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Two processes of high‐salinity water (≥34.7 psu; HSW) intrusion were recorded by an Argo float in the northeastern South China Sea (SCS) during fall‐winter of 2015/2016. Combined with the satellite altimetry and reanalysis data, the influence of related eddy pairs on HSW transport was investigated. The results show that apart from the Kuroshio‐originated anticyclonic eddy (AE), the localized cyclonic eddy (CE), and the westward jet between the eddy pair all contributed to the HSW transport. In the first process, the effect of eddy trapping accounted for 74% of the HSW transport, while the associated jet accounted for the residual 26%. The contribution of the southern CE was stronger than that of the northern AE. In the second process, the Kuroshio‐originated AE and its southern jet dominated the HSW transport. The westward jet conveyed abundant HSW to the interior SCS before the eddy pair propagated westward, accounting for 52% of HSW transport, while AE accounted for 43% and CE for 5%. Energy analysis showed that barotropic and baroclinic instabilities were important for the generation and growth of the AE in both processes, and CE in the first process was produced by baroclinic instability and wind stress work, while CE in the second process was predominantly triggered by barotropic instability. The development of eddy pairs combined with the SCS interior circulation jointly affected the HSW transport. This study identified the important contributions from two eddy pairs and discussed the effect of interior circulation‐Kuroshio interaction on HSW intrusion in the northern SCS. Plain Language Summary: In this study, we report a special case in which two successive anticyclonic eddies were shed from the Kuroshio into the South China Sea (SCS) during fall‐winter of 2015/2016. We focus on the high‐salinity water (HSW) intrusion induced by the eddy pair that includes the Kuroshio‐originated anticyclonic eddy and the localized cyclonic eddy. The eddies and their associated jet contribute to the transport of HSW from the western Pacific to the northern SCS. The relative contributions of eddy trapping and jet transport were related to the development of the eddy pair and the interior circulation in the SCS. Key Points: Two processes of eddy pair intrusion were revealed in the northeastern South China Sea during fall‐winter of 2015/2016The northern anticyclonic and southern cyclonic eddies, together with their associated jet, affected the high‐salinity water transportThe interior circulation and the development of eddy pairs jointly affected the relative contributions of eddy trapping and jet transport [ABSTRACT FROM AUTHOR]

Pulmonary vascular remodeling is the most important pathological characteristic of pulmonary arterial hypertension (PAH). No effective treatment for PAH is currently available because the mechanism underlying vascular remodeling is not completely clear. CD248, also known as endosialin, is a transmembrane protein that is highly expressed in pericytes and fibroblasts. Here, we evaluated the role of CD248 in pulmonary vascular remodeling and the processes of PAH pathogenesis. Activation of CD248 in pulmonary artery smooth muscle cells (PASMCs) was found to be proportional to the severity of PAH. CD248 contributed to platelet‐derived growth factor‐BB (PDGF‐BB)‐induced PASMC proliferation and migration along with the shift to more synthetic phenotypes. In contrast, treatment with Cd248 siRNA or the anti‐CD248 therapeutic antibody (ontuxizumab) significantly inhibited the PDGF signaling pathway, obstructed NF‐κB p65‐mediated transcription of Nox4, and decreased reactive oxygen species production induced by PDGF‐BB in PAMSCs. In addition, knockdown of CD248 alleviated pulmonary vascular remodeling in rat PAH models. This study provides novel insights into the dysfunction of PASMCs leading to pulmonary vascular remodeling, and provides evidence for anti‐remodeling treatment for PAH via the immediate targeting of CD248. [ABSTRACT FROM AUTHOR]

Highlights • Artificial inoculation of onion bulbs causes basal rot. • Pathogenic infection increases emission of volatile organic compounds. • Volatile organic compounds correlate positively with the extent of infection. • 1-Propanethiol, methyl propyl sulfide and styrene are markers of fungal infection. Abstract Diseases develop during the storage of onions. To minimize losses, new methods are needed to identify diseased bulbs early in storage. Volatile organic compounds (VOCs), the respiration rate, weight loss, and the dry matter content were investigated for 1–7 weeks post inoculation of bulbs with water (control) and two strains (Fox006 or Fox260) of Fusarium oxysporum f. sp. cepae. Photos, multispectral image analysis, and real-time polymerase chain reaction (PCR) showed no infection in the control onions, weak pathogenic infection in Fox006-onions, and strong pathogenic infection in Fox260-onions at week 7 post inoculation. Infected bulbs exhibited increased respiration rate, increased VOC emission rate, and increased weight loss. The control and Fox006-onions did not respond to inoculation and had similar reaction pattern. Forty-three different VOCs were measured, of which 17 compounds had sulfur in their chemical structure. 1-Propanethiol, methyl propyl sulfide, and styrene were emitted in high concentrations and were positively correlated with the extent of infection (r = 0.82 – 0.89). Therefore, these compounds were the most promising volatile markers of Fusarium basal rot infection. For the first time, we show that the extent of fungal infection determined by real-time PCR in onion bulbs is related with VOC emission. [ABSTRACT FROM AUTHOR]

A calibrated, coupled model of the Bohai and Yellow Seas is developed to investigate sediment transport and deposition processes around a distinct clinoform east of the Shandong Peninsula. On the clinoform, deposition patterns vary seasonally with the regional hydrography and the East Asian Monsoon. A local maximum in sediment deposition is located offshore from spring to autumn, whereas sediment deposition is greater near the coast and decreases seaward in winter. From spring to autumn, a thermal front develops around the Yellow Sea Cold Water Mass and limits sediment transport seaward, enhancing sediment deposition and leading to high deposition rate in a focused region offshore. Sediment is transported to the region by the southward basin-scale cyclonic circulation, and the cross-shelf gradient in stratification, sediment resuspension, and vertical mixing at the front lead to a convergence in sediment transport and deposition. Sediment deposition over the clinoform is the greatest during the transition from summer to autumn when the thermal front persists but sediment supply increases. This results from weakened stratification and greater resuspension near the coast due to stronger winds, waves, and sea-surface cooling. A seasonal seaward shift of the frontal position toward deeper water is consistent with the decreasing heat flux, and the corresponding shift in location of maximum sediment deposition shifts seaward. In winter, the thermocline disappears and vertical mixing increases throughout the region. SSC over the clinoform increases due to active resuspension and net deposition decreases, and instead sediment is transported seaward and deposits in the South Yellow Sea. Current velocity, SSC and sediment deposition rates decrease seaward, in contrast to the focused trapping at the thermal front from spring to autumn. The deposition rates around the thermal front from spring to autumn are greater than in the winter, so the high net sediment accumulation over an annual cycle occurs in the same region as the longer-term accumulation preserved in the omega-shaped clinoform. • Sediment deposition rates are increased at a thermal front from spring to autumn at east of the Shandong Peninsula. • Seasonal shifts of the position of thermal front and sediment depo-center broaden the sediment accumulation region. • The monsoonal climate plays a dominant role in the seasonally varying circulation and sediment transport in the Yellow Sea. [ABSTRACT FROM AUTHOR]

A long shelf life of onions (Allium cepa L.) is of high importance in the onion industry. Onions are dried and stored in large wooden boxes that are difficult to access. Monitoring temperature and relative humidity during these processes is challenging. Moreover, quality may change in storage without being noticed. Therefore, there is a need to find alternative methods for monitoring and controlling the drying and storage processes of onions and to identify early changes in quality during storage. The potential use of online measurements of temperature and relative humidity (RH) in the vicinity of onions was evaluated during drying and long-term storage of six onion batches (four cultivars and three selections of one of the cultivars) in commercial storage. The batches varied in bulb weight, dry matter content, firmness and disease incidence. The dry matter content and firmness decreased during storage, while the respiration rate and incidences of individual and total disease increased. Two of the batches had low storability with high disease incidences and high average temperatures and variations in the RH. The results showed that tracking the temperature and RH in the vicinity of the onions is a promising tool for improving the drying and storage processes in commercial storage and for identifying onion batches with reduced storability early in storage. [ABSTRACT FROM AUTHOR]

Abstract Basal rot is a common onion disease and is mainly caused by Fusarium oxysporum f. sp. cepae and Fusarium proliferatum. To study the possibility of using volatile organic compounds (VOCs) as biomarkers for these fungi, pathogenic isolates of F. oxysporum and F. proliferatum from onions were cultivated in onion medium and VOCs were measured by solid phase microextraction (SPME). Forty-two compounds were detected, and thirty of these compounds were highly related to fungal metabolic activity. Allyl mercaptan was specific to F. oxysporum isolate Fox006. Analysis of the VOCs showed significant differences between the two species and among different isolates within the same species. Sixteen of the VOCs showed were highly positively correlated with the fungal biomass estimated by real-time polymerase chain reaction (PCR). Ethanol, ethyl formate, ethyl acetate, 2-methyl-1-propanol, methyl thioacetate, n-propyl acetate and 3-methyl-1-butanol are volatile metabolites that were potential indicators of Fusarium growth on onions. Highlights • VOCs from onion-pathogenic Fusarium fungi were studied for the first time. • Specific VOCs were detected from F. oxysporum and F. proliferatum. • Fungal volatiles were quantitatively related with fungal biomass. • VOCs from F. oxysporum isolates correlated with their taxonomics. [ABSTRACT FROM AUTHOR]

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Obesity and cigarette smoke are major cardiovascular (CV) risk factors and, when coexisting in the same individuals, have additive/synergistic effects upon CVD. We studied the mechanisms involved in nicotine enhancement of CVD in Sprague Dawley rats with diet–induced obesity. The rats were fed either a high fat (HFD) or normal rat chow diet with or without nicotine (100 mg/L in drinking water) for 20 weeks. HFD rats developed central obesity, increased systolic blood pressure (SBP), aortic superoxide (O2-) production, and impaired endothelial nitric oxide synthase (eNOS) and endothelium-dependent relaxation to acetylcholine (EDR). Nicotine further increased SBP, O2- and impaired eNOS and EDR in obese rats. In the peritoneal macrophages from obese rats, tumor necrosis factor (TNF) α, interleukin 1β and CD36 were increased, and were further increased in nicotine-treated obese rats. Using PCR array we found that 3 of 84 target proinflammatory genes were increased by 2–4 fold in the aorta of obese rats, 11 of the target genes were further increased in nicotine-treated obese rats. HUVECs, incubated with conditioned medium from the peritoneal macrophages of nicotine treated-obese rats, exhibited reduced eNOS and increased NADPH oxidase subunits gp91phox and p22phox expression. Those effects were partially prevented by adding anti-TNFα antibody to the conditioned medium. Our results suggest that nicotine aggravates the CV effects of diet–induced obesity including the oxidative stress, vascular inflammation and endothelial dysfunction. The underlying mechanisms may involve in targeting endothelium by enhancement of macrophage-derived TNFα. [ABSTRACT FROM AUTHOR]

Puerarin is an isoflavonoid isolated from the Chinese herb, Kudzu roots (also known as Gegen), which has been widely used for the treatment of hypertensive diseases and diabetic mellitus in traditional Chinese medicine. Dahl salt-sensitive (DS) rat is a genetic model of salt-sensitive hypertension with cardiovascular injury and vascular insulin resistance. Here, we investigated whether puerarin improved vascular insulin resistance and attenuated cardiac and aortic remodeling in salt-sensitive hypertension. DS rats were given a normal (NS) or high salt diet (HS) for five weeks. An additional group of DS rats was pretreated with puerarin and NS for 10 days, then switched to HS plus puerarin for five weeks. HS for five weeks increased systolic blood pressure (SBP), cardiac hypertrophy and fibrosis, and aortic hypertrophy with increased the expression of phosphor-ERK1/2 in the aorta and heart; puerarin attenuated cardiac and aortic hypertrophy, cardiac fibrosis and phosphor-ERK1/2 with a mild reduction in SBP. Hypertensive rats also manifested impairment of acetylcholine- and insulin-mediated vasorelaxation and insulin-mediated Akt and eNOS phosphorylation associated with the activation of NFB/TNF/JNK pathway. Puerarin improved acetylcholine- and insulin-mediated vasorelaxation and insulin-stimulated Akt/NO signaling with the inhibition of the NFB inflammatory pathway. Our results demonstrated that in salt-sensitive hypertension, puerarin improved vascular insulin action with cardiovascular beneficial effects. Our results found that the underlying mechanisms may involve its inhibition of NFB/JNK and ERK1/2 pathway. These results suggest that puerarin could be used as a new antihypertensive agent to expand our armamentarium for the prevention and treatment of end-organ damage in individuals with hypertension and metabolic diseases. [ABSTRACT FROM AUTHOR]

Puerarin, a major isoflavonoid compound from Chinese herb Kudzu roots, has been widely used for the treatment of hypertensive and cardiovascular diseases in China. Here, we investigated puerarin’s beneficial effects on the cardiovascular system in angiotensin (Ang) II-induced hypertensive rats. Sprague–Dawley rats were treated with Ang II for 5 days or with puerarin for 10 days followed by Ang II and puerarin for 5 days. Endothelium-dependent relaxation (EDR) to acetylcholine was determined using an organ chamber bath. Ang II increased the systolic blood pressure (SBP: 178 ± 5 mmHg vs. 112 ± 3 mmHg in control,p< 0.05), aortic (30%,p< 0.05), and left ventricular (LV) weight (23%); puerarin reduced SBP (160 ± 2 mmHg,p< 0.05), aortic, and left ventricular weight in Ang II-infused rats. Puerarin also reduced aortic medial thickness and myocardial cell surface area in Ang II-infused rats. Compared with control rats, Ang II infused rats exhibited an impaired EDR with reduction in the protein expression of phosphor-eNOS at Ser 1177 and an increase in the expression of gp91phox (85%), p22phox (113%), transforming growth factor β1 (145%) and vascular cell adhesion molecule 1 (82%). Puerarin improved EDR and reversed the changes in Ang II-induced protein expression of above molecules. Our results demonstrate that in Ang II-induced hypertensive rats, puerarin protects against endothelial dysfunction and end organ damage with a mild reduction in SBP, and that the cardiovascular beneficial effects of puerarin may be in part attributed to its anti-oxidant and upregulation of phosphor-eNOS. [ABSTRACT FROM AUTHOR]

Distribution of suspended sediment in the Bohai Sea and its seasonal variability were investigated based on the datasets obtained from four cruises carried out in different seasons in 2010 and 2012. The results indicate that the spatial distribution of suspended sediment in the Bohai Sea was dominated by the river input and coastal resuspension that depends on the type of local surface sediment and hydrodynamics. The suspended sediment was mostly concentrated in the southern Bohai Sea particularly around the Yellow River Delta in the summer season as impacted by the river plume but confined within a very limited area near the river mouth, whereas in winter–spring seasons sediment concentration became much higher as a result of active coastal resuspension induced by energetic wave actions in the shallow water. High sediment concentration was found in Liaodong Bay in winter–spring seasons when dynamics become strong but decrease significantly in summer seasons. The sediment concentration in the southern Bohai Strait was much higher than that in the northern part, suggesting evident sediment export to the Yellow Sea particularly in the winter–spring seasons. Strong seasonal variability of suspended sediment distribution in the Bohai Sea was consistent with the monsoon activity and associated wave actions and coastal currents that are varying seasonally. The dominance of seasonal monsoon signal and associated wave dynamics make the subaqueous Yellow River delta to be a major sink for the terrestrial sediment in the summer seasons, but transiting to a primary source in winter–spring seasons for sediment redistribution in the Bohai Sea and sediment export to the Yellow Sea. The seasonal patterns of suspended sediment distribution in the Bohai Sea and the dominance of monsoon activities may provide a good reference to understanding the sediment transport in the China Shelf Seas where sediment resuspension and coastal circulation are evidently driven by monsoon. [ABSTRACT FROM AUTHOR]

A novel and simple process for the preparative extraction, separation, and purification of high-purity (–)-borneol and xanthoxylin, synchronously, from the leaves ofBlumea balsamifera(L.) DC was developed. Simultaneous distillation and extraction, silica gel column chromatography, and recrystallization were applied to the preparation. Two objective compounds with the purity of 98% were obtained, and the losses were minimal during the whole procedure. It is the first time that the preparation of high-purity (–)-borneol and xanthoxylin at the same time were achieved. [ABSTRACT FROM AUTHOR]

• Fe was highly dispersed on MIL-100(Fe) derived porous carbon with a high loading (>37 wt%). • XRD and HRTEM show particle size decrease for Na, Cu, and Ru-promoted catalysts. • Cu-promoted catalysts show a high CO conversion and a stable FT activity. • Na addition increased O/P ratio and C 5+ selectivity in product distribution. • Ru-promoted catalysts show a deactivation at high reaction temperature (340 °C). Fischer-Tropsch synthesis (FTS) is studied over Metal-organic framework (MOF) based porous carbon supported iron catalysts promoted with Na, Cu and Ru metals. The FTS results showed that all promoters can enhance CO conversion, FT product yield (FTY), and CO 2 selectivity is also increased. Among all promoters, Cu-based sample exhibits the best promoting effect in activity (FTY=0.154 mol CO g Fe −1 h −1). Interestingly, the activity is about 2 times higher to that of unpromoted catalysts. Ru-contained sample exhibits the most significant influence on the light hydrocarbon production, with the C 1–4 hydrocarbon selectivity above 70%. Na-contained sample performed the highest C 5+ selectivity of 66% with a medium CO conversion of 51%. The improved FTS activity and selectivity of promoted catalysts is related to the decrease in iron particle size as confirmed by X-ray diffraction (XRD), and transmission electron microscopy (TEM). It is confirmed, the small iron particles of the promoted catalyst are stabilized on the surface of carbon matrix, preventing further aggregation at high temperature, which is contributed to the improved FTS performance. Our research study showed that Na, Cu and Ru can not only affect the distribution of resulting products but also improve the activity of FTS. In short, the effect of Cu is remarkable on the MOF-derived catalyst. Similarly, the MOF-derived porous carbon catalysts confined the iron species during the reaction process, provide a clear structure-activity relationship between the promoters and the catalytic performance. Finally, this novel work can provide a new pathway for metal-organic framework-derived Fe-embedded porous carbon catalysts for Fischer-Tropsch synthesis. [Display omitted] [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a common malignant tumor that primarily affects the elderly population. Surgery is one of the main treatment modalities for CRC. Frailty is a prevalent characteristic among the elderly and a leading cause of mortality. The frailty index (FI) is a comprehensive tool for assessing patients' frailty status, quantifying indicators such as weight loss, fatigue, and nutritional status, to reflect the degree of frailty. In recent years, the FI has undergone modifications to more accurately evaluate the risk of surgical complications and prognosis in CRC patients. This review summarizes the methods for frailty assessment, the development and modifications of the FI, and compiles the research findings and applications of the FI in predicting surgical complications, postoperative recovery, and survival rates in CRC patients. Furthermore, limitations in the current modified frailty index (mFI) and future research directions are discussed. This review provides essential references for further understanding the role of frailty in CRC patients and the clinical application of the mFI. [ABSTRACT FROM AUTHOR]

MiR-328–3p has been reported to be downregulated and serve as a tumor suppressor in several cancers. Previous studies only have reported the downregulation of miR-328–3p in CRC. However, the roles of miR-328–3p in CRC growth and metastasis were unknown. In this study, we demonstrated that miR-328–3p overexpression inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). The PI3K/Akt signaling pathway was also inactivated by miR-328–3p overexpression. MiR-328–3p knockdown showed the opposite effects. In addition, we confirmed that miR-328–3p directly bound to 3′UTR of Girdin and negatively regulated its expression. Girdin knockdown or treatment with PI3K inhibitor LY294002 blocked the effects of miR-328–3p inhibitor on cell proliferation, metastasis, and the PI3K/Akt signaling pathway. Moreover, pre-miR-328 decreased numbers of liver metastatic nodules, and reduced the levels of p-Akt, p-Girdin, and Girdin in metastatic tissues in liver. In conclusion, miR-328–3p may inhibit proliferation and metastasis of CRC cells by targeting Girdin and inactivating the PI3K/Akt signaling pathway. MiR-328–3p may be a novel target in cancer therapy. • MiR-328–3p inhibited cell proliferation and metastasis via Girdin and the PI3K/Akt pathway. • MiR-328–3p knockdown showed the opposite effects. • Girdin is a direct target of miR-328–3p. • Pre-miR-328 suppressed CRC liver metastasis in vivo. [ABSTRACT FROM AUTHOR]

MiR-346-5p is overexpressed in several cancers, including colorectal cancer (CRC). However, the effects of miR-346-5p on CRC progression have not yet been clarified. In our study, miR-346-5p levels in four CRC cell lines and normal human colon epithelial cells were determined by real-time PCR. SW620 and HCT116 cells were selected and then transfected with miR-346-5p mimic, miR-346-5p inhibitor, or specific siRNAs targeting F-box/LRR-repeat protein 2 (FBXL2). Cell proliferation, cell cycle distribution and cell cycle regulators were examined by CCK-8 assay, flow cytometry, and western blot. The binding of miR-346-5p on 3′ untranslated region (UTR) of FBXL2 were verified by dual-luciferase reporter assay. CRC cells were co-transfected with miR-346-5p inhibitor and siFBXL2 to investigate the involvement of FBXL2. Interaction of FBXL2 with forkhead box M1 (FoxM1) was examined by co-immunoprecipitation (Co-IP) assay. The effect of miR-346-5p knockdown on CRC tumorigenesis in vivo was investigated. Here, we found that miR-346-5p overexpression promoted, while miR-346-5p knockdown inhibited cell proliferation and G1-S transition. Inhibition of FBXL2 showed similar effects as miR-346-5p overexpression. Moreover, we verified that FBXL2 was a direct target of miR-346-5p. FBXL2 interacted with FoxM1, and then negatively regulated both FoxM1 and nuclear β-catenin levels. Additionally, FBXL2 knockdown reversed the effects of miR-346-5p inhibitor. In xenograft models, miR-346-5p knockdown significantly inhibited tumor growth, increased FBXL2 expression, and downregulated the levels of FoxM1 and nuclear β-catenin. In conclusion, miR-346-5p may promote CRC growth by targeting FBXL2 and activating the β-catenin signaling pathway. MiR-346-5p may be a novel target in cancer therapy. Unlabelled Image • MiR-346-5p overexpression promoted, while miR-346-5p knockdown inhibited cell proliferation and G1-S transition in vitro. • FBXL2 knockdown showed similar effects as miR-346-5p overexpression on cell proliferation and cell cycle distribution. • FBXL2 interacted with FoxM1, and then negatively regulated both FoxM1 and nuclear β-catenin levels • MiR-346-5p knockdown significantly inhibited tumor growth in vivo. • MiR-346-5p may promote CRC growth by targeting FBXL2 and activating the β-catenin signaling pathway [ABSTRACT FROM AUTHOR]

Background: Lenvatinib is in a first-line therapy for advanced hepatocellular carcinoma (HCC). However, drug resistance is one of the principal obstacles for treatment failure. The molecular mechanism of Lenvatinib resistance has not been well investigated. Materials and methods: A genome-wide CRISPR/Cas9 knockout screening system was established and bioinformatic analysis was used to identify critical genes associated with Lenvatinib resistance. Cell proliferation assays, colony formation assays and cell migration assays were performed to investigate the effect of drug resistance associated genes, particularly DUSP4, on cancer cell malignant behavior during Lenvatinib treatment. In vivo experiments were conducted by using a xenograft mouse model. Results: We identified six genes that were associated with Lenvatinib resistance in HCC, including DUSP4, CCBL1, DHDH, CNTN2, NOS3 and TNF. DUSP4 was found to be significantly decreased at the mRNA and protein levels in Lenvatinib resistant HCC cells. DUSP4 knockout enhanced HCC cell survival, cell proliferation and migration during Lenvatinib treatment in vitro and in vivo , accompanied by regulation of p-ERK and p-MEK levels. This finding implied that DUSP4 deficiency induced Lenvatinib resistance. Interestingly, DUSP4 deficiency induced Lenvatinib resistance was abrogated by the MEK inhibitor Selumetinib, implying that MEK phosphorylation and DUSP4-inhibition dependent ERK activation were required for drug resistance. Finally, we found that DUSP4 deficiency was associated with HCC prognosis and response to Lenvatinib based on clinical data. Conclusions: DUSP4 deficiency mediates Lenvatinib resistance by activating MAPK/ERK signaling and combination therapy using Lenvatinib and MEK inhibitors may be a promising therapeutic strategy for overcoming Lenvatinib resistance., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Remote ischemic perconditioning (RIPerC) could improve neuronal damage and inhibit inflammation and apoptosis. We conducted an in-depth exploration of the protective mechanism of RIPerC in cerebral ischaemia injury. In this study, a middle cerebral artery occlusion (MCAO) mouse model was built. According to whether to undergo RIPerC treatment and the duration of cerebral infarction, mice were divided into 5 groups: Sham group, MCAO 3.0 h group, MCAO 4.5 h group, MCAO 3.0 h + RIPerC group, and MCAO 4.5 h + RIPerC group. Overexpressed or silenced miR-153-5p was transfected into the cells to analyse the effects of oxygen-glucose deprivation (OGD) treatment on Neuro-2a cell viability, apoptosis, and related gene expressions by performing quantitative real-time polymerase chain reaction (qRT-PCR), MTT assay, flow cytometry, and Western blot. Bioinformatics analysis, qRT-PCR, dual-luciferase experiment, and RNA immunoprecipitation (RIP) were used to screen and verify the miRNA and downstream mRNA-targeted Toll-like receptor 4 (TLR4). The rescue test further verified the effects of the above target genes and miR-153-5p on the apoptosis of OGD-injured cells, apoptosis-related proteins, and the p65/IkBa pathway. The plasma levels of miR-153-5p in 68 patients with ischaemic stroke were detected within 6 hours of onset, and the patients were followed up for 3 months. We found that, in in vivo studies, RIPerC treatment inhibits cerebral infarction volume and neurological damage, and promotes the expression of miR-153-5p in the MCAO animal model. The expression of miR-153-5p in OGD cells was inhibited, and its upregulation protected Neuro-2a cells. TLR4 was predicted to be the target gene of miR-153-5p and could offset the effect of miR-153-5p mimic on OGD cell protection after up-regulating TLR4. TLR4 overexpression promoted the activation of OGD on the p65/IkBa pathway. Compared with the high plasma miR-153-5p group, the 3-month overall survival rate of patients with ischaemic stroke in the low plasma miR-153-5p group was significantly lower (c2 = 5.095, p = 0.024). In conclusion, RIPerC intervention inhibits the damage caused by cerebral ischaemia partially through the miR-153-5p/TLR4/p65/IkBa signalling pathway.

Cisplatin (CDDP) is widely used in clinical settings for the treatment of various cancers. However, ototoxicity is a major side effect of CDDP, and there is an associated risk of irreversible hearing loss. We previously demonstrated that CDDP could induce ototoxicity via activation of the transient receptor potential vanilloid receptor 1 (TRPV1) pathway and subsequent induction of oxidative stress. The present study investigated whether ursolic acid (UA) treatment could protect against CDDP‑induced ototoxicity. UA is a triterpenoid with strong antioxidant activity widely used in China for the treatment of liver diseases. This traditional Chinese medicine is mainly isolated from bearberry, a Chinese herb. The present results showed that CDDP increased auditory brainstem response threshold shifts in frequencies associated with observed damage to the outer hair cells. Moreover, CDDP increased the expression of TRPV1, calpain 2 and caspase‑3 in the cochlea, and the levels of Ca2+ and 4‑hydroxynonenal. UA co‑treatment significantly attenuated CDDP‑induced hearing loss and inhibited TRPV1 pathway activation. In addition, UA enhanced CDDP‑induced growth inhibition in the human ovarian cancer cell line SKOV3, suggesting that UA synergizes with CDDP in vitro. Collectively, the present data suggested that UA could effectively attenuate CDDP‑induced hearing loss by inhibiting the TRPV1/Ca²+/calpain‑oxidative stress pathway without impairing the antitumor effects of CDDP.

Objective: To investigate the role of Eclipta prostrata (E. prostrata) extract in improving spatial learning and memory deficits in D-galactose-induced aging in rats., Methods: Rats were divided into five groups, with 10 animals in each group. Aging rats were produced by treatment with 100 mg·kg-1·d-1 of D-galactose for 6 weeks. Rats in the E. prostrata treatment groups received an aqueous extract of E. prostrata orally at a concentration of 50, 100, or 200 mg·kg-1·d-1 for 3 weeks. Animals in both the normal and model groups were treated with similar volumes of saline. Spatial memory performance was measured using the Morris water maze. The mRNA levels and enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were analyzed using real-time quantitative PCR and spectrophotometry, respectively. The levels of induced nitric oxide synthase (iNOS), nitric oxide (NO), dopamine (DA), norepinephrine (NE), and serotonin (5-HT) were determined using enzyme-linked immunosorbent assay and spectrophotometry., Results: Compared with the normal group, rats in the D-galactose-treated model group exhibited significant memory loss. There was severe damage to the hippocampal CA1 area, and expression levels of SOD, CAT, GPx, and GR were significantly decreased in the model group compared with the normal group. In the model group, levels of iNOS and NO were significantly increased compared with the normal group. However, treatment with E. prostrata extract reversed the conditions caused by D-galactose-induced aging, especially in the groups with higher treatment concentrations. Compared with the normal group, the levels of DA, NE, and 5-HT were significantly lower in the D-galactose-treated model group. In the E. prostrata extract-treated groups, however, there was a dose-dependent upregulation of DA, NE, and 5-HT expression., Conclusion: Our results suggest that administration of E. prostrata extract can result in an improvement in the learning and memory impairments that are induced by D-galactose treatment in rats. This improvement may be the result of enhanced antioxidative ability, decreased iNOS and NO levels, and the induction of DA, NE, and 5-HT expression in the brain.

Background: The modified early warning score (MEWS) was set up to supply prompt recognition of clinically deteriorating patients before they undergo a severe and life-threatening event. The study aimed to describe the probable usefulness of the MEWS in identifying deteriorating post-Whipple patients in hospital wards., Methods: We performed a study to analyze the relationship between the vital parameters and postoperative severe adverse events of patients after Whipple surgery in Guangdong Provincial People's Hospital from 2000 to 2017. In the retrospective study, a total of 13,651 sets of vital parameters in 236 Whipple postoperative patients were included. Subsequently, we applied a MEWS scoring system and explored the accuracy of the MEWS in evaluating the patients' final events versus advanced mathematical models. We then put the MEWS into the ward warning system and confirmed the accuracy of the MEWS based on the results of prospective studies again., Results: We assessed the ability of the MEWS to predict postoperative complications with an accuracy rate of 90.86-91.23%, a sensitivity of 83.04-90.88%, and a specificity of 90.85-95.73%., Conclusions: The MEWS model was applied to identify post-Whipple patients at risk of complication. Once the MEWS ≥2, interventions were needed to minimize the adverse events. Our data suggest that the MEWS is comparable to the advanced mathematical models, but MEWS is more accessible to perform and more generally applicable., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Annals of Translational Medicine. All rights reserved.)

[This corrects the article DOI: 10.3389/fphar.2018.01226.].