It also alleviated the paralysis process and reduce Aβ deposition in the pharynx of the CL4176 nematodes. RRP inhibited the production of ROS and MDA, and increased the activity of T-AOC, CAT and total SOD in the nematodes. RRP decreased apoptosis in N2 C. elegans. Together, the data demonstrated that RRP possesses antioxidant capacity by promoting SKN-1 nuclear translocation and GST-4 expression in C. elegans. Overall, our study suggested that the antioxidant effect of RRP might occur by regulation of Nrf2/ARE pathway in HT22 cells, and is relevant to the activation of SKN-1 in C. elegans. [ABSTRACT FROM AUTHOR]

The neutron star-neutron star and neutron star-black hole mergers may cause the intense radiation of high-frequency gravitational waves (GWs), they can also produce various electromagnetic emissions by ejecting materials outwards. Therefore, these merger events are the most important targets of current multi-messenger astronomical studies. The thermal transient radiation emitted from merger ejecta is called the kilonova or, more generally, the mergernova, which is powered by the radioactive decays of r-process elements, and the energy injection from the central merger product. This phenomenon was first predicted theoretically by Li and Paczynski in 1998, and confirmed by the optical-infrared observations of the GW170817 event in 2017. As a result, the kilonova/mergernova observation had played a crucial role in locating GW170817, identifying its astrophysical origin, and even constraining the nature of the merger product of this event. This paper briefly reviews the primary progress of kilonova/mergernova researches, including the initiative, improvement, and development of the model, the observational discoveries of candidates, and the optical electromagnetic counterpart of GW170817. [ABSTRACT FROM AUTHOR]

Abstract In the present study, Ti-27Nb alloy specimens were prepared from Ti/TiH 2 powders using Nb powders through the argon sintering process (ASP) and hydrogen sintering process (HSP). X-ray diffraction and scanning electron microscopy studies were conducted, and the sintered density, Vickers hardness, and Rockwell hardness of the Ti-27Nb alloys produced by different sintering processes, as a function of the vacuum sintering temperature (1350–1450 °C), were measured. The results showed that the Ti-27Nb alloy sintered bodies with the highest density and hardness were obtained by HSP. In addition, the pore size and number of HSP specimens were smaller and less than those of the ASP specimens. It was found that the Ti-27Nb alloy, produced by HSP, can prevent the formation of oxide layers, resulting in enhanced densification and hardness. Furthermore, HSP can also prevent the formation of hydrides and eliminate the dehydrogenation step. At the same time, the problem of brittleness and failure caused by hydride formation could be solved. Graphical abstract Unlabelled Image Highlights • A newly hydrogen sintering process (HSP) was developed for Ti-27Nb sintering. • Effects of HSP on the sintering properties of Ti-27Nb alloys were investigated. • HSP enhanced densification and hardness of Ti-27Nb sintered bodies. • HSP can prevent the formation of oxide layers and hydrides during sintering. [ABSTRACT FROM AUTHOR]

The sine and cosine transforms implemented with digital filters have been used in the Transient electromagnetic methods for a few decades. Kong (2007) proposed a method of obtaining filter coefficients, which are computed in the sample domain by Hankel transform pair. However, the curve shape of Hankel transform pair changes with a parameter, which usually is set to be 1 or 3 in the process of obtaining the digital filter coefficients of sine and cosine transforms. First, this study investigates the influence of the parameter on the digital filter algorithm of sine and cosine transforms based on the digital filter algorithm of Hankel transform and the relationship between the sine, cosine function and the ±1/2 order Bessel function of the first kind. The results show that the selection of the parameter highly influences the precision of digital filter algorithm. Second, upon the optimal selection of the parameter, it is found that an optimal sampling interval s also exists to achieve the best precision of digital filter algorithm. Finally, this study proposes four groups of sine and cosine transform digital filter coefficients with different length, which may help to develop the digital filter algorithm of sine and cosine transforms, and promote its application. [ABSTRACT FROM AUTHOR]

Phthalate has been widely used as a type of plasticiser in various consuming products in daily life. Recent studies have suggested that prenatal phthalate exposure may have adverse effects on fetal development. We aimed to identify the effects of in utero phthalate exposure on birth weight (BW). We evaluated a birth cohort comprising 3474 pregnant women and their single infants; 3103, 2975 and 2838 urine samples were collected in the first, second and third trimesters, respectively. Phthalate metabolites included monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEHHP), and mono-(2-ethyl-5-hydroxylhexyl) phthalate (MEOHP), which were analysed in the urine by using high performance liquid chromatography–tandem mass spectrometry. Mixed linear model was used in the statistical analysis. Generally, MMP and MEP exposure during pregnancy was associated with decreased birth weight of infants (MMP, β = − 12.192, p = 0.009; MEP, β = − 11.876, p = 0.014). Hierarchical analysis found that MMP and MEOHP exposure was associated with decreased infants' birth weight only in low birth weight groups (MMP, β = − 42.538, p = 0.005; MEOHP, β = − 63.224, p = 0.008); MEHP and MEHHP exposure was associated with decreased infants' birth weight in both low birth weight group (MEHP, β = − 42.348, p = 0.035; MEHHP, β = − 50.485, p = 0.006) and high birth weight group (MEHP, β = − 16.580, p = 0.034; MEHHP, β = − 18.009, p = 0.040), MBP and MEHP exposure were associated with increased infants' birth weight in male NBW group (MBP, β = 10.438, p = 0.039; MEHP, β = 13.223, p = 0.017). Moreover, the effect has sex difference. The reduction of birth weight associated with MEHP and MEOHP exposure was stronger in male infants, while MMP and MEP exposure was more significant in female infants. [ABSTRACT FROM AUTHOR]

A prospective cohort study of a Chinese population of mother–neonate pairs (n = 3103) was conducted to investigate the relationship between the cumulative hazard index (HI) of combined diethyl phthalate (DEP), dibutyl phthalate (DBP), dibenzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) exposure and birth outcomes. The estimated HI for phthalates was based on phthalate metabolite concentrations in urine collected between 5th and 14th gestational weeks. The median HI values according to the European Food Safety Authority tolerable daily intake (HI TDI ) and U.S. Environmental Protection Agency reference dose (HI RfD ) were 0.358 and 0.187, respectively. A total of 16.3% and 1.9% of the women exhibited HI TDI and HI RfD exceeding the value of one, respectively. In unadjusted models, the categories (low < P 25 , median P 25 –P 50 , high > P 75 ) of HI TDI were associated with decreased birth weight ( β = −26.34 g, p = 0.021) and head circumference ( β = −0.09 cm, p = 0.029), whereas those for HI RfD were negatively associated with birth weight ( β = −31.74 g, p = 0.005), birth length ( β = −0.11 cm, p = 0.032), head circumference ( β = −0.13 cm, p = 0.003) and chest circumference ( β = −0.10 cm, p = 0.021) in all neonates. Adjustment for potential confounders revealed that HI RfD was inversely associated with head circumference ( β = −0.10 cm, p = 0.020). Stratification by gender indicated that HI RfD was associated with decreased birth length ( β = −0.17 cm, p = 0.041) in infant boys and HI TDI was associated with decreased birth weight ( β = −33.12 g, p = 0.036) and head circumference ( β = −0.13 cm, p = 0.027) in girls. This is the first study on the cumulative risk assessment of phthalate exposures in pregnant Chinese women. We found that the HI values of multiple phthalate co-exposure were sex-specifically related to birth outcomes. [ABSTRACT FROM AUTHOR]

• A novel meroterpenoid with an unique 6/8/9/4-tetracyclic nucleus was isolated. • The absolute configuration was confirmed by computational 13C NMR and optical rotation data. • Compound 1 exhibited potential cytotoxic activities. Littordial F (1), a novel meroterpenoid with an unique 6/8/9/4-tetracyclic nucleus, was isolated from the leaves of Psidium littorale. The structure of 1 was established by spectroscopic data, and its absolute configuration was confirmed by computational 13C NMR and optical rotation data. Compound 1 exhibited potential cytotoxic activities on A549, B16, and HepG-2 cell lines. A plausible biosynthetic pathway for littordial F was proposed. [ABSTRACT FROM AUTHOR]