Blockage of mechanosensitive Piezo1 channel alleviates the severity of experimental malaria-associated acute lung injury.

BACKGROUND: Malaria-associated acute lung injury (MA-ALI) is a well-recognized clinical complication of severe, complicated malaria that is partly driven by sequestrations of infected red blood cells (iRBCs) on lung postcapillary induced impaired blood flow. In earlier studies the mechanosensitive Piezo1 channel emerged as a regulator of mechanical stimuli, but the function and underlying mechanism of Piezo1 impacting MA-ALI severity via sensing the impaired pulmonary blood flow are still not fully elucidated. Thus, the present study aimed to explore the role of Piezo1 in the severity of murine MA-ALI. METHODS: Here, we utilized a widely accepted murine model of MA-ALI using C57BL/6 mice with Plasmodium berghei ANKA infection and then added a Piezo1 inhibitor (GsMTx4) to the model. The iRBC-stimulated Raw264.7 macrophages in vitro were also targeted with GsMTx4 to further explore the potential mechanism. RESULTS: Our data showed an elevation in the expression of Piezo1 and number of Piezo1+-CD68+ macrophages in lung tissues of the experimental MA-ALI mice. Compared to the infected control mice, the blockage of Piezo1 with GsMTx4 dramatically improved the survival rate but decreased body weight loss, peripheral blood parasitemia/lung parasite burden, experimental cerebral malaria incidence, total protein concentrations in bronchoalveolar lavage fluid, lung wet/dry weight ratio, vascular leakage, pathological damage, apoptosis and number of CD68+ and CD86+ macrophages in lung tissues. This was accompanied by a dramatic increase in the number of CD206+ macrophages (M2-like subtype), upregulation of anti-inflammatory cytokines (e.g. IL-4 and IL-10) and downregulation of pro-inflammatory cytokines (e.g. TNF-α and IL-1ß). In addition, GsMTx4 treatment remarkably decreased pulmonary intracellular iron accumulation, protein level of 4-HNE (an activator of ferroptosis) and the number of CD68+-Piezo1+ and CD68+-4-HNE+ macrophages but significantly increased protein levels of GPX4 (an inhibitor of ferroptosis) in experimental MA-ALI mice. Similarly, in vitro study showed that the administration of GsMTx4 led to a remarkable elevation in the mRNA levels of CD206, IL-4, IL-10 and GPX-4 but to a substantial decline in CD86, TNF-α, IL-1ß and 4-HNE in the iRBC-stimulated Raw264.7 cells. CONCLUSIONS: Our findings indicated that blockage of Piezo1 with GsMTx4 alleviated the severity of experimental MA-ALI in mice partly by triggering pulmonary macrophage M2 polarization and subsequent anti-inflammatory responses but inhibited apoptosis and ferroptosis in lung tissue. Our data suggested that targeting Piezo1 in macrophages could be a promising therapeutic strategy for treating MA-ALI.

Cadinane sesquiterpenes from the stems and branches of Illicium ternstroemioides.

Three new cadinane sesquiterpenes (1-3) and three known sesquiterpenes were isolated from the stems and branches of Illicium ternstroemioides A. C. Smith. The structures of the new compounds were elucidated by extensive analysis of spectroscopic and HRESIMS data. The structures of illiternins A-C (1-3) were confirmed by single crystal X-ray diffraction, allowing for the determination of their absolute configurations. Compounds 3 and 6 exhibited antiviral activity against Coxsackievirus B3 with IC50 values of 33.3 and 57.7 µM, respectively.

[Vertical Migration Characteristics and Fate of Heavy Metals from Zinc Smelting Slag in Soil Profile].

To investigate the influence of heavy metals in smelting waste residue on the quality of soil and groundwater, a simulation column experiment was conducted to study the migration characteristics of heavy metals from the leaching solution of zinc volatilizing kiln residue in the site soil profile under continuous or intermittent leaching for 90 days. The concentrations of Cd, Cu, Pb, and Zn in leachate and their accumulation, chemical fractions, and particle size distribution characteristics in the soil profile were analyzed, and the retention mechanism of heavy metals was also discussed. The results showed that the concentration of heavy metals in the soil column leachate decreased rapidly after reaching the peak at the earlier leaching stage, and the Cd concentration far exceeded the threshold limit of 0.1 mg·L-1(class Ⅳ) of the Quality Standard for Groundwater(GB/T 14848-2017), indicating that there was Cd pollution risk of groundwater. The soil profile had a great adsorption capacity for heavy metals in the waste residue. Cd, Cu, Pb, and Zn were predominately accumulated in the shallow soil depth(0-10 cm), which was 237-429, 1.25-16.2, 1.38-2.31, and 1.79-3.17 times of the content of corresponding heavy metals in the soil profile before leaching, respectively. The migration distance of heavy metals in the slag under continuous leaching was longer than that under intermittent leaching, and Cd was significantly accumulated in the deep layer of the soil column. The contribution of soil coarse particles(0.5-2.0 mm) to the total cumulative amount of Cd, Cu, and Zn was larger, whereas Pb was more prone to accumulate in the particle size of<0.25 mm. The results of BCR sequential extraction fraction showed that the accumulated Cd, Cu, and Zn in shallow soil depth were mainly present in the weak acid extraction, accounting for 62.4%-76.7%, 72.0%-95.8%, and 67.6%-85.8% of total content, respectively. The X-ray diffraction(XRD) and Fourier transform infrared spectroscopy(FTIR) analysis showed that exogenous heavy metals in slag entering the soil would not form a stable mineral phase within 90 days, and the soil hydroxyl(-OH) and carbonyl(C=O) functional groups and iron aluminum silicate oxides were the main retention factors.

Prenylated C6-C3 derivatives from the root of Illicium ternstroemioides with antiviral activity.

Six previously undescribed prenylated C6-C3 derivatives (1-6) were isolated from the root of Illicium ternstroemioides A. C. Smith. Their structures were elucidated based on extensive spectroscopic analyses (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of 1-3 were determined using electronic circular dichroism (ECD), and Mo2(OAc)4 induced circular dichroism (ICD). Compound 3 exhibited weak activity against Coxsackievirus B3 with an IC50 value of 33.3 µM, and compound 5 exhibited more potent activity against Coxsackievirus B3 with an IC50 value of 6.4 µM.

Insights into differences between spore-assisted and pellet-assisted microalgae harvesting using a highly efficient fungus: Efficiency, high-value substances, and mechanisms.

To achieve efficient and low-cost microalgae harvesting, investigations were conducted on the harvesting efficiency and potential mechanisms of Chlorella sp. HQ by filamentous fungi using two strategies, fungal spore-assisted harvesting (FSH) and fungal pellet-assisted harvesting (FPH). Five of the 19 fungal species isolated from domestic sewage could form pellets, and Aspergillus niger HW8-1 comprised the highest harvesting efficiencies of 99.17 % and 88.70 % for FPH and FSH, respectively. FSH had 2-3 times more lipids and polysaccharides in fungus-alga pellets and caused richer saturated and monounsaturated fatty acids compared with FPH. Moreover, by optimizing the microalgae preculture time, glucose concentration, and microalgae initial density, the contents of high-value substances, such as lipids, polysaccharides, and proteins of fungus-alga pellets after FPH were improved from 5.96 %, 5.67 %, and 7.27 % to 20.18 %, 24.34 % and 10.48 %, respectively. Furthermore, fungal pellets secreted more extracellular polymeric substances (EPS) during FPH than those by FSH, which could chemisorb algal cells by lowering the surface potential of fungal pellets. FPH caused algal cells to cover the outside, which increased the light exposure area of algae, thereby increasing the photosynthesis rate, whereas FSH mainly captured microalgae physically through mycelium entanglement.

Malaria-derived exosomes exacerbate liver injury during blood stage of Plasmodium berghei infection.

Liver injury is a common clinical feature of Plasmodium spp. infection and contributes to multi-organ failure of severe malaria. Malaria-derived exosomes (MD-Exos) have recently engaged as key mediators in parasite-host interactions, modulating the subsequent pathogenic process. However, the role of MD-Exos in malaria-related liver injury and the underlying mechanisms remain unclear. Herein, exosomes from C57BL/6 mice infected with or without P. berghei ANKA serum (namely inf-Exos or un-Exos) were isolated and characterized by transmission electron microscopy, western blotting, and nanoparticle tracking analysis. The miRNAs profiling between inf-Exos and un-Exos were generated using RNA-seq and qPCR. The functions of inf-Exos on liver injury were investigated after two types of exosomes injected into mice intravenously (i.v.), by examining histopathological and apoptotic changes, macrophage polarization, and pro-inflammatory response. The infected red blood cells-stimulated mouse Raw264.7 macrophage cells targeted by inf-Exos or un-Exos were cultured for further study and verification the potential mechanisms. We found that both inf-Exos and un-Exos displayed a typical cup-shaped structure with a diameter of 60-200 nm, and had a positive expression of exosomal markers (e.g., CD9, CD63, and CD81). Compared with infected control mice, the treatment of inf-Exos but not un-Exos dramatically enhanced peripheral blood parasitemia and ECM incidence, exacerbated liver histopathological damage, elevated numbers of liver apoptotic cells, CD68+and CD86+ macrophages. The CD68+-TREM-1+ macrophages in liver tissues and the mRNA levels of pro-inflammatory cytokines (e.g., iNOS, TNF-α, IL-1ß, and IL-6) were increased by inf-Exos treatment in vivo. Meanwhile, the treatment of inf-Exos resulted in a substantial increase of the mRNA levels of CD86, iNOS, TNF-α, IL-1ß, and IL-6, but led to a remarkable decrease of Bcl-6 and SOCS-1 in Raw264.7 cells stimulated with iRBC in vitro. Notably, compared to un-Exos, five types of miRNAs (including miR-10a-5p, miR-10b-5p, miR-155-5p, miR-205-5p, and miR-21a-5p), that were previously reported to target Bcl-6 or SOCS-1, present higher abundance on inf-Exos, as demonstrated by RNA-seq and qPCR. Collectively, our data suggest that inf-Exos exacerbate malaria-induced liver pathology via triggering excessive pro-inflammatory response and promoting macrophage M1 polarization. Our findings will provide new insights into the roles of inf-Exos in malaria parasite-host interaction and pathogenesis of liver injury.

Analysis of ocular structural parameters and higher-order aberrations in Chinese children with myopia.

BACKGROUND: Myopia and high myopia are global public health concerns. Patients with high myopia account for 0.5%-5.0% of the global population. AIM: To examine diopters, axial length (AL), higher-order aberrations, and other ocular parameters in Chinese children with myopia, to analyze the influence of structural parameters associated with myopia on visual quality, and to provide a theoretical basis for the prevention and treatment of childhood myopia and high myopia. METHODS: This study included 195 children aged 6-17 years with myopia. The AL was measured with an ultrasonic ophthalmic diagnostic instrument, and the aberrations, corneal curvature (minimum K1, maximum K2, and average Km), central corneal thickness, anterior chamber depth, and anterior chamber angle were measured using a Sirius three-dimensional anterior segment analyzer. Using a standard formula, the corneal radius of curvature R (337.3/Km) and AL/R values were obtained. RESULTS: The diopter of high myopia compared with low-middle myopia was correlated with age and AL (r = -0.336, -0.405, P < 0.001), and AL of high myopia was negatively correlated with K1, K2, and Km (r = -0.673, -0.661, and -0.680, respectively; P < 0.001), and positively correlated with age and the anterior chamber depth (r = 0.214 and 0.275, respectively; P < 0.05). AL/R was more closely related to diopter than AL in children with myopia, and 94.4% of children with myopia had an AL/R of > 3.00. CONCLUSION: The ocular structural parameters of children change because of different diopters. AL/R is more specific and sensitive than AL in evaluating the refractive status of myopia in children. An AL/R of > 3.00 may be used as a specific index of myopia in children. There are differences in AL/R between high myopia and low-middle myopia, which can be used for the classification of ametropia. The degree of myopia has a certain influence on higher-order aberrations.

Optimal clutch size for quality control of bisexual and Wolbachia-infected thelytokous lines of Trichogramma dendrolimi Matsumura (Hymenoptera: Trichogrammatidae) mass reared on eggs of a substitutive host, Antheraea pernyi Guérin-Méneville (Lepidoptera: Saturniidae).

BACKGROUND: Trichogramma dendrolimi has been widely used in augmentative biocontrol of lepidopteran pests in China. In mass production of T. dendrolimi using Antheraea pernyi eggs as substitutive hosts, which are large in size, as clutch size is a parameter of importance to produce high quality parasitoids. Here, we aimed to determine the optimal clutch size for the bisexual Wolbachia-uninfected line (TdB) and Wolbachia-infected thelytokous line (TdT) of T. dendrolimi reared on A. pernyi eggs. RESULTS: A medium clutch size of 42.75 to 62.27 for TdB and 52.93 to 57.14 for TdT was optimal to maximize fitness-correlated traits of parasitoid individual. The optimal clutch sizes with maximized parameters included adult emergence rate, adult body size, adult longevity, fecundity, and sum of fecundity of all females per brood were 58.31 (86.00%), 42.75 (231.11 µm), 50.92 (2.69 days), 62.27 (150.89 eggs), and 83.25 (7926.33 eggs) for TdB and 57.14 (94.54%), 52.93 (236.97 µm), 53.64 (2.62 days), 56.80 (161.01 eggs), and 70.10 (8579.71 eggs) for TdT. The TdT had a shorter adult longevity, longer development time, and higher adult emergence rate than did its non-infected bisexual counterpart. CONCLUSION: A medium brood size in a A. pernyi egg host was optimal to produce offspring parasitoids with higher fitness parameters for both bisexual Wolbachia-uninfected and thelytokous Wolbachia-infected lines of T. dendrolimi. The determination of optimal clutch size for T. dendrolimi will provide the reference for the quality control of T. dendrolimi production and improvement of the field performance of the wasps. © 2020 Society of Chemical Industry.

Thermodynamic Properties of Ammonia Production from Hydrogenation of Alkali and Alkaline Earth Metal Amides.

Thermodynamic properties of alkali and alkaline earth metal amides are critical for their performance in hydrogen storage as well as catalytic ammonia synthesis. In this work, the ammonia equilibrium concentrations of LiNH2 , KNH2 and Ba(NH2 )2 at ca.10 bar of hydrogen pressure and different temperatures were measured by using a high-pressure gas-solid reaction system equipped with a conductivity meter. Hydrogenation of KNH2 gives the highest ammonia equilibrium concentration, followed by Ba(NH2 )2 and LiNH2 . Based on these data, the entropy and enthalpy changes of the reaction of ANH2 +H2 →AH+NH3 (A=Li, K, and Ba) were obtained from the van't Hoff equation. These thermodynamic parameters provide important information on the understanding of metal amides in catalytic ammonia synthesis reaction.

Spatiotemporal Analysis of the Malaria Epidemic in Mainland China, 2004-2014.

The purpose of this study is to characterize spatiotemporal heterogeneities in malaria distribution at a provincial level and investigate the association between malaria incidence and climate factors from 2004 to 2014 in China to inform current malaria control efforts. National malaria incidence peaked (4.6/100,000) in 2006 and decreased to a very low level (0.21/100,000) in 2014, and the proportion of imported cases increased from 16.2% in 2004 to 98.2% in 2014. Statistical analyses of global and local spatial autocorrelations and purely spatial scan statistics revealed that malaria was localized in Hainan, Anhui, and Yunnan during 2004-2009 and then gradually shifted and clustered in Yunnan after 2010. Purely temporal clusters shortened to less than 5 months during 2012-2014. The two most likely clusters detected using spatiotemporal analysis occurred in Anhui between July 2005 and November 2007 and Yunnan between January 2010 and June 2012. Correlation coefficients for the association between malaria incidence and climate factors sharply decreased after 2010, and there were zero-month lag effects for climate factors during 2010-2014. Overall, the spatiotemporal distribution of malaria in China changed from relatively scattered (2004-2009) to relatively clustered (2010-2014). As the proportion of imported cases increased, the effect of climate factors on malaria incidence has gradually become weaker since 2011. Therefore, new warning systems should be applied to monitor resurgence and outbreaks of malaria in mainland China, and quarantine at borders should be reinforced to control the increasingly trend of imported malaria cases.

Suppression of EIF4G2 by miR-379 potentiates the cisplatin chemosensitivity in nonsmall cell lung cancer cells.

Although microRNAs and EIF4G2 are both known to play pivotal roles in cancer progression, it remains unknown whether these pathways regulate chemosensitivity in a coordinated manner. Here, we show that miR-379 expression is significantly downregulated in chemoresistant nonsmall cell lung cancer (NSCLC) tissues and cells. Manipulation of miR-379 levels could alter the in vitro and in vivo cisplatin (CDDP) resistance in lung cancer (LCa) cells. Mechanistically, miR-379 potentiated LCa chemosensitivity via modulation of CDDP-induced apoptosis by directly targeting the EIF4G2 3'UTR. Additionally, we observed an inverse correlation between miR-379 and EIF4G2 expression in LCa tissues from patients with CDDP-based chemotherapy. Together, our findings shed new light on the potential involvement of miR-379/EIF4G2 cascade in the pathogenesis of CDDP resistance in LCa.

A colorimetric agarose gel for formaldehyde measurement based on nanotechnology involving Tollens reaction.

Gold nanoparticles (Au NPs) coupled with Tollens reagent were used for measuring formaldehyde. Au@Ag core-shell NPs were formed along with distinct color changes from pink to deep yellow. This colorimetric system was further immobilized into an agarose gel, which was used for monitoring of gaseous formaldehyde.

[Study on irritation of calcium oxalate crystal in raw Pinellia ternata].

OBJECTIVE: Confirm the irritation of needle-like calcium oxalate crystals in raw Pinellia ternata. METHOD: Comparing the irritations of raw P. ternate containing calcium oxalate crystals, the raw P. ternate no containing calcium oxalate crystals, the pure needle-like calcium oxalate crystals isolated from raw P. ternata, the extracts of water and various solvents from raw P. ternate. by using the model of rabbits' eyes. Studying the quantity effect relationship of different concentration suspensions of needle-like calcium oxalate crystal isolated from raw P. ternate on rabbits' eyes. Observing the shape and appearance of calcium oxalate crystals in raw P. ternate and raw India Madder Root by the electro microscope and comparing their irritation degrees with the same contents of calcium oxalate crystals. RESULT: Calcium oxalate crystals in raw P. ternata showed very strong irritation property. Under the same content of calcium oxalate crystals, the irritation of raw P. ternata and pure needle-like calcium oxalate crystals isolated from raw P. ternate had no significant difference. The concentrations of needle-like calcium oxalate crystals were do relative to the degree of irritation on rabbits' eyes and they showed undoubted quantity-effect relationship. CONCLUSION: Calcium oxalate crystal is the irritation component in raw P. ternata.