Search

Sepsis is considered as a severe illness due to its high mortality. Sepsis can cause septic encephalopathy, thus leading to brain injury, behavioral and cognitive dysfunction. Pyroptosis is a type of regulated cell death (RCD) and takes a crucial part in occurrence and development of sepsis. Americanin B (AMEB) is a lignan compounds, which is extracted from Vernicia fordii. In our previous study, AMEB could inhibit microglial activation in inflammatory cell model. However, the function of AMEB in septic encephalopathy mice is uncertain. It would be worthwhile to ascertain the role and mechanism of AMEB in sepsis. Current study designs to certify the relationship between pyroptosis and septic encephalopathy, and investigate whether AMEB can restrain NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation and restrict pyroptosis by targeting NLRP3 in septic mice model. C57BL/6 mice were utilized to perform sepsis model in vivo experiments. BV-2 cell lines were used for in vitro experiments. In vivo sepsis model was established by lipopolysaccharide (LPS) intraperitoneal injection in male C57BL/6 J mice and in vitro model was exposed by LPS plus ATP in BV-2 cells. The survival rate was monitored on the corresponding days. NLRP3, apoptosis associated Speck-like protein (ASC), caspase-1, GasderminD (GSDMD), interleukin-1β (IL-1β) and interleukin-18 (IL-18) level were detected by western blotting and immunofluorescence analysis. Molecular docking, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) experiments, RNAi transfection and quantitative real-time PCR were applied to confirm the potential target of AMEB. The results suggested that AMEB could rise survival percentage and lighten brain injury in LPS-induced sepsis mice. In addition, AMEB could inhibit pyroptosis and the activiation of NLRP3 inflammasome. The inhibiting function of AMEB on the activiation of NLRP3 inflammasome is weakened following si-NLRP3 transfection. Moreover, AMEB exerted anti-pyroptosis effect via targeting NLRP3 protein. Our findings first indicate NLRP3 is an effective druggable target for septic encephalopathy related brain injury, and also provide a candidate-AMEB for the treatment of septic encephalopathy. These emerging findings on AMEB in models of sepsis suggest an innovative approach that may be beneficial in the prevention of septic encephalopathy. [Display omitted] [ABSTRACT FROM AUTHOR]

Ischemic stroke (IS) is characterized as a detrimental cerebrovascular disease with high mortality and disability. Ferroptosis is a novel mechanism involved in neuronal death. There is a close connection between IS and ferroptosis, and inhibiting ferroptosis may provide an effective strategy for treating IS. Our previous investigations have discovered that kellerin, the active compound of Ferula sinkiangensis K. M. Shen, possesses the capability to shield against cerebral ischemia injury. Our objective is to clarify the relationship between the neuroprotective properties of kellerin against IS and its ability to modulate ferroptosis, and investigate the underlying regulatory pathway. We investigated the impact and mechanism of kellerin in C57BL/6 mice underwent middle cerebral artery occlusion/reperfusion (MCAO/R) as well as SH-SY5Y cells exposed to oxygen-glucose deprivation/ re-oxygenation (OGD/R). The roles of kellerin on neurological severity, cerebral infarction and edema were investigated in vivo. The regulatory impacts of kellerin on ferroptosis, mitochondrial damage and Akt/Nrf2 pathway were explored. Molecular docking combined with drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) were performed to analyze the potential target proteins for kellerin. Kellerin protected against IS and inhibited ferroptosis in vivo. Meanwhile, kellerin improved the neuronal damage caused by OGD/R and suppressed ferroptosis by inhibiting the production of mitochondrial ROS in vitro. Further we found that kellerin directly interacted with Akt and enhanced its phosphorylation, leading to the increase of Nrf2 nuclear translocation and its downstream antioxidant genes expression. Moreover, kellerin's inhibitory effect on ferroptosis and mitochondrial ROS release was eliminated by inhibiting Akt/Nrf2 pathway. Our study firstly demonstrates that the neuroprotective properties of kellerin against IS are related to suppressing ferroptosis through inhibiting the production of mitochondrial ROS, in which its modulation on Akt-mediated transcriptional activation of Nrf2 plays an important role. This finding shed light on the potential mechanism that kellerin exerts therapeutic effects in IS. [Display omitted] [ABSTRACT FROM AUTHOR]

Among adults, stroke is the main causes of mortality and permanent disability. Neuroinflammation is one of the main causes of stoke-mediated neuronal death. Our previous study revealed that (E)-5-(2-(Quinolin-4-yl) vinyl) benzene-1, 3-diol (RV01), a quinolinyl analog of resveratrol, inhibits microglia-induced neuroinflammation and safeguards neurons from inflammatory harm. The preventive role of RV01 in ischemic stroke and its underlying cellular mechanisms and molecular targets remain poorly understood. To investigate whether RV01 alleviates ischemia-reperfusion (I/R) injury by inhibiting microglia-mediated neuroinflammation and determine the potential molecular mechanisms and targets by which RV01 inhibits the I/R-mediated microglia activation. Rat middle cerebral artery occlusion and reperfusion (MCAO/R) and BV-2 or primary microglial cells oxygen-glucose deprivation and reperfusion (OGD/R) models were established. The neurological behavior scores, 2, 3, 5-triphenyl tetrazolium chloride staining and immunofluorescence were used to detect the neuroprotective effect of RV01 in the MCAO/R rats. In addition, the mRNA expression levels of IL-6, TNF-α, and IL-1β were detected to reveal the antineuroinflammatory effect of RV01. Moreover, a western blot assay was performed to explore the protein expression changes in NF-κB-mediated neuroinflammation. Finally, we identified TLR4 as an RV01 target through molecular docking, drug sensitivity target stability analysis, cellular thermal shift analysis, and surface plasmon resonance techniques. RV01 reduced the infarct volume and neurological deficits, increased the rotarod duration, and decreased the number of rightward deflections in the MCAO/R rats. RV01 inhibited the NF-κB signaling pathway in vitro and in vivo , as demonstrated by the reduction in the transcription factor p65-mediated expression of several inflammatory factors including IL-6, TNF-α, and IL-1β. Further studies showed that its protective effect was associated with targeting the TLR4 protein. Notably, the anti-inflammatory effect of RV01 was markedly reinforced by the TLR4 knockdown, but inhibited by the overexpression of TLR4. Results revealed that the conditioned medium derived from the RV01-treated BV-2 cells significantly decreased the OGD/R-mediated neuronal damage. Our results are the first to reveal the protective effects of RV01 on cerebral ischemia, depending on its inhibitory effect on the NF-κB pathway by targeting TLR4. RV01 could be a potential protective agent in ischemic stroke treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

• A new method of estimating the instant case fatality rate of COVID-19 was established. • The average case fatality rate in China was 6.1 ± 2.9%, and it finally stabilized at 5.7% in April, while it was 1% in China except Hubei Province. • The fatality rate of COVID-19 in China was underestimated. The outbreak of coronavirus disease 2019 (COVID-19) in China has been basically controlled. However, the global epidemic of COVID-19 is worsening. We established a method to estimate the instant case fatality rate (CFR) and cure rate of COVID-19 in China. A total of 82 735 confirmed cases released officially by the Chinese authorities from December 8, 2019 to April 18, 2020 were collected. The estimated diagnosis dates of deaths and cured cases were calculated based on the median cure time or median death time of individual cases. Following this, the instant CFR was calculated according to the number of deaths and cured cases on the same estimated diagnosis date. In China, the instant CFR of COVID-19 was 3.8–14.6% from January 1 to January 17; it then declined gradually and stabilized at 5.7% in April. The average CFR in China was 6.1 ± 2.9%, while the CFR was 1.0 ± 0.4% in China except Hubei Province. The cure rate of COVID-19 was 93.9 ± 2.9% in China, and stabilized at 94.3%, while it was 99.0 ± 0.4% in China except Hubei Province. The instant CFR of COVID-19 in China overall was much higher than that in China except Hubei Province. The CFR of COVID-19 in China was underestimated. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), the most prevalent form of dementia, remains untreatable. One of the factors that contributes to its progression is microglia-mediated inflammation. Pterostilbene, a compound isolated from Chinese dragon's blood, can reduce inflammation caused by overactive microglia. However, its effects on AD transgenic animals and the possible underlying mechanism remain unknown. We evaluated the effect of pterostilbene on learning and memory difficulties in transgenic APP/PS1 mice. We used immunofluorescence to detect microglial activation and Aβ aggregation. We explored the cellular mechanism of pterostilbene by establishing LPS- stimulated BV2 cells and oAβ 1 – 42 - exposed HEK 293T cells that overexpress TLR4 and/or MD2 via lentivirus. We applied flow cytometry and immunoprecipitation to examine how pterostilbene regulates TLR4 signaling. Pterostilbene enhanced the learning and memory abilities of APP/PS1 mice and reduced microglial activation and Aβ aggregation in their hippocampus. Pterostilbene alleviated oAβ 1 – 42 -induced inflammation, which required the involvement of MD2. Pterostilbene disrupted the binding between TLR4 and MD2, which may further prevent TLR4 dimerization and subsequent inflammatory response. Moreover, pterostilbene restored the impaired endocytosis of oAβ 1 – 42 through an autophagy-dependent mechanism. This is the first demonstration that pterostilbene can potentially treat AD by blocking the interaction of TLR4 and MD2, thereby suppressing TLR4-mediated inflammation. [Display omitted] [ABSTRACT FROM AUTHOR]

Five new formyl phloroglucinol meroterpenoids (FPMs), eucalteretials A−E ( 1 – 5 ), along with eight known analogues ( 6 − 13 ), were isolated from the twigs and leaves of Eucalyptus tereticornis . Their structures were established mainly by analysis of comprehensive spectroscopic data, and their absolute configurations were determined by electron circular dichroism (ECD) calculation. Within FPMs, both 1 and 2 are rare adducts of formyl phloroglucinol moiety and germacrene unit with different coupling patterns, respectively. Compound 3 exhibited significant cytotoxicity against HCT116 cell line with an IC 50 value of 4.76 μM. In addition, 5 and 9 were proved to be rare topoisomerase I (Top1) inhibitors. [ABSTRACT FROM AUTHOR]

The two main components of commercial soybean-based adhesives (SA), polyamidoamine-epichlorohydrin (PAE) resin and soybean protein, are extremely ion-sensitive. When SA is used to bond dyed wood substance and/or mix with anion dyes for labelling wood composites during commercial manufacturing, the regularly used anion dyes in the wood industry may produce significant differences in the bonding capabilities of SA. In the current study, three common tricolor anion dyes in the wood industry were chosen to evaluate their impacts on the structures and properties of soybean protein, PAE resin, and PAE-modified SA, respectively. Analytical data from FTIR, XRD, TGA, NMR, sol-gel test, and plywood evaluation indicated that dye ions had varying effects on the bonding properties of SAs. The addition of chosen red and yellow dyes to SAs enhanced plywood cycling wet strengths by 41.7–42.8%, whereas the blue dye had little impact. The promoter interactions of red- and yellow-dye ions on the unfolding of globular structures of soybean protein, the self-crosslinking of PAE resin, and the sufficient co-crosslinking of soybean protein by PAE resin all contributed to the formation of compact three-dimensional networks of cured SAs. As a result, this work illuminates a novel method for conveniently improving the bonding capabilities of SAs by adding appropriate dyes. • Bonding properties of soybean-based adhesive (SA) affected by dyes were evaluated. • Cycled wet strength of plywood bonded by dye-added SAs improved by 41.7–42.8%. • Effects of dye ions on structures of soybean protein and PAE resin were revealed. • Interactions of dye ions on structures and properties of SA were elucidated. [ABSTRACT FROM AUTHOR]

Ischemic stroke (IS) is considered as a serious cerebral vascular disease. Ferroptosis is a novel type of regulated cell death (RCD), that closely related to the occurrence and progress of IS. Loureirin C, a type of dihydrochalcone compound derived from the Chinese Dragon's blood (CDB). The effective components extracted from CDB have shown neuroprotective effects in ischemia reperfusion models. However, the role of Loureirin C in mice after IS is not well understood. Thus, it is worth to identify the effect and mechanism of Loureirin C on IS. The present research aims to prove the existence of ferroptosis in IS and explore whether Loureirin C can inhibit ferroptosis by regulating nuclear factor E2 related factor 2 (Nrf2) pathway in mice and exert neuroprotective effects on IS models. Middle cerebral artery occlusion and reperfusion (MCAO/R) model was established to evaluate the occurrence of ferroptosis and the potential Loureirin C brain-protective effect in vivo. The analysis of free iron, glutamate content, reactive oxygen species (ROS) and lipid peroxidation levels, along with transmission electron microscope (TEM) was applied to prove the existence of ferroptosis. The function of Loureirin C on Nrf2 nuclear translocation was verified by immunofluorescence staining. In vitro , primary neurons and SH-SY5Y cells were processed with Loureirin C after oxygen and glucose deprivation-reperfusion (OGD/R). ELISA kits, western blotting, co-immunoprecipitation (Co-IP) analysis, immunofluorescence, and quantitative real-time PCR were devoted to proving the neuroprotective effects of Loureirin C on IS via regulating ferroptosis and Nrf2 pathways. The results showed that Loureirin C not only dramatically alleviated brain injury and inhibited neurons ferroptosis in mice after MCAO/R, but also dose-dependently reduce ROS accumulation in ferroptosis after OGD/R. Further, Loureirin C inhibits ferroptosis by activating Nrf2 pathway, and promoting nuclear translocation of Nrf2. Besides, Loureirin C increases heme oxygenase 1 (HO-1), quinone oxidoreductase 1 (NQO1) and glutathione peroxidase 4 (GPX4) content after IS. Intriguingly, the anti-ferroptosis effect of Loureirin C is weakened by Nrf2 knockdown. Our discoveries first revealed that the inhibitory action of Loureirin C on ferroptosis may greatly depend on its adjusting effect on the Nrf2 pathway, suggesting that Loureirin C could act as a novel anti-ferroptosis candidate and play a therapeutic role in IS. These novel discoveries on the role of Loureirin C on IS models reveal an innovative method that may contribute to neuroprotection for the prevention of IS. [Display omitted] [ABSTRACT FROM AUTHOR]

The substitution of environmentally friendly, renewable soybean-based adhesives (SBAs) for formaldehyde-based synthetic resins to produce formaldehyde-free wood composites is of great significance for resource recycling and environmental protection. However, SBA-bonded wood composites often exhibit great variations in bonding properties, due to the diverse interactions of the extractive components in wood. In this study, the extracts of four typical commercial fast-growing timbers were isolated, and their effects on the structures and properties of the SBAs were systematically investigated using FTIR, NMR, TGA, contact angle, buffer capacity, sol–gel test, and plywood evaluation. The analytical data indicated that some of the wood extracts could cause important effects on the bonding properties of the SBAs by impacting the PAE cross-linking capacity and unfolding degree of the globular soybean proteins. Fast-growing hardwood extracts from poplar and eucalyptus timbers containing active groups resulted in increased cross-linking density and improved water resistance of the SBAs. Meanwhile, fast-growing softwood extracts from Chinese fir and Scotch pine containing inert hydrophobic components had slight impacts on PAE cross-linking, but resulted in the agglomeration of unfolded soybean proteins. This formed a weak boundary layer on the wood surface, causing a significant decrease in the water resistance of the SBAs by >35%. These findings presented available analytic approaches of wood extract–SBA interactions and useful guidance for the proper applications of SBAs in the commercial production of wood composites. • The adhesion of soybean adhesive impacted by wood extracts was investigated. • The interactions of the wood extracts with the crosslinker PAE were characterized. • The interactions of wood extracts with soybean proteins were evaluated. • The structure–property changes of the soybean adhesives caused by the wood extracts were revealed. [ABSTRACT FROM AUTHOR]

To pursue high photocatalytic activity in visible-light region, the Fe(III) modified BiOCl ultrathin nanosheet (Fe(III)@BOC NS) has been firstly synthesized via a facile solvothermal approach. The morphological and compositional characterizations reveal that the thickness of the as-prepared Fe(III)@BOC NS is less than 5 atomic layer with the exposure of active [001] facets. And the Fe(III) doping and surface grafting result in a 0.58 eV down-shift of the BiOCl conduction band minimum extending the light absorption from ultraviolet light to visible light region, as well as a promoted interfacial charge transfer upon visible light irradiation. Meanwhile, the Fe(III) modification introduces unique active sites on the surface of ultrathin nanosheet facilitating the surface reaction. Moreover, both of the appropriate self-induced electric field of [001] facets, and the shortened charge carrier diffusion length of ultrathin nanosheet enhance the separation and transfer efficiency of charge carriers. Therefore, by taking those advantages, we experimentally demonstrate that the Fe(III)@BOC NS is a high-efficiency visible-light photocatalyst for both of environment remediation and water splitting. [ABSTRACT FROM AUTHOR]

The effect of ammonium sulfate ((NH4)2SO4) and urea (CO(NH2)2) on polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) formation from active carbon was investigated in this study. Both additives could significantly inhibit PCDD/F formation, and PCDD/F (TEQ) generation was reduced to 98.5% (98%) or 64.5% (77.2%) after 5% (NH4)2SO4 or CO(NH2)2 was added into model ash, respectively. The inhibition efficiency of PCDDs was higher than the value of PCDFs, however, the reduction of PCDD/F yield was mainly from PCDFs decreasing. In addition, the solid-phase products were reduced more than the gas-phase compounds by inhibitors. By the measurement of chlorine emission in the phase of ion (Cl[Cl−]) and molecule gas (Cl[Cl2]), it was observed that both Cl[Cl−] and Cl[Cl2] were reduced after inhibitors were added into ash. Cl[Cl2] was reduced to 51.0% by urea addition, which was supposed as one possible mechanism of PCDD/F inhibition. [ABSTRACT FROM AUTHOR]

Defects such as oxygen vacancies play an important role in the photoactivation processes. However, the roles of surface and bulk defects in photocatalytic water splitting are still ambiguous. This paper would report a new method to introduce surface and bulk defects in SrTiO 3 nanocrystals. Melamine was used as a reducing agent which would be carbonized under the N 2 atmosphere. During thermal decomposition of melamine, reductive NH 3 and C would generate in succession to reduce the SrTiO 3 nanocrystals. The relative concentration ratio of bulk defects to surface defects in SrTiO 3 nanocrystals would be tuned from 0.78 to 2.55 after reduction treatment. Furthermore, the band structures of surface and bulk defects in SrTiO 3 were studied by DFT. The surface oxygen defects would make the band structure shift to a high energy level, while the bulk oxygen defects of SrTiO 3 would restore the energy levels of the band structure. Thus, photocatalytic overall water splitting activity would improve significantly by rational relative concentration ratio of bulk defects to surface defects in SrTiO 3. • Melamine was used as reducing agent to introduce defects in SrTiO 3. • The relative concentration ratio of bulk defects to surface defects was tuned. • The surface and bulk defects made different contribution to the band structure. • OWS improve significantly by rational concentration ratio of bulk to surface defects. [ABSTRACT FROM AUTHOR]

• Bi 3−x Y x O 4 Cl solid solution were successfully synthesized by solid-phase method. • The absorption edge of Bi 3−x Y x O 4 Cl could be adjusted from about 500–740 nm. • The conduction band minimum energy satisfied the redox potential for both H+/H 2. • Bi 3−x Y x O 4 Cl solid solution showed the visible light photocatalytic H 2 evolution activity. [Display omitted] The solid solution constructed by two or more semiconductors with different bandgaps can effectively modulate the energy band, satisfying the redox potential for both H+/H 2 and O 2 /H 2 O. In this paper, Sillen-Aurivillius compounds with layered structure Bi 3 O 4 Cl and Y 3 O 4 Cl solid solution (Bi 3−x Y x O 4 Cl) were successfully synthesized by the solid-phase method. The absorption edge of Bi 3−x Y x O 4 Cl could be dramatically changed from about 500–740 nm with the increase of Bi elements, which accounted for the entire UV-Vis region of the solar spectrum. Furthermore, the bandgaps for Bi 3−x Y x O 4 Cl could be adjusted from about 2.6–2.0 eV with the decreased Y/Bi ratio from 2 to 0.2. Significantly, the conduction band minimum energy (CBM) of Bi 3−x Y x O 4 Cl all satisfied the redox potential for H+/H 2 , which showed excellent visible-light photocatalytic water splitting. [ABSTRACT FROM AUTHOR]