Exploring the pharmacological mechanism of Xianlingubao against diabetic osteoporosis based on network pharmacology and molecular docking: An observational study.

Xianlinggubao formula (XLGB), is a traditional Chinese compound Medicine that has been extensively used in osteoarthritis and aseptic osteonecrosis, but its curative effect on diabetic osteoporosis (DOP) and its pharmacological mechanisms remains not clear. The aim of the present study was to investigate the possible mechanism of drug repurposing of XLGB in DOP therapy. We acquired XLGB active compounds from the traditional Chinese medicine systems pharmacology and traditional Chinese medicines integrated databases and discovered potential targets for these compounds by conducting target fishing using the traditional Chinese medicine systems pharmacology and Swiss Target Prediction databases. Gene Cards and Online Mendelian Inheritance in Man® database were used to identify the DOP targets. Overlapping related targets between XLGB and DOP was selected to build a protein-protein interaction network. Next, the Metascape database was utilized to enrich the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. In addition, Auto-Dock Vina software was used to verify drug and target binding. In total, 48 hub targets were obtained as the candidate targets responsible for DOP therapy. The anti-DOP effect mediated by XLGB was primarily centralized on the advanced glycation end products (AGEs)-receptor for AGE signaling pathway in diabetic complications and osteoclast differentiation. In addition, AKT serine/threonine kinase 1, tumor necrosis factor, Interleukin-6, vascular endothelial growth factor A and peroxisome proliferator activated receptor gamma, which were considered as potential therapeutic targets. Furthermore, molecular docking results confirm the credibility of the predicted therapeutic targets. This study elucidates that XLGB may through regulating AGEs formation and osteoclast differentiation as well as angiogenesis and adipogenesis against DOP. And this study provides new promising points to find the exact regulatory mechanisms of XLGB mediated anti-DOP effect.

High-precision early warning system for rice cadmium accumulation risk assessment.

Rapid global industrialization has resulted in widespread cadmium contamination in agricultural soils and products. A considerable proportion of rice consumers are exposed to Cd levels above the provisional safe intake limit, raising widespread environmental concerns on risk management. Therefore, a generalized approach is urgently needed to enable correct evaluation and early warning of cadmium contaminants in rice products. Combining big data and computer science together, this study developed a system named "SMART Cd Early Warning", which integrated 4 modules including genotype-to-phenotype (G2P) modelling, high-throughput sequencing, G2P prediction and rice Cd contamination risk assessment, for rice cadmium accumulation early warning. This system can rapidly assess the risk of rice cadmium accumulation by genotyping leaves at seeding stage. The parameters including statistical methods, population size, training population-testing population ratio, SNP density were assessed to ensure G2P model exhibited superior performance in terms of prediction precision (up to 0.76 ± 0.003) and computing efficiency (within 2 h). In field trials of cadmium-contaminated farmlands in Wenling and Fuyang city, Zhejiang Province, "SMART Cd Early Warning" exhibited superior capability for identification risk rice varieties, suggesting a potential of "SMART Cd Early-Warning system" in OsGCd risk assessment and early warning in the age of smart.

Transcriptomic and physio-biochemical features in rice (Oryza sativa L.) in response to mercury stress.

Mercury (Hg) is a toxic and nonessential element for organisms, and its contamination in the environment is a global concern. Previous research has shown that Hg stress may cause severe damage to rice roots; however, the transcriptomic changes in roots and physio-biochemical responses in leaves to different levels of Hg stress are not fully understood. In the present study, rice seedlings were exposed to 20, 80, and 160 µM HgCl2 for three days in hydroponic experiments. The results showed that the majority of Hg was accumulated in rice roots after Hg exposure, and the 80- and 160-µM Hg stresses significantly increased the root-to-shoot translocation factors relative to 20-µM Hg stress, resulting in elevated Hg concentrations in rice shoots. Only the 160-µM Hg stress significantly inhibited root growth compared with the control, while photosynthesis capacity in leaves was significantly reduced under Hg stress. RNA transcriptome sequencing analyses of the roots showed that common responsive differentially expressed genes were strongly associated with glutathione metabolism, amino acid biosynthesis, and secondary metabolite metabolism, which may play significant roles in Hg accumulation by rice plants. Nine crucial genes identified by protein-protein interaction network analysis may be used as candidate target genes for further investigation of the detoxification mechanism, encoding proteins involved in jasmonic acid synthesis, sugar metabolism, allene oxide synthase, glutathione peroxidase, dismutase, and catalase. Furthermore, physio-biochemical analyses of the leaves indicated that higher production of reactive oxygen species was induced by Hg stress, while glutathione and antioxidant enzymes may play crucial roles in Hg detoxification. Our findings provide transcriptomic and physio-biochemical features of rice roots and shoots, which advance our understanding of the responsive and detoxification mechanisms in rice under different levels of Hg stress.

The systematic exploration of cadmium-accumulation characteristics of maize kernel in acidic soil with different pollution levels in China.

Cadmium is a toxic element with a half-life of more than a few decades that can be absorbed by crops and threaten human health. The problem of food security caused by cadmium through soil-crop systems has received great attention in China. Maize is a staple food widely cultivated throughout the world. However, the lack of systematic study makes it difficult to draw an accurate conclusion on its exact characteristics of cadmium accumulation and the corresponding health risk assessment. The availability of cadmium increased with the decrease of soil pH in acidic soil, enhancing the uptake of cadmium by crops and thus posing a major threat to food safety. In this study, the performance of kernel cadmium accumulation in abundant maize inbred and important hybrid lines were analyzed on acidic fields with different pollution levels in China. It was found that the kernel cadmium concentration both in inbred and hybrid lines showed left skewed distribution and concentrated significantly in a low interval under different soil cadmium gradients with good correlation. The classification of cadmium risk level in maize germplasm and cultivars and the analysis of soil cadmium threshold for maize safe planting can provide references to utilize the crop more feasibly and effectively. Maize may be an important staple crop to reduce human exposure to cadmium in agricultural soil.

Author Correction: Variation of a major facilitator superfamily gene contributes to differential cadmium accumulation between rice subspecies.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Variation of a major facilitator superfamily gene contributes to differential cadmium accumulation between rice subspecies.

Cadmium (Cd) accumulation in rice grain poses a serious threat to human health. While several transport systems have been reported, the complicity of rice Cd transport and accumulation indicates the necessity of identifying additional genes, especially those that are responsible for Cd accumulation divergence between indica and japonica rice subspecies. Here, we show that a gene, OsCd1, belonging to the major facilitator superfamily is involved in root Cd uptake and contributes to grain accumulation in rice. Natural variation in OsCd1 with a missense mutation Val449Asp is responsible for the divergence of rice grain Cd accumulation between indica and japonica. Near-isogenic line tests confirm that the indica variety carrying the japonica allele OsCd1V449 can reduce the grain Cd accumulation. Thus, the japonica allele OsCd1V449 may be useful for reducing grain Cd accumulation of indica rice cultivars through breeding.

Blocking FSH inhibits hepatic cholesterol biosynthesis and reduces serum cholesterol.

Menopause is associated with dyslipidemia and an increased risk of cardio-cerebrovascular disease. The classic view assumes that the underlying mechanism of dyslipidemia is attributed to an insufficiency of estrogen. In addition to a decrease in estrogen, circulating follicle-stimulating hormone (FSH) levels become elevated at menopause. In this study, we find that blocking FSH reduces serum cholesterol via inhibiting hepatic cholesterol biosynthesis. First, epidemiological results show that the serum FSH levels are positively correlated with the serum total cholesterol levels, even after adjustment by considering the effects of serum estrogen. In addition, the prevalence of hypercholesterolemia is significantly higher in peri-menopausal women than that in pre-menopausal women. Furthermore, we generated a mouse model of FSH elevation by intraperitoneally injecting exogenous FSH into ovariectomized (OVX) mice, in which a normal level of estrogen (E2) was maintained by exogenous supplementation. Consistently, the results indicate that FSH, independent of estrogen, increases the serum cholesterol level in this mouse model. Moreover, blocking FSH signaling by anti-FSHß antibody or ablating the FSH receptor (FSHR) gene could effectively prevent hypercholesterolemia induced by FSH injection or high-cholesterol diet feeding. Mechanistically, FSH, via binding to hepatic FSHRs, activates the Gi2α/ß-arrestin-2/Akt pathway and subsequently inhibits the binding of FoxO1 with the SREBP-2 promoter, thus preventing FoxO1 from repressing SREBP-2 gene transcription. This effect, in turn, results in the upregulation of SREBP-2, which drives HMGCR nascent transcription and de novo cholesterol biosynthesis, leading to the increase of cholesterol accumulation. This study uncovers that blocking FSH signaling might be a new strategy for treating hypercholesterolemia during menopause, particularly for women in peri-menopause characterized by FSH elevation only.

Assessment of heavy metals pollution of soybean grains in North Anhui of China.

Heavy metals may cause deleterious effects on human health through consumption of contaminated food crops. To assess the safety of soybean consumption, concentrations of heavy metals (Cu, Zn, Cr, Ni, Cd, As, Pb and Hg) in soybean grains sampled from the farmland in North Anhui (suitable for high-protein soybeans planting) were analyzed. The results showed that the concentrations of Ni, Cr, Cu and Pb in soybean gains exceeded the Chinese safety limits, with over-standard rate of 92.59%, 74.07%, 37.04% and 9.88% respectively. Spatial distribution of soybean pollution analysis showed that soybeans were severe polluted by Ni and concentrated in the west of North Anhui. SR-µXRF elemental maps of soybean gains indicated Cu, Cr, Ni, Pb and Hg specifically enriched at the embryo. In relation to health risks, there were no obvious non-carcinogenic risk and carcinogenic risk (CR) through ingesting soybeans from North Anhui. But it can induce a threat to people's health if the consumption of soybean exceeds the routine dose.

FKBP51 promotes migration and invasion of papillary thyroid carcinoma through NF-κB-dependent epithelial-to-mesenchymal transition.

FK506-binding protein 51 (FKBP51) is a member of the immunophilin family, with relevant roles in multiple signaling pathways, tumorigenesis and chemoresistance. However, the function of FKBP51 in papillary thyroid carcinoma (PTC) remains largely unknown. In the present study, increased FKBP51 expression was detected in PTC tissues as compared with adjacent normal tissues, and the expression level was associated with clinical tumor, node and metastasis stage. Using FKBP51-overexpressing K1 cells and FKBP51-knockdown TPC-1 cells, both human PTC cell lines, it was identified that FKBP51 promoted the migration and invasion of PTC, without affecting cell proliferation. Further investigation revealed that FKBP51 activated the NF-κB pathway and epithelial-to-mesenchymal transition (EMT) genes, and EMT was suppressed when NF-κB was inhibited. It was also assessed whether FKBP51 promoted the formation of cytoskeleton to promote migration and invasion of PTC using a tubulin tracker; however, no evidence of such an effect was observed. These results suggested that FKBP51 promotes migration and invasion through NF-κB-dependent EMT.

Epitope mapping and identification of amino acids critical for mouse IgG-binding to linear epitopes on Gly m Bd 28K.

Gly m Bd 28K is one of the major allergens in soybeans, but there is limited information on its IgG-binding epitopes. Thirty-four overlapping peptides that covered the entire sequence of Gly m Bd 28K were synthesized, and 3 monoclonal antibodies against Gly m Bd 28K were utilized to identify the IgG-binding regions of Gly m Bd 28K. Three dominant peptides corresponding to (28)GDKKSPKSLFLMSNS(42)(G28-S42), (56)LKSHGGRIFYRHMHI(70)(L56-I70), and (154)ETFQSFYIGGGANSH(168)(E154-H168) were recognized. L56-I70 is the most important epitope, and a competitive ELISA indicated that it could inhibit the binding of monoclonal antibody to Gly m Bd 28K protein. Alanine scanning of L56-I70 documented that F64, Y65, and R66 were the critical amino acids of this epitope. Two bioinformatics tools, ABCpred and BepiPred, were used to predict the epitopes of Gly m Bd 28K, and the predictions were compared with the epitopes that we had located by monoclonal antibodies.

An aquaporin PvTIP4;1 from Pteris vittata may mediate arsenite uptake.

The fern Pteris vittata is an arsenic hyperaccumulator. The genes involved in arsenite (As(III)) transport are not yet clear. Here, we describe the isolation and characterization of a new P. vittata aquaporin gene, PvTIP4;1, which may mediate As(III) uptake. PvTIP4;1 was identified from yeast functional complement cDNA library of P. vittata. Arsenic toxicity and accumulating activities of PvTIP4;1 were analyzed in Saccharomyces cerevisiae and Arabidopsis. Subcellular localization of PvTIP4;1-GFP fusion protein in P. vittata protoplast and callus was conducted. The tissue expression of PvTIP4;1 was investigated by quantitative real-time PCR. Site-directed mutagenesis of the PvTIP4;1 aromatic/arginine (Ar/R) domain was studied. Heterologous expression in yeast demonstrates that PvTIP4;1 was able to facilitate As(III) diffusion. Transgenic Arabidopsis showed that PvTIP4;1 increases arsenic accumulation and induces arsenic sensitivity. Images and FM4-64 staining suggest that PvTIP4;1 localizes to the plasma membrane in P. vittata cells. A tissue location study shows that PvTIP4;1 transcripts are mainly expressed in roots. Site-directed mutation in yeast further proved that the cysteine at the LE1 position of PvTIP4;1 Ar/R domain is a functional site. PvTIP4;1 is a new represented tonoplast intrinsic protein (TIP) aquaporin from P. vittata and the function and location results imply that PvTIP4;1 may be involved in As(III) uptake.