New Sight of Renal Toxicity Caused by UV-Aged Polystyrene Nanoplastics: Induced Ferroptosis via Adsorption of Transferrin.

Secondary nanoplastics (NPs) caused by degradation and aging due to environmental factors are the main source of human exposure, and alterations in the physicochemical and biological properties of NPs induced by environmental factors cannot be overlooked. In this study, pristine polystyrene (PS) NPs to obtain ultraviolet (UV)-aged PS NPs (aPS NPs) as secondary NPs is artificially aged. In a mouse oral exposure model, the nephrotoxicity of PS NPs and aPS NPs is compared, and the results showed that aPS NPs exposure induced more serious destruction of kidney tissue structure and function, along with characteristic changes in ferroptosis. Subsequent in vitro experiments revealed that aPS NPs-induced cell death in human renal tubular epithelial cells involved ferroptosis, which is supported by the use of ferrostatin-1, a ferroptosis inhibitor. Notably, it is discovered that aPS NPs can enhance the binding of serum transferrin (TF) to its receptor on the cell membrane by forming an aPS-TF complex, leading to an increase in intracellular Fe2+ and then exacerbation of oxidative stress and lipid peroxidation, which render cells more sensitive to ferroptosis. These findings indicated that UV irradiation can alter the physicochemical and biological properties of NPs, enhancing their kidney biological toxicity risk by inducing ferroptosis.

Lipidomics Reveals the Effects of Detergents on Skin Surface Lipids in Young Adults.

BACKGROUND: Detergent is a chemical product commonly used in people's daily life. Contact with detergent solutions can damage the human skin barrier and cause skin diseases. Skin surface lipids (SSLs) play a decisive role in skin barrier function. This study aimed to observe the changes of SSLs in young adults after exposure to detergent solutions to explore the underlying mechanism of skin barrier function damage. METHODS: A self-controlled study on youth adults was conducted in Zhengzhou, China, in November 2020. The study lasted for a total of 1 week, and skin barrier function was assessed by trans-epidermal water loss (TEWL) values. The changes of SSLs before and after exposure to the detergent with subjects were measured using ultra-performance liquid chromatography quadrupole time of flight mass spectrometry. RESULTS: The skin barrier function of subjects' hands was impaired after exposure to detergent (TEWL value increased, p < 0.001). A total of 520 SSLs were detected, divided into 6 main categories. The average relative abundance of these 6 major lipids decreased after exposure. Sphingolipids (mainly ceramides), free fatty acids (mainly long-chain fatty acids), cholesterol lipids, and glycerophospholipids are the most severely damaged lipids. CONCLUSION: Detergent solutions can damage the skin barrier function and SSLs of young hands; interventions targeting SSLs to eliminate detergent damage to human skin may be of value.

The Brachypodium distachyon DREB transcription factor BdDREB-39 confers oxidative stress tolerance in transgenic tobacco.

Key message BdDREB-39 is a DREB/CBF transcription factor, localized in the nucleus with transactivation activity, and BdDREB-39-overexpressing transgenic yeasts and tobacco enhanced the tolerance to oxidative stress.Abstract The DREB/CBF transcription factors are generally recognized to play an important factor in plant growth, development and response to various abiotic stresses. However, the mechanism of DREB/CBFs in oxidative stress response is largely unknown. This study isolated a DREB/CBF gene BdDREB-39 from Brachypodium distachyon (B. distachyon). Multiple sequence alignment and phylogenetic analysis showed that BdDREB-39 was closely related to the DREB proteins of oats, barley, wheat and rye and therefore its study can provide a reference for the excavation and genetic improvement of BdDREB-39 or its homologs in its closely related species. The transcript levels of BdDREB-39 were significantly up-regulated under H2O2 stress. BdDREB-39 was localised in the nucleus and functioned as a transcriptional activator. Overexpression of BdDREB-39 enhanced H2O2 tolerance in yeast. Transgenic tobaccos with BdDREB-39 had higher germination rates, longer root, better growth status, lesser reactive oxygen species (ROS) and malondialdehyde (MDA), and higher superoxide dismutase (SOD) and peroxidase (POD) activities than wild type (WT). The expression levels of ROS-related and stress-related genes were improved by BdDREB-39. In summary, these results revealed that BdDREB-39 can improve the viability of tobacco by regulating the expression of ROS and stress-related genes, allowing transgenic tobacco to accumulate lower levels of ROS and reducing the damage caused by ROS to cells. The BdDREB-39 gene has the potential for developing plant varieties tolerant to stress.

Determination of the diagnostic accuracy of nanopore sequencing using bronchoalveolar lavage fluid samples from patients with sputum-scarce pulmonary tuberculosis.

PURPOSE: The early and efficient diagnosis of patients suspected of having pulmonary tuberculosis (PTB) remains challenging. This study aimed to evaluate the accuracy of nanopore sequencing for PTB diagnosis using bronchoalveolar lavage fluid (BALF) samples and compared it with other techniques such as acid-fast bacilli smear, culture, Xpert MTB/RIF, and CapitalBio Mycobacterium reverse transcription-polymerase chain reaction (MTB RT-PCR). METHODS: We retrospectively analyzed the clinical data of 195 patients with suspected PTB who were admitted to our hospital. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC) of these assays were calculated and compared. RESULTS: The overall sensitivity, specificity, PPV, NPV, and AUC of nanopore sequencing were 90.70%, 84.85%, 92.13%, 82.35%, and 0.88; those of acid-fast bacilli smear were 12.40%, 98.48%, 94.12%, 36.52%, and 0.55; those of culture were 36.43%, 100%, 100%, 44.59%, and 0.68; those of Xpert MTB/RIF were 41.09%, 100%, 100%, 46.48%, and 0.71; and those of CapitalBio MTB RT-PCR were 34.88%, 98.48%, 97.83%, 43.62%, and 0.67, respectively. CONCLUSION: The nanopore sequencing assay using BALF samples showed the best diagnostic accuracy for sputum-scarce PTB. Moreover, it can improve the clinical diagnosis of PTB.

Cryo-EM structure of the Smc5/6 holo-complex.

The Smc5/6 complex plays an essential role in the resolution of recombination intermediates formed during mitosis or meiosis, or as a result of the cellular response to replication stress. It also functions as a restriction factor preventing viral replication. Here, we report the cryogenic EM (cryo-EM) structure of the six-subunit budding yeast Smc5/6 holo-complex, reconstituted from recombinant proteins expressed in insect cells - providing both an architectural overview of the entire complex and an understanding of how the Nse1/3/4 subcomplex binds to the hetero-dimeric SMC protein core. In addition, we demonstrate that a region within the head domain of Smc5, equivalent to the 'W-loop' of Smc4 or 'F-loop' of Smc1, mediates an important interaction with Nse1. Notably, mutations that alter the surface-charge profile of the region of Nse1 which accepts the Smc5-loop, lead to a slow-growth phenotype and a global reduction in the chromatin-associated fraction of the Smc5/6 complex, as judged by single molecule localisation microscopy experiments in live yeast. Moreover, when taken together, our data indicates functional equivalence between the structurally unrelated KITE and HAWK accessory subunits associated with SMC complexes.

Associations between maternal serum neonicotinoid pesticide exposure during pregnancy and newborn telomere length: Effect modification by sampling season.

BACKGROUND: An increasing amount of evidence suggests that telomere length (TL) at birth can predict lifespan and is associated with chronic diseases later in life, but newborn TL may be affected by environmental pollutants. Neonicotinoids (NEOs) are widely used worldwide, and despite an increasing number of studies showing that they may have adverse effects on birth in mammals and even humans, few studies have examined the effect of NEO exposure on newborn TLs. OBJECTIVE: To investigate the effects of prenatal exposure to NEOs and the interactions between NEOs and sampling season on newborn TL. METHODS: We conducted a prospective cohort study of 500 mother-newborn pairs from the Guangxi Zhuang Birth Cohort. Ultraperformance liquid chromatographymass spectrometry was used to detect ten NEOs in maternal serum, and fluorescence quantitative PCR was used to estimate the newborn TL. A generalized linear model (GLM) was used to evaluate the relationships between individual NEO exposures and TLs , and quantile g-computation (Qgcomp) model and Bayesian kernel machine regression (BKMR) model were used to evaluate the combined effect of mixtures of components. RESULTS: The results of the GLM showed that compared with maternal TMX levels < LOD, maternal TMX levels < median were negatively correlated with newborn TL (-6.93%, 95% CI%: -11.92%, -1.66%), and the decrease in newborn TL was more pronounced in girls (-9.60%, 95% CI: -16.84%, -1.72%). Moreover, different kinds of maternal NEO exposure had different effects on newborn TL in different sampling seasons, and the effect was statistically significant in all seasons except in autumn. Mixed exposure analysis revealed a potential positive trend between NEOs and newborn TL, but the association was not statistically significant. CONCLUSION: Prenatal exposure to TMX may shorten newborn TL, and this effect is more pronounced among female newborns. Furthermore, the relationship between NEO exposure and TL may be modified by the sampling season.

Associations of prenatal exposure to per- and polyfluoroalkyl substances and fetal sex hormones in the Guangxi Zhuang Birth Cohort Study: Greater effect of long-chain PFAS.

Fetal sex hormone homeostasis disruption could lead to reproductive and developmental abnormalities. However, previous studies have reported inconsistent findings regarding the association of maternal per- and polyfluoroalkyl substances (PFAS) exposure with fetal sex hormone levels. A total of 277 mother-infant pairs from the Guangxi Zhuang Birth Cohort Study between 2015 and 2019 were selected. We quantified nine PFAS in maternal serum in early pregnancy, and detected three sex hormones, namely, estradiol (E2), progesterone (P4) and testosterone (TT), in cord blood. The generalized linear model (GLM) and Bayesian kernel machine regression (BKMR) model were used for single- and multiple-exposure analyses, respectively. In the GLM, there was no significant association between an individual PFAS and any hormone level or the E2/TT ratio, but a negative association between perfluorododecanoic acid (PFDoA) exposure and P4 levels in female infants was observed after stratification by sex. In the BKMR, a mixture of nine PFAS was positively associated with E2 levels and the E2/TT ratio, with the same main contributors, i.e., perfluoroundecanoic acid (PFUnA). And PFAS mixtures were not associated with P4 or TT levels. After stratification by infant sex, positive associations of PFAS mixtures with E2 levels and the E2/TT ratio were observed only in male infants, with the same main contributors, i.e., PFUnA. There was a positive association between PFAS mixtures and P4 levels in male infants, in which PFUnA was the main contributor; but a reverse association between PFAS mixtures and P4 levels in female infants, in which PFDoA was the main contributor. This study suggested that prenatal exposure to PFAS mixtures is associated with fetal sex hormones, and long-chain PFAS may play an important role in this association. Furthermore, sex differences in the association of maternal PFAS exposure with E2 and P4 levels need additional attention.

Material Composition Characteristics of Aspergillus cristatus under High Salt Stress through LC-MS Metabolomics.

Aspergillus cristatus is a crucial edible fungus used in tea fermentation. In the industrial fermentation process, the fungus experiences a low to high osmotic pressure environment. To explore the law of material metabolism changes during osmotic pressure changes, NaCl was used here to construct different osmotic pressure environments. Liquid chromatography-mass spectrometry (LC-MS) combined with multivariate analysis was performed to analyze the distribution and composition of A. cristatus under different salt concentrations. At the same time, the in vitro antioxidant activity was evaluated. The LC-MS metabolomics analysis revealed significant differences between three A. cristatus mycelium samples grown on media with and without NaCl concentrations of 8% and 18%. The contents of gibberellin A3, A124, and prostaglandin A2 related to mycelial growth and those of arabitol and fructose-1,6-diphosphate related to osmotic pressure regulation were significantly reduced at high NaCl concentrations. The biosynthesis of energy-related pantothenol and pantothenic acid and antagonism-related fluvastatin, aflatoxin, and alternariol significantly increased at high NaCl concentrations. Several antioxidant capacities of A. cristatus mycelia were directly related to osmotic pressure and exhibited a significant downward trend with an increase in environmental osmotic pressure. The aforementioned results indicate that A. cristatus adapts to changes in salt concentration by adjusting their metabolite synthesis. At the same time, a unique set of strategies was developed to cope with high salt stress, including growth restriction, osmotic pressure balance, oxidative stress response, antioxidant defense, and survival competition.

Image-based vegetation analysis of desertified area by using a combination of ImageJ and Photoshop software.

Fractional vegetation cover (FVC) is a crucial indicator to estimate degradation and desertification for grasslands. However, traditional small-scale FVC analysis methods, such as visual estimation and point-sampling, are cumbersome and imprecise. Innovative methods like image-based FVC analysis methods, while accurate, face challenges such as complex analytical procedures and the necessary training for operations. Therefore, in this study, a combined application of ImageJ and Photoshop was employed to achieve a more effective analysis of FVC values in desertification areas. Our results showed that the FVC results obtained by combination of Photoshop and ImageJ were dependable and precise (R2 > 0.98), demonstrating equivalency to results obtained through either visual estimation or Photoshop-based methods. Furthermore, even in the face of background interference and varied shooting angles, the combination of ImageJ and Photoshop software was still able to maintain a low error rate when analyzing FVC values (average error rate = - 2.6%). In conclusion, the imaged-based combined FVC analysis method employed in our research was an effective, precise, and efficient technique for analyzing small-scale FVC, promising substantial improvement over conventional methods.

Enhanced hepatic metabolic perturbation of polystyrene nanoplastics by UV irradiation-induced hydroxyl radical generation.

The environmental behavior of and risks associated with nanoplastics (NPs) have attracted considerable attention. However, compared to pristine NPs, environmental factors such as ultraviolet (UV) irradiation that lead to changes in the toxicity of NPs have rarely been studied. We evaluated the changes in morphology and physicochemical properties of polystyrene (PS) NPs before and after UV irradiation, and compared their hepatotoxicity in mice. The results showed that UV irradiation caused particle size reduction and increased the carbonyl index (CI) and negative charge on the particle surface. UV-aged PS NPs (aPS NPs) could induce the generation of hydroxyl radicals (·OH), but also further promoted the generation of ·OH in the Fenton reaction system. Hepatic pathological damage was more severe in mice exposed to aPS NPs, accompanied by a large number of vacuoles and hepatocyte balloon-like changes and more marked perturbations in blood glucose and serum lipoprotein, alanine aminotransferase and aspartate aminotransferase levels. In addition, exposure to PS NPs and aPS NPs, especially aPS NPs, triggered oxidative stress and significantly damaged the antioxidant capacity of mice liver. Compared with PS NPs, exposure to aPS NPs increased the number of altered metabolites in hepatic and corresponding metabolic pathways, especially glutathione metabolism. Our research suggests that UV irradiation can disrupt the redox balance in organisms by promoting the production of ·OH, enhancing PS NPs-induced liver damage and metabolic disorders. This study will help us understand the health risks of NPs and to avoid underestimation of the risks of NPs in nature.

Nse5/6 is a negative regulator of the ATPase activity of the Smc5/6 complex.

The multi-component Smc5/6 complex plays a critical role in the resolution of recombination intermediates formed during mitosis and meiosis, and in the cellular response to replication stress. Using recombinant proteins, we have reconstituted a series of defined Saccharomyces cerevisiae Smc5/6 complexes, visualised them by negative stain electron microscopy, and tested their ability to function as an ATPase. We find that only the six protein 'holo-complex' is capable of turning over ATP and that its activity is significantly increased by the addition of double-stranded DNA to reaction mixes. Furthermore, stimulation is wholly dependent on functional ATP-binding pockets in both Smc5 and Smc6. Importantly, we demonstrate that budding yeast Nse5/6 acts as a negative regulator of Smc5/6 ATPase activity, binding to the head-end of the complex to suppress turnover, irrespective of the DNA-bound status of the complex.

PM2.5 induces alterations in gene expression profile of platelet-derived extracellular vesicles and mediates cardiovascular injury in rats.

Platelet-derived extracellular vesicles (P-EVs), as the most abundant vesicles in blood, have been proven to play cardinal roles in cardiovascular injury. RNAs (especially miRNAs) carried by P-EVs can be transferred to the receptor, which plays a critical role in regulating vascular endothelial function. PM2.5 is one of the most well-known risk factors that cause cardiovascular disease. Therefore, the objective of the current study was to explore whether exposure to PM2.5 would alter the gene expression profile of P-EVs, and to further elucidate the role of RNAs (especially miRNAs) carried by P-EVs in cardiovascular injury induced by PM2.5 exposure. P-EVs were isolated from the platelet-rich plasma which was exposed and unexposed to PM2.5, and the differentially expressed target genes were evaluated using whole-transcriptome gene sequencing. Rats were treated with P-EVs under different exposure conditions (a protein concentration of 50 µg/mL) and an equal volume of normal saline. The pathological damage of the thoracic aorta and cardiac tissue was evaluated and the coagulation function of the rats was detected. The differentially expressed genes were shown to be mainly concentrated in inflammation, angiogenesis, and apoptosis-related pathways. Moreover, P-EVs extracted from PM2.5-exposed plasma had the potential to trigger an inflammatory response, impair vascular endothelial function, disrupt the normal coagulation process, and promote a prothrombotic state. Our study indicated that PM2.5 induces cardiovascular injury in rats by interfering with the gene expression of P-EVs. It will provide new targets for studying the mechanism involved in PM2.5-induced cardiovascular injury.

Short term exposure to polystyrene nanoplastics in mice evokes self-regulation of glycolipid metabolism.

With the detection of nano-plastics (NPs) in daily essentials and drinking water, the potential harm of NPs to human health has become the focus of global attention. Studies have shown that long term exposure to NPs can lead to disorders of glucose and lipid metabolism in organisms, while the effects of short term exposure are rarely reported. Moreover, environmental factors cause the aging of NPs, and it is unclear whether this has an effect on their toxicity. In this study, we use 100 nm polystyrene (PS) NPs and ultraviolet (UV) aging PS (aPS) NPs to gavage mice for 7 days at an exposure dose of 50 mg/kg/day. To evaluate the effects of exposure on mice hepatic glucose lipid metabolism, we performed blood biochemical, pathological and metabolomic analyses. The results showed that exposure to PS NPs and aPS NPs increased serum glucose, disrupted serum lipoprotein levels, and up-regulated the expression levels of phosphatidylinositol 3-kinase (PI3K)/ phosphoprotein kinase B (p-AKT)/Glucose transporter 4 (GLUT4) proteins in the glucose metabolism pathway. The expression levels of key proteins sterol regulatory element binding protein-1 (SREBP-1)/peroxisome proliferator-activated receptor-γ (PPARγ)/adipose triglyceride lipase (ATGL) in the lipid metabolism signaling pathway were significantly increased. These findings suggest that short term exposure to PS NPs and aPS NPs induces glycolipid metabolism disturbance in mice, which may subsequently awaken the mice to self-regulate the serum levels of various lipoproteins and the expression of related key proteins. Compared with PS NPs, the aPS NPs interfered more strongly with glucose metabolism, and the corresponding self-regulation in mice was also more obvious. These findings not only provide a basis for environmental factors to increase the health risk of NPs but also provided a reference for the selection of test substances for further studies on the toxicity of NPs.

Effects of several polymeric materials on the improvement of the sandy soil under rainfall simulation.

Poor cementation between soil particles is a fundamental cause of soil erosion and desertification. In recent decades, many polymers have been used to cement soil particles and improve the physical and chemical properties of soils. The contributions of polymers with different structures and functional groups to soil improvement vary considerably. In this study, a mixture comprising polyacrylamide (PAM), sodium polyacrylate (PAAS), hydroxypropyl methylcellulose (HPMC), and polyvinyl alcohol (PVA) was investigated to meet the requirements of soil water retention, erosion resistance, and plant growth. The results showed that the time required for the modified soil to reach drought conditions was extended by 4-7 days. The PAM/HPMC, PAM/PVA and PAM/PAAS experimental groups reduced the erosion rate by 99.57%, 98.3% and 96.38%, respectively, compared to that of the control group. The belowground plant biomass was significantly increased by PAM/HPMC, PAM/PAAS, and PAM/PVA, with increases of 115.92%, 145.23%, and 205.67%, respectively. HPMC contributed more to the soil erosion resistance and water-holding capacity, PAAS improved the soil porosity substantially, and PVA significantly increased the plant biomass. The rigid structures of the polymer chains enhanced the structural stability of the soil, and the hydrophilic functional groups increased the hydrophilicity of the amended soil. This study indicates different polymers that may be used to improve soil properties.

Acoustic radiation force on a long cylinder, and potential sound transduction by tomato trichomes.

Acoustic transduction by plants has been proposed as a mechanism to enable just-in-time up-regulation of metabolically expensive defensive compounds. Although the mechanisms by which this "hearing" occurs are unknown, mechanosensation by elongated plant hair cells known as trichomes is suspected. To evaluate this possibility, we developed a theoretical model to evaluate the acoustic radiation force that an elongated cylinder can receive in response to sounds emitted by animals, including insect herbivores, and applied it to the long, cylindrical stem trichomes of the tomato plant Solanum lycopersicum. Based on perturbation theory and validated by finite element simulations, the model quantifies the effects of viscosity and frequency on this acoustic radiation force. Results suggest that acoustic emissions from certain animals, including insect herbivores, may produce acoustic radiation force sufficient to trigger stretch-activated ion channels.

A novel insight into mechanism of derangement of coagulation balance: interactions of quantum dots with coagulation-related proteins.

BACKGROUND: Quantum dots (QDs) have gained increased attention for their extensive biomedical and electronic products applications. Due to the high priority of QDs in contacting the circulatory system, understanding the hemocompatibility of QDs is one of the most important aspects for their biosafety evaluation. Thus far, the effect of QDs on coagulation balance haven't been fully understood, and limited studies also have yet elucidated the potential mechanism from the perspective of interaction of QDs with coagulation-related proteins. RESULTS: QDs induced the derangement of coagulation balance by prolonging the activated partial thromboplastin time and prothrombin time as well as changing the expression levels of coagulation and fibrinolytic factors. The contact of QDs with PTM (prothrombin), PLG (plasminogen) and FIB (fibrinogen) which are primary coagulation-related proteins in the coagulation and fibrinolysis systems formed QDs-protein conjugates through hydrogen-bonding and hydrophobic interaction. The affinity of proteins with QDs followed the order of PTM > PLG > FIB, and was larger with CdTe/ZnS QDs than CdTe QDs. Binding with QDs not only induced static fluorescence quenching of PTM, PLG and FIB, but also altered their conformational structures. The binding of QDs to the active sites of PTM, PLG and FIB may promote the activation of proteins, thus interfering the hemostasis and fibrinolysis processes. CONCLUSIONS: The interactions of QDs with PTM, PLG and FIB may be key contributors for interference of coagulation balance, that is helpful to achieve a reliable and comprehensive evaluation on the potential biological influence of QDs from the molecular level.

Safety and tolerance assessment of milk fat globule membrane-enriched infant formulas in healthy term Chinese infants: a randomised multicenter controlled trial.

BACKGROUND: Milk fat globule membrane (MFGM), natural to breast milk, is essential for neonatal development, but lacking from standard infant formulas. OBJECTIVES: To evaluate the safety and tolerability of MFGM supplementation in formula for infants 0 to 12 months. METHODS: In a prospective, multicentre, double-blind, randomized trial, healthy term infants were randomized to a standard formula (SF, n = 104) or an MFGM-enriched formula (MF, n = 108) for 6 months and a corresponding follow-on formula until 12 months. Exclusively breast-fed infants (n = 206) were recruited as the reference group (BFR). Tolerance and safety events were recorded continuously. Anthropometric measurements were assessed at enrolment, 42 days and 4, 6, 8 and 12 months. RESULTS: Infants (n = 375) completed the study with average dropout of < 20%. Stool frequency, color, and consistency between SF and MF were not significantly different throughout, except the incidence of loose stools in MF at 6 months being lower than for SF (odds ratio 0.216, P < 0.05) and the frequency of green-colored stools at 12 months being higher in MF (CI 95%, odds ratio 8.92, P < 0.05). The BFR had a higher frequency of golden stools and lower rate of green stools (4-6 months) than the two formula-fed groups (P < 0.05). SF displayed more diarrhoea (4.8%) than MF (1%) and BFR (1%) at the 8-month visit (P < 0.05). BFR (0-1%) had significantly less (P < 0.05) lower respiratory infections than MF (4.6-6.5%) and SF (2.9-5.8%) at 6- and 8-months, respectively. Formula intake, frequency of spit-up/vomiting or poor sleep were similar between SF and MF. Growth rate (g/day) was similar at 4, 6, 8 and 12 months between the 3 groups, but growth rate for BFR was significantly higher than for SF and MF at 42 days (95% CI, P = 0.001). CONCLUSIONS: MFGM-enriched formula was safe and well-tolerated in healthy term infants between 0 and 12 months, and total incidences of adverse events were similar to that for the SF group. A few differences in formula tolerance were observed, however these differences were not in any way related to poor growth.

Traditional use and safety evaluation of combination Traditional Chinese Medicine in European registration: with XiaoYao Tablets as an example.

Mental health disorders such as stress, anxiety, depression and insomnia caused by COVID-19 have attracted worldwide attention. Traditional Chinese medicines (TCMs) have been proven to be a safe and effective option for treating mental health disorders. Recently, after assessing its efficacy and safety fully, the Netherlands Medicines Evaluation Board approved XiaoYao Tablets as a traditional herbal medicinal product (THMP), indicated for an alternative self-care for patients in Europe to relieve the symptoms of mental stress and exhaustion. Despite the fact that TCMs have gradually become one of the therapeutic choices worldwide, to-date, only a few TCMs have been successfully registered in the European Union (EU) as THMPs, and XiaoYao Tablets is the first successfully registered combination TCM from China. In this article, traditional use efficacy and clinical safety of XiaoYao Tablets in the treatment of mental health disorders were summarized and analyzed from the perspective of traditional use registration (TUR). Additionally a safety evolution pathway of combination TCMs was established. This article will not only seek to enhance our understanding about traditional use efficacy and clinical safety of XiaoYao Tablets, but also summarize the experience of XiaoYao Tablets as the first successfully registered combination TCM from China, which could serve as role model for the others to overcome registration difficulties in the EU.

Diversity of transcription activator-like effectors and pathogenicity in strains of Xanthomonas oryzae pv. oryzicola from Yunnan.

The present study aimed to evaluate transcriptional activator-like effector (TALE) genes in 86 Xanthomonas oryzae pv. oryzicola strains collected from 8 rice-growing regions in Yunnan, and to examine the relationship between TALE genotypes and virulence in 6 differential rice lines. Besides, the geographical areas, distribution of these genotypes were studied in detail. Genetic diversity was analyzed through the number and size of putative TALE genes based on TALE gene avrXa3 as a probe. We found that X. oryzae pv. oryzicola strains consist of variable number (13-27) of avrXa3-hybridizing fragments (putative TALE genes). Test strains were classified into 8 genotypes (G1-G8) with major genotypes G3 and G7 widely distributed in Yunnan. Pathogenicity of X. oryzae pv. oryzicola was evaluated by inoculating 6 differential rice lines with a single resistance gene into 9 pathotypes clusters (I-IX), the dominant Genotypes G3 and G7 consist of pathotypes I, II, and IV. Furthermore, we also detected the known TALE target genes expression in susceptible rice cultivar (cv. nipponbare) after inoculating 8 genotypes-representative X. oryzae pv. oryzicola strain. Correlation between the numbers of putative TALE genes of X. oryzae pv. oryzicola and relevant target genes in nipponbare confirmed up-regulation. Altogether, this study has given insights into the population structure of X. oryzae pv. oryzicola that may inform strategies to control BLS in rice.

Long noncoding RNA NEAT1 promotes tumorigenesis in H. pylori gastric cancer by sponging miR-30a to regulate COX-2/BCL9 pathway.

BACKGROUND: Helicobacter pylori (H. pylori) is a carcinogenic factor for gastric cancer. Our previous study demonstrated that H. pylori decreased the expression of micro-RNA (miRNA)-30a to promote the tumorigenesis of gastric cancer. However, the upstream regulatory molecules of miR-30a are not well elucidated. In this study, we found the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) may sponge miR-30a to regulate COX-2/BCL9 pathway. METHODS: The expression of NEAT1 was detected in gastric cancer tissues and tumor-adjacent tissues by fluorescence in situ hybridization (FISH) analysis and RT-qPCR. LncRNA-miRNA interaction networks were constructed using the RNAhybrid and starBase v.2.0. and then validated using a dual-luciferase reporter assay. The effects of NEAT1 dysregulation on the proliferative, migratory, and invasive abilities of H. pylori filtrate-infected gastric cancer cells were observed by cell counting kit-8 (CCK-8), colony formation, wound healing test, and transwell assays. Western blot and RT-qPCR were performed to detect protein and RNA expression. Immunohistochemistry (IHC) was carried out to analyze the localization and expression of COX-2 and BCL9. RESULTS: FISH and RT-qPCR demonstrated that the expression of NEAT1 was up-regulated in gastric cancer tissues, especially in H. pylori-infected gastric cancer tissues, and the expression of NEAT1 was negatively correlated with miR-30a (miR-30a-3p and miR-30a-5p). The upregulation of NEAT1 enhanced proliferation, migration, and invasion of H. pylori filtrate-infected gastric cancer cells, while the downregulation of NEAT1 decreased these abilities, and miR-30a could reverse the effect of NEAT1 on these abilities. The dual-luciferase reporter assay identified that NEAT1 directly targeted miR-30a (miR-30a-3p and miR-30a-5p). Because miR-30a (miR-30a-3p and miR-30a-5p) negatively regulates the expression of downstream COX-2 and BCL9, NEAT1 was identified to upregulate indirectly the expression of COX-2 and BCL9. IHC showed that the expression of COX-2 and BCL9 was increased in H. pylori gastric cancer tissues. CONCLUSION: The study demonstrated that lncRNA NEAT1 may act as a promoter of tumorigenesis in H. pylori gastric cancer, by sponging miR-30a (miR-30a-3p and miR-30a-5p) to regulate the COX-2/BCL9 pathway.