The flow of calcium ions (Ca
2+
) is involved in numerous vital activities of
Toxoplasma gondii
. Calreticulin is a type of Ca
2+
-binding protein in the endoplasmic reticulum (ER) that is involved ...in Ca
2+
signaling pathway regulation, Ca
2+
storage, and protein folding. In this work, the calreticulin (CALR), a protein predicted to possess a conserved domain of calreticulin in
T. gondii
, was characterized. The CALR localized in the ER. Using reverse genetics, we discovered that CALR is not necessary for the lytic cycle, including invasion and replication. However, depletion of CALR affected microneme secretion triggered by A23187, which is a Ca
2+
ionophore used to increase cytoplasmic Ca
2+
concentration. Furthermore, we discovered that CALR influences Ca
2+
release. Transcriptomic comparison between
Δcalr
and
Δku80
parasites showed that 226 genes in the
Δcalr
parasites were significantly downregulated (
p
< 0.05). The cellular biological functions of the downregulated genes were mainly involved in calmodulin-dependent protein kinase pathways. Furthermore, in the absence of CALR, tachyzoites were still able to cause acute infection in mice. These results imply that by influencing ER Ca
2+
release content, CALR may further impair the ionophore-induced secretion of the parasite. However, this protein is not required for the completion of the parasite’s lytic cycle or for the acute virulence of the parasite.
Despite the importance of medication adherence in treatment effectiveness, little is known about the association between medication non-adherence and self-inflicted violence behaviors. We aimed to ...assess whether medication non-adherence increased the risk of self-inflicted violence behaviors among schizophrenics in communities (hypothesis 1) and whether the dose-response relationship existed (hypothesis 2).
This 12-year cohort study in western China recruited 292,667 community-dwelling schizophrenics. The proportion of regular medication (PRM) was calculated by dividing the time of "regular adherence" by the total time of antipsychotic treatment during follow-up period as an indicator of medication adherence. For hypothesis 1, medication adherence was designated as a binary variable with a threshold of 0.8 (PRM); for hypothesis 2, medication adherence was specified as five-category and continuous variables, respectively. Inverse probability weighting and mixed effects Cox proportional hazards models were conducted for confounders control and survival analyses.
One hundred eighty-five thousand eight hundred participants were eligible for the final analyses, with a mean age of 47.49 years (SD 14.55 years), of whom 53.6% were female. For hypothesis 1, the medication non-adherence group (PRM < 0.8) had a lower risk of suicide (HR, 0.527, 95% CI, 0.447-0.620), an increased risk of NSSI (HR, 1.229, 95% CI, 1.088-1.388), and non-significant risk of attempted suicide compared with adherence group (PRM ≥ 0.8). For hypothesis 2, the lowest medication adherence (PRM < 0.2) was associated with increased risks of suicide attempt (HR, 1.614, 95% CI, 1.412-1.845), NSSI (HR, 1.873, 95% CI, 1.649-2.126), and a decreased risk of suicide (HR, 0.593, 95% CI, 0.490-0.719). The other non-adherence groups had lower risks for all three self-inflicted violence behaviors. The associations between medication adherence in continuous-variable and three outcomes were consistent with the categorical medication adherence results.
Almost no medication taken as prescribed was associated with an increased risk of suicide attempt and NSSI. However, medication adherence did not appear to prevent completed suicide. Besides, patients with moderate adherence had a lower incidence of suicide attempt and NSSI. These findings highlight the need for a more detailed portrayal of medication adherence and the need to be vigilant for suicide intent in schizophrenics with good medication adherence who may be overlooked previously.
Purpureocillium lilacinum, widely used as a commercial biocontrol agent for controlling plant-parasitic nematodes, is an emerging opportunistic pathogen in humans and is increasingly reported, ...especially among immunocompromised patients. We report a classic case of cutaneous mycosis caused by P. lilacinum. A 51-year-old Chinese woman who received tacrolimus and glucocorticoid therapy for 3 years for nephrotic syndrome experienced recurrent papules, pustules, and ulceration on her right ring finger and subcutaneous nodules on her forearm 6 months ago. A lesion biopsy on the right ring finger revealed multiple epithelioid granulomas in the dermis and fat layer containing slender, pigmented fungal hyphae. The fungal culture showed the growth of violet floccose colonies. Lactophenol cotton blue culture stain demonstrated brush-like phialides, with a swollen basal part attached to chains of conidia. Sequencing of the internal transcribed spacer regions of ribosomal DNA, alignment with GenBank, and use of a Basic Local Alignment Search Tool analysis led to the identification of P. lilacinum. Treatment with oral voriconazole was successful.
NiAl-LDHs with tunable acid-base sites were fabricated by hexamethylenetetramine(HMT) hydrolysis method, and acid-base sites were probed in synthesis of furfural diethyl acetal from furfural and ...ethanol. XRD, FT-IR, XPS, EXAFS, PALS, NH3-TPD, Pyridine-IR, ICP/AES and CHN element analysis were used to investigate the composition, structure, and origination of the acid-base activity sites of NiAl-LDHs. The result showed that nitrate intercalated LDH (marked as NiAl-NO3-LDH) and carbonate intercalated LDH (marked as NiAl-CO3-LDH) could be tunably fabricated under different synthetic pH. The acid-base sites of NiAl-CO3-LDH and NiAl-NO3-LDH presented significant difference. NiAl-NO3-LDH expressed preferable acid catalytic property with fine acid activity sites. However, NiAl-CO3-LDH presented inert activity in the acid catalysis reaction due to the absence of appropriate acid activity sites. Further investigations proved that the appearance of proper oxygen vacancy arising from low coordination Ni2+ in NiAl-NO3-LDH contributed to the establishment of Lewis acid sites. Accordingly, the intrinsic law of synthetic pH orienting the establishment of acid-base activity sites was revealed.
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•NiAl-NO3-LDH and NiAl-CO3-LDH were purposefully fabricated by HMT hydrolysis.•Proper acid-base activity sites were tunably established on NiAl-LDHs.•Acidic sites stemming from low coordination Ni2+ in NiAl-NO3-LDH were confirmed.•The inherent law of pH orienting the establishment of activity sites was revealed.
Comparing the priority order of different agricultural science and technology services adopted by cotton farmers and exploring the influencing factors of agricultural science and technology service ...adoption by cotton farmers from the perspective of farmer differentiation is significantly influential for high-quality agricultural development. We explore factors influencing the adoption of agricultural science and technology services by a cotton farmer from the perspective of farmer differentiation based on 335 research data in Xinjiang of China. The results show that cotton farmers adopted agricultural science and technology services in the following order: pest control technology, good seed technology, and precision sowing technology. Farm household fragmentation significantly affects the adoption of agricultural technology services by farm households. Gender and satisfaction with agricultural science and technology services were significantly influenced the adoption of agricultural science and technology services by the pure and part-time farmers; the variables of education level, planting area, and the number of household laborer was effected the adoption of agricultural science and technology services by the pure farmer. As such, organizations of agricultural science and technology service should develop personalized services according to the characteristics of cotton farmer endowments, improve the timeliness of agricultural science and technology services, and enhance service quality.
Microplastic pollution is widespread, affecting even the remotest places on Earth. However, observational data on microplastic deposition in deserts, which comprise 21% of the total land area, are ...relatively rare. The current study aims to address the knowledge gap in terms of microplastic distribution in Asian deserts. The Badain Jaran Desert in Central Asia is the second largest desert in China. We investigated microplastic distribution and deposition on dunes and lakes of this desert. Microplastics were extracted from surface sediments to determine their characteristics and polymer types by microscopic inspection and μ-FTIR. The abundance of microplastics (detection limit is approximately 40 μm) in the uninhabited area ranged from 0.7 ± 1.5 to 11.7 ± 15.5 items/kg, with an average of 6.0 ± 15.4 items/kg. Fragments and fibers accounted for 77% and 23% of the total microplastics, respectively. Epoxy resin (28%), polyethylene terephthalate (25%), phenoxy resin (25%), and polyamide (9%) were the main polymer components, whose sizes were concentrated at 50–200 μm. Back-trajectory modeling was then performed to explore the possible source direction of the microplastics. The results showed that the microplastics mainly originated from the populated areas southeast of the desert, indicating long-distance atmospheric transport and deposition in deserts. The desert-edge zone with some tourism activity contained more microplastics (8.2 ± 17.9 items/kg) than the non-tourism zone (0.9 ± 1.6 items/kg), indicating a potential contribution from tourism. The abundance in the non-tourism zone (0.9 items/kg) can be used as a reference for microplastic background values in the Central Asian deserts, as this value is critical for simulating and predicting global microplastic yields.
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•Investigating microplastic distribution & deposition in pristine Badain Jaran desert•Microplastic particles were predominantly fragments.•Microplastics mainly originated from populated areas by long-distance air transport.•Desert-edge zone with tourism contained more microplastics than non-tourism zone.•The data provide a background value of microplastic abundance in Central Asian desert.
Based on numerical experiments undertaken with nine climate models, the glacier equilibrium line altitudes (ELAs) in western China during the last glacial maximum (LGM) are investigated to deepen our ...understanding of the surface environment on the Tibetan Plateau. Relative to the preindustrial period, the summer surface air temperatures decrease by 4–8°C while the annual precipitation decreases by an average of 25% across the Tibetan Plateau during the LGM. Under the joint effects of reductions in summer temperature and annual precipitation, the LGM ELAs in western China are lowered by magnitudes that vary with regions. The ELAs in the southern margin and northwestern Tibetan Plateau decline by approximately 1100 m; the central hinterland, by 650–800 m; and the eastern part, by 550–800 m, with a downward trend from southwest to northeast. The reduction in ELAs is no more than 650 m in the Tian Shan Mountains within China and approximately 500–600 m in the Qilian Mountains and Altai Mountains. The high-resolution models to reproduce the low values of no more than 500 m in ELA reductions in the central Tibetan Plateau, which are consistent with the proxy records from glacier remains. The accumulation zones of the Tibetan Plateau glaciers are mainly located in the marginal mountains during the LGM and have areas 2–5 times larger than those of the modern glaciers but still do not reach the central part.
Saffron spice, as a high value-added but not high-tech processed agricultural product, is easily faked and mislabeled its quality grade and origin for higher market profits and competitiveness. In ...this work, an analytical strategy combining chemical composition analysis and stable isotope ratio analysis of saffron spices was explored for verifying their quality and origin authenticity in China market. The crocins contents and stable isotope ratios of 70 saffron spice samples collected from five provinces of China and 95 imported products from Iran and Spain were determined together. The contents of crocins may be effective as the indexes of their quality evaluation but not for origin traceability. Relatively, regional difference of stable isotope ratios is significant (p < 0.05) between different origins. Partial least-squares discriminant analysis (PLS-DA) based on chemical compositions and stable isotope ratios of 165 saffron spice samples can identify imported products from Iran and Spain with the accuracies of 98.5 % and 100 %, but still may mis-discriminate samples from Henan and Xinjiang province of China as Iran products, which was further solved by PLS-DA of products from these origins. This strategy is promising as an effective tool for combating commercial frauds and ensuring the authenticity of saffron spice in China market.
•Quality assessment of saffron cannot effectively verify its geographical value.•Stable isotope ratios can be as the geographical indicators of saffron spice.•Modeling of stable isotope ratios aims to identify imported and domestic products.•PLS-DA discriminates the origin of saffron spice in China market with 90 % accuracy.•This strategy is able to ensure the origin authenticity of saffron spice in global trade.
Paeonol, an active compound isolated from the radix of
, has been shown to have anti-atherosclerosis effects by regulating blood cells' function and protecting vascular cells injury. Besides, ...emerging evidences has proven that exosomes might play a pivotal role in intercellular communication by transmiting proteins and microRNAs from cell to cell. However, the relationship between monocytes-derived exosomal microRNA-223 and vascular inflammation injury along with paeonol' effects are still not clear.
Our study aimed to explain whether paeonol's protective effect on inflammatory response is related to the regulation of exosomal microRNA-223 in the VECs.
ApoE
mice were fed with high fat diet to replicate the AS model. HE staining and immunohistochemistry was used to detect inflammatory response of aorta. The expression of IL-1β and IL-6 were detected by ELISA. Western blot was used to detect the expression of STAT3, pSTAT3, ICAM-1 and VCAM-1. qRT-PCR was used to detect miR-223 expression. Exosomes were extracted from THP-1 cells by differential centrifugation and observed by transmission electron microscope. Observation of exosomes uptake into HUVECs was realized by laser microscopy. miR-223 target gene was detected by double luciferase gene report test.
experiments confirmed that paeonol restricted atherosclerosis development and increased miR-223 expression, inhibited STAT3 pathway in ApoE
mice.
, miR-223 showed robust presence in THP-1 cells and undetectable in HUVECs. And we had observed that miR-223 could be internalized from THP-1 cells into HUVECs taking exosomes as a carrier. Paeonol obviously increased miR-223 expression in co-cultured HUVECs and exosomes in concentration dependent manner, compared to LPS group. In addition, paeonol relieved inflammatory secretion, adhesion and STAT3 expression in HUVECs, which could be inverted after miR-223 inhibitor transfection into THP-1 cells.
Paeonol could increase the expression of miR-223 in THP-1 derived exosomes and in HUVECs after uptake of exosomes, whereas decrease the expression of STAT3, p-STAT3 in HUVECs. Ultimately paeonol decreased the expression of IL-1β, IL-6, ICAM-1, VCAM-1 in HUVECs and alleviated adhesion of THP-1 cells to HUVECs.
Rationale: Silicosis is a severe occupational lung disease. Current treatments for silicosis have highly limited availability (i.e., lung transplantation) or, do not effectively prolong patient ...survival time (i.e., lung lavage). There is thus an urgent clinical need for effective drugs to retard the progression of silicosis. Methods: To systematically characterize the molecular changes associated with silicosis and to discover potential therapeutic targets, we conducted a transcriptomics analysis of human lung tissues acquired during transplantation, which was integrated with transcriptomics and metabolomics analyses of silicosis mouse lungs. The results from the multi-omics analyses were then verified by qPCR, western blot, and immunohistochemistry. The effect of Ramatroban on the progression of silicosis was evaluated in a silica-induced mouse model. Results: Wide metabolic alterations were found in lungs from both human patients and mice with silicosis. Targeted metabolite quantification and validation of expression of their synthases revealed that arachidonic acid (AA) pathway metabolites, prostaglandin D2 (PGD2) and thromboxane A2 (TXA2), were significantly up-regulated in silicosis lungs. We further examined the effect of Ramatroban, a clinical antagonist of both PGD2 and TXA2 receptors, on treating silicosis using a mouse model. The results showed that Ramatroban significantly alleviated silica-induced pulmonary inflammation, fibrosis, and cardiopulmonary dysfunction compared with the control group. Conclusion: Our results revealed the importance of AA metabolic reprogramming, especially PGD2 and TXA2 in the progression of silicosis. By blocking the receptors of these two prostanoids, Ramatroban may be a novel potential therapeutic drug to inhibit the progression of silicosis.
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