The complete chloroplast genome of Illicium simonsii Maxim. (Illiciaceae), a species with important medicinal properties.

Illicium simonsii Maxim (1888) is a medicinal species of the genus Illicium in the Illiciaceae family. It is commonly used to cure gastro-frigid vomiting, cystic hernia, gas pains in the chest, and scabies as folk medicine. To utilize its resources efficiently, the complete chloroplast genome of I. simonsii was sequenced, assembled, and annotated by using high-throughput sequencing data. The complete chloroplast genome was 143,038 bp in length, with a large single-copy region (LSC) of 101,094 bp, a short single-copy region (SSC) of 20,070 bp, and a pair of inverted repeats (IRs) of 21,874 bp. A total of 113 genes were annotated, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. The phylogenetic tree exhibited that I. simonsii and Illicium burmanicum form a sister group, and were nested in the monophyletic clade of the Illicium genus.

Ling-Gui-Qi-Hua formula alleviates left ventricular myocardial fibrosis in rats with heart failure with preserved ejection fraction by blocking the transforming growth factor-ß1 /Smads signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ling-Qui-Qi-Hua (LGQH) decoction, composed of Poria cocos (Schw.) Wolf, Cinnamomum cassia (L.) J. Presl, Paeonia veitchii Lynch, and Atractylodes macrocephala Koidz., is a compound formula derived from Ling-Gui-Zhu-Gan decoction recorded in the Treatise on Febrile and Miscellaneous. It has shown cardioprotective effects on patients or rats with heart failure with preserved ejection fraction (HFpEF). Nevertheless, the active ingredients of LGQH and its anti-fibrotic mechanism remain unknown. AIM OF THE STUDY: To determine the active ingredients in LGQH decoction and verify that LGQH decoction may inhibit left ventricular (LV) myocardial fibrosis in HFpEF rats by blocking the transforming growth factor-ß1 (TGF-ß1)/Smads signaling pathway from the perspective of animal experiments. MATERIALS AND METHODS: First, liquid chromatography-mass spectrometry (LC-MS) technology was used to identify active components in the LGQH decoction. Secondly, a rat model of the metabolic syndrome-associated HFpEF phenotype was established and subsequently received LGQH intervention. The mRNA and protein expression of targets in the TGF-ß1/Smads pathway were detected by quantitative real-time polymerase chain reaction and western blot analysis. Finally, molecular docking was conducted to examine the interactions between the active ingredients in the LGQH decoction and key proteins of the TGF-ß1/Smads pathways. RESULTS: According to LC-MS analysis, the LGQH decoction contained 13 active ingredients. In animal experiments, LGQH attenuated LV hypertrophy, enlargement, and diastolic function in HEpEF rats. Mechanically, LGQH not only down-regulated TGF-ß1, Smad2, Smad3, Smad4, α-SMA, Coll I, and Coll III mRNA expressions and TGF-ß1, Smad2, Smad3, P-Smad2/Smad3, Smad4, α-SMA, and Coll I protein expressions, but also up-regulated Smad7 mRNA and protein expressions, which ultimately led to myocardial fibrosis. Furthermore, molecular docking confirmed that 13 active ingredients in the LGQH decoction have excellent binding activities to the critical targets of the TGF-ß1/Smads pathway. CONCLUSION: LGQH is a modified herbal formulation with multiple active ingredients. It might alleviate LV remodeling and diastolic dysfunction and inhibit LV myocardial fibrosis by blocking TGF-ß1/Smads pathways in HFpEF rats.

Effects and mechanism of Compound Qidan Formula on rats with HFpEF induced by hypertension and diabetes mellitus based on Ang â ¡/TGF-ß1/Smads signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Qidan Formula is composed of traditional Chinese herbs and has a good curative effect in the clinical application of cardiovascular diseases such as heart failure. However, its potential molecular mechanisms of action remain highly unknown. AIM OF THE STUDY: To observe the effect of Compound Qidan Formula on cardiac function in rats with HFpEF induced by hypertension and diabetes mellitus, and to explore its mechanism from Ang Ⅱ/TGF-ß1/Smads signaling pathway. MATERIALS AND METHODS: A total of 50 SPF-grade spontaneously hypertensive rats (SHR) aged 14 weeks, fed with a high-fat and high-sucrose diet for 16 weeks, and after 2 weeks of a high-fat and high-sucrose diet, 1% streptozotocin (25 mg/kg body weight)was injected intraperitoneally to establish a rat model of HFpEF induced by hypertension and diabetes mellitus. After 8 weeks of intragastric administration, the changes in cardiac morphology and function were evaluated by echocardiography after anesthesia; the heart tissue was taken and embedded in paraffin for Masson staining, and the pathomorphological changes of left atrial tissue were observed under the optical microscope; the mRNA transcription levels of Ang Ⅱ, AT1R, TGF-ß1, Smad2, Smad3, MMP-9 and TIMP-1in left atrial tissue of rats were detected by RT-PCR; and the protein expressions were detected by Western blot. RESULTS: Compared with the SHR-DM group, the QD-Low and QD-High groups significantly decreased the left atrial (LA) anteroposterior diameter and interventricular septal thickness (IVST) and improved the peak velocity of mitral valve blood flow in early diastolic period (E), maximum mitral valve blood flow in systolic period (A), mitral ring myocardial movement velocity in early diastolic period (e') and E/e' ratio; the QD-High group significantly improved the E/A ratio, left atrial ejection fraction (LAEF) and left ventricular ejection fraction(LVEF). Masson staining showed that compared with the WKY group, the SHR-DM group had obvious myocardial histomorphological lesions. Compared with the SHR-DM group, the Compound Qidan Formula groups significantly improved cardiomyocyte hypertrophy and disordered arrangement and inhibited myocardial fibrosis; the mRNA expression levels of Ang Ⅱ, AT1R, TGF-ß1, Smad2, Smad3, and MMP-9 in myocardial tissue of Compound Qidan Formula groups were significantly decreased, and the mRNA expression level of TIMP-1 was significantly increased. The protein expression levels of Ang Ⅱ, TGF-ß1, P-Smad2/3, and MMP-9 were significantly decreased. CONCLUSION: Compound Qidan Formula, composed of traditional Chinese herbs, can significantly improve cardiac function, improve atrial and ventricular remodeling, and prevent myocardial fibrosis and hypertrophy in rats with HFpEF induced by hypertension and diabetes mellitus. The mechanism may be related to regulating the Ang Ⅱ/TGF-ß1/Smad2/3 signaling pathway.

Linggui Qihua Decoction Inhibits Atrial Fibrosis by Regulating TGF-ß1/Smad2/3 Signal Pathway.

Myocardial fibrosis is a critical factor in the development of heart failure with preserved ejection fraction (HFpEF). Linggui Qihua decoction (LGQHD) is an experienced formula, which has been proven to be effective on HFpEF in clinical and in experiments. Objective. This study aimed to observe the effect of LGQHD on HFpEF and its underlying mechanism. Methods. Spontaneously hypertensive rats (SHR) were induced with high-glucose and high-fat to establish HFpEF models and were treated with LGQHD for 8 weeks. The heart structure was detected by echocardiography, and the histopathological changes of the myocardium were observed by hematoxylin-eosin (HE) and Masson staining. Reverse transcription PCR (RT-PCR) and western blot were used to detect mRNA and protein expression of the target gene in rat myocardium. Results. In this study, LGQHD improved cardiac morphology and atrial fibrosis in HfpEF rats, decreased tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expression, up-regulated matrix metalloproteinase-9 (MMP-9) mRNA expression, and inhibited the expression of angiotensin II (Ang II), angiotensin II type 1 receptor (AT1), transforming growth factor ß1 (TGF-ß1), Smad2/3 mRNA, and protein in myocardial tissue of HFpEF rats. Conclusion. LGQHD can suppress atrial fibrosis in HFpEF by modulating the TGF-ß1/Smad2/3 pathway.

Calcium and magnesium in China's public drinking water and their daily estimated average requirements.

Calcium (Ca) and magnesium (Mg) in drinking water and the relevant health effects have been ignored for too long. This study aims to reveal the concentrations, spatial distributions, origins and contributions to the daily estimated average requirements of Ca and Mg in public drinking water. Using hydrochemical data of collected samples of public drinking water in 314 cities across China, the contributions of Ca and Mg intakes from public drinking water to their daily estimated average requirements (EARs) were assessed. And the significance of Ca/Mg ratio and total hardness (TH) was evaluated as well. The Ca and Mg concentrations of the samples were in the range of 2.5-155.1 mg/L and 0.2-81.9 mg/L, with an average of 40.4 mg/L and 12.4 mg/L, respectively. There exist obvious differences in Ca and Mg concentrations in different regions, under the impact of climate conditions and water-rock interactions. The intake of Ca via the consumption of public drinking water for adults may be twice as much as that for other age groups. In cities with high Ca levels in public drinking water, the Ca contributions to EAR could reach up to 51.59% for adults. By contrast, Mg in drinking water is an important and even the main pathway to ingest Mg for infants and children. Therefore, public drinking water is critical for Ca and Mg intake among urban residents of China. Besides, attention should be paid to the health effects of high Ca/Mg ratio and low TH in public drinking water, especially in southern China. This research is the first systematic and comprehensive national scale study of Ca and Mg in public drinking water and can provide an important reference to improve healthy public drinking water standards around the world.

Chemical Structures and Antioxidant Activities of Polysaccharides from Carthamus tinctorius L.

Two polysaccharides from Carthamus tinctorius L. (CTLP-1 and CTLP-2) were purified, and their structures were analyzed by physical and chemical testing. CTLP-1 had a mass of 5900 Da that was composed of arabinose, glucose, and galactose with a mass molar ratio of 6.7:4.2:1. The backbone of CTLP-1 was →1)-α-GalAp-(1→4)-α-Arap-(1→2)-α-Glup-(4→. CTLP-2 had a mass of 8200 Da that was composed of arabinose, glucose, and galactose with a mass molar ratio of 16.76:4.28:1. The backbone of CTLP-2 was →1)-α-Galp-(2,6 →1)-α-Arap-(4,6 →1)-α-Glup-(3→. Both of them exhibited a high reducing power, hydroxyl radical scavenging activity, DPPH radical scavenging activity and ABTS radical scavenging activity, moderate Fe2+ chelating activity and superoxide anion scavenging activity, implying that they might be potential antioxidants.

Trace elements in public drinking water in Chinese cities: Insights from their health risks and mineral nutrition assessments.

The trace elements in the public drinking water have a duality: on the one hand, trace elements play an important role in maintaining human metabolism; on the other hand, high trace elements levels lead to significant health risks. To determine the impacts of trace elements in the public drinking water on physical health in China, water samples were collected from 314 Chinese cities to analyze the concentrations and spatial distributions of trace elements on a national scale. On this basis, the non-carcinogenic health risk assessments and the nutrient-based scores of trace elements (NSTEs) were applied to evaluate the public drinking water quality in terms of safety and nutrition. Most of the water samples were weakly alkaline: pH values fell in the range of 6.62-8.54, with a mean of 7.80. The results indicated that Sr and F- had the highest concentrations in public drinking water, with averages of 0.3604 mg/L and 0.2351 mg/L, respectively. Moreover, hazard index (HI) values in different regions followed the order: northwest China (NWC) > northern China (NC) > Qinghai-Tibetan Plateau (QT) > southern China (SC). The percentages of water samples with HI > 1 in SC, NC, NWC, and QT were 5.49%, 16.82%, 25.81%, and 16.67%, respectively, indicating that the public drinking water in some cities had significant non-carcinogenic health risks. In addition, the intakes of Mn, Fe, Cu, and Rb through public drinking water made negligible contributions to their recommended nutrient intakes. In contrast, trace elements like Sr, F, B, Li, Mo, etc., contributed a lot. The NSTEs in NWC and most parts of NC were relatively high with averages of 8.0300 and 11.2082, respectively; however, the NSTEs in SC and the northeast part of NC were low with averages of 3.3284 and 5.2106, respectively. The results from this study provide a reference for establishing the public drinking water standards and improving drinking water quality.

Analgesic Effects of Repetitive Transcranial Magnetic Stimulation in Patients With Advanced Non-Small-Cell Lung Cancer: A Randomized, Sham-Controlled, Pilot Study.

Objective: Current pharmacological intervention for the cancer-related pain is still limited. The aim of this study was to explore whether repetitive transcranial magnetic stimulation (rTMS) could be an effective adjuvant therapy to reduce pain in patients with advanced non-small cell lung cancer (NSCLC). Methods: This was a randomized, sham-controlled study. A total of 41 advanced NSCLC patients with uncontrolled pain (score≥4 on pain intensity assessed with an 11-point numeric rating scale) were randomized to receive active (10 Hz, 2000 stimuli) (n = 20) or sham rTMS (n = 20) for 3 weeks. Pain was the primary outcome and was assessed with the Numeric Rating Scale (NRS). Secondary outcomes were oral morphine equivalent (OME) daily dose, quality of life (WHO Quality of Life-BREF), and psychological distress (the Hospital Depression and Anxiety Scale). All outcomes were measured at baseline, 3 days, 1 week, 2 weeks, and 3 weeks. Results: The pain intensity in both groups decreased gradually from day 3 and decreased to the lowest at the week 3, with a decrease rate of 41.09% in the rTMS group and 23.23% in the sham group. The NRS score of the rTMS group was significantly lower than that of the sham group on the week 2 (p < 0.001, Cohen's d =1.135) and week 3 (p=0.017, Cohen's d = -0.822). The OME daily dose, physiology and psychology domains of WHOQOL-BREF scores, as well as the HAM-A and HAM-D scores all were significantly improved at week 3 in rTMS group. Conclusion: Advanced NSCL patients with cancer pain treated with rTMS showed better greater pain relief, lower dosage of opioid, and better mood states and quality of life. rTMS is expected to be a new effective adjuvant therapy for cancer pain in advanced NSCLC patients.

Hydrochemical characteristics and quality assessment of shallow groundwater in Yangtze River Delta of eastern China.

Water resource is in high demand within the Yangtze River Delta, given its developed economy. Long-term exploitation of this resource has posed risks of artificial pollution and seawater intrusion to the shallow groundwater. This study aims to reveal the hydrochemical characteristics and health risks of shallow groundwater in the coastal plain of the Yangtze River Delta, as well as to discuss the possible factors affecting groundwater quality. Standard methods for hydrochemical parameter measurements, water quality assessment, and health risk models were applied to fulfill the objectives of the study. The results showed that the shallow groundwater was slightly alkaline, and the average values of total dissolved solids (TDS) and total hardness (TH) were 930.74 mg/L and 436.20 mg/L, respectively. The main hydrochemical types of groundwater were HCO3-Ca·Mg and HCO3-Ca·Na, accounting for 44.3% and 47.5%, respectively. In addition, As concentration was generally high, with a mean value of 0.0115 mg/L. The principal factors affecting the groundwater components include water-rock interactions (especially silicate), cation exchange, seawater intrusion, and human activities. The data also showed that As is strongly influenced by the redox of Fe, Mn, and NO3-. The results of the groundwater quality evaluation indicated that the shallow groundwater in some regions was unsuitable for drinking and agricultural irrigation. Health risk assessment showed that 44.3% of the water samples had significant health risks, which was attributed to the high As concentration. Therefore, it is urgent to establish long-term As monitoring to maintain sustainable groundwater management and drinking water safety. The results of this study provide essential data for water resource management and human health security in the Yangtze River Delta.

Identification of Novel Key Genes and Pathways in Multiple Sclerosis Based on Weighted Gene Coexpression Network Analysis and Long Noncoding RNA-Associated Competing Endogenous RNA Network.

Objective: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by chronic inflammation and demyelination. This study is aimed at identifying crucial genes and molecular pathways involved in MS pathogenesis. Methods: Raw data in GSE52139 were collected from the Gene Expression Omnibus. The top 50% expression variants were subjected to weighted gene coexpression network analysis (WGCNA), and the key module associated with MS occurrence was identified. A long noncoding RNA- (lncRNA-) associated competing endogenous RNA (ceRNA) network was constructed in the key module. The hub gene candidates were subsequently verified in an individual database. Results: Of the 18 modules obtained, the cyan module was designated as the key module. The established ceRNA network was composed of seven lncRNAs, 45 mRNAs, and 21 microRNAs (miRNAs), and the FAM13A-AS1 was the lncRNA with the highest centrality. Functional assessments indicated that the genes in the cyan module primarily gathered in ribosome-related functional terms. Interestingly, the targeted mRNAs of the ceRNA network enriched in diverse categories. Moreover, highly expressed CYBRD1, GNG12, and SMAD1, which were identified as hub genes, may be associated with "valine leucine and isoleucine degradation," "base excision repair," and "fatty acid metabolism," respectively, according to the results of single gene-based genomes and gene set enrichment analysis (GSEA). Conclusions: Combined with the WGCNA and ceRNA network, our findings provide novel insights into the pathogenesis of MS. The hub genes discovered herein might also serve as novel biomarkers that correlate with the development and management of MS.

Identification of novel biomarkers for intracerebral hemorrhage via long noncoding RNA-associated competing endogenous RNA network.

Intracerebral hemorrhage (ICH) is a leading cause of death and disability worldwide. This study aimed to examine the involvement of long non-coding RNAs (lncRNAs), a group of non-coding transcripts, in ICH as potential biomarkers. An expression profile of patients with ICH using four contralateral grey matter controls (GM) and four contralateral white matter controls (WM) was downloaded from the Gene Expression Omnibus (GEO) database. Co-expressed lncRNAs and mRNAs were selected to create competing endogenous RNA (ceRNA) networks. Key lncRNAs were identified in ceRNA networks, which were validated through Real-time qPCR (RT-qPCR) with peripheral blood samples from patients with ICH. A total of 49 differentially expressed lncRNAs were discovered in different brain regions. The ceRNA network in GM included 9 lncRNAs, 40 mRNAs, and 20 microRNAs (miRNAs), while the one in WM covered 6 lncRNAs, 25 mRNAs, and 14 miRNAs. Six hub lncRNAs were observed and RT-qPCR results showed that LY86-AS1, DLX6-AS1, RRN3P2, and CRNDE were down-regulated, while HCP5 and MIAT were up-regulated in patients with ICH. Receiver Operating Characteristic (ROC) assessments demonstrated the diagnostic value of these lncRNAs. Our findings highlight the potential roles of lncRNA in ICH pathogenesis. Moreover, the hub lncRNAs discovered here might become novel biomarkers and promising targets for ICH drug development.

A cellular mechanism underlying the restoration of thermo/photoperiod-sensitive genic male sterility.

During anther development, the transformation of the microspore into mature pollen occurs under the protection of first the tetrad wall and later the pollen wall. Mutations in genes involved in this wall transition often lead to microspore rupture and male sterility; some such mutants, such as the reversible male sterile (rvms) mutant, are thermo/photoperiod-sensitive genic male sterile (P/TGMS) lines. Previous studies have shown that slow development is a general mechanism of P/TGMS fertility restoration. In this study, we identified restorer of rvms-2 (res2), which is an allele of QUARTET 3 (QRT3) encoding a polygalacturonase that shows delayed degradation of the tetrad pectin wall. We found that MS188, a tapetum-specific transcription factor essential for pollen wall formation, can activate QRT3 expression for pectin wall degradation, indicating a non-cell-autonomous pathway involved in the regulation of the cell wall transition. Further assays showed that a delay in degradation of the tetrad pectin wall is responsible for the fertility restoration of rvms and other P/TGMS lines, whereas early expression of QRT3 eliminates low temperature restoration of rvms-2 fertility. Taken together, these results suggest a likely cellular mechanism of fertility restoration in P/TGMS lines, that is, slow development during the cell wall transition of P/TGMS microspores may reduce the requirement for their wall protection and thus support their development into functional pollens, leading to restored fertility.

[Screening of Amendments for Simultaneous Cd and As Immobilization in Soil].

Simultaneously reducing the availability of Cd and As is difficult owing to converse chemical behaviors of Cd and As in soil. In this study, amendments that can simultaneously immobilize Cd and As in soil were determined by an pure soil culture experiment in which flooding and wetting were performed for 30 d each. The effects of sepiolite (Sep), modified sepiolite (IMS and Sep-FM), steel slag (SS), and iron modified biochar (Fe-Bio) on soil pH, Eh, Cd, and As concentrations in pore water, and Cd and As fractions in soil were investigated. It showed that Sep (1%, 2.5%), IMS (1%, 2.5%), Sep-FM (1%, 2.5%), and SS (1%, 5%) treatments increased soil pH value and decreased Eh value and Cd concentrations in soil solution. In addition, As concentrations in soil solution treated with high doses of IMS (2.5%) and SS (5%) were lower than that of CK treatment during the whole incubation period. However, Fe-bio treatment decreased soil pH and increased Eh value and only decreased Cd and As concentrations in soil solution under wet conditions. Compared with the control, the application of the above amendments promoted the transformation of Cd fraction from exchangeable to reducible, oxidizable, and residual. High application rates of IMS (2.5%), Sep-FM (2.5%), and SS (5%) also reduced available As fraction (non-specifically sorbed and specifically-sorbed As fraction), and increased amorphous and poorly-crystalline hydrated Fe and Al oxide-bound As. On the contrary, Fe-bio treatment increased the fractions of non-specifically sorbed, specifically sorbed and residual As in soil. In short, IMS, Sep-FM, and SS are potential materials for remediation of Cd and As contaminated soil. They can effectively immobilize soil Cd and As and promote their transformation to the fractions that plants are difficult to uptake.

Elements in potable groundwater in Rugao longevity area, China: Hydrogeochemical characteristics, enrichment patterns and health assessments.

Rugao city is a typical longevity area taking shallow groundwater as the primary drinking water source. To determine the relationship between longevity and groundwater conditions, the hydrogeochemical characteristics and related causes of potable groundwater were investigated. On this basis, the water quality index (WQI) and hazard index (HI) of groundwater were evaluated. Meanwhile, the nutrient indicators beneficial to human health, like Ca and Mg concentrations, were also considered to explore the relationship. The results were as following: (1) 91.3% of water samples fell under the Ca/Mg-HCO3 water type, which resulted from the dissolution of silicate rock. Na, Cl-, Br, B in groundwater emanated from seawater intrusion. The abnormal concentrations of NO3- and As also indicated that anthropogenic activities had exerted significant influences on groundwater quality. (2) The average WQI value was 30.19, which meant that the overall groundwater quality in Rugao city was pretty good. However, 8 water samples were found to have HI values above 1, which might be attributed to the high concentration of As (maximum value 0.0407 mg/L; mean value 0.0076 mg/L). In general, low WQI and HI values corresponded to towns with a high longevity population; what's more, WQI and HI values of Rugao city were lower than those of non-longevity areas. (3) Comparing with adjacent non-longevity areas, the potable groundwater in Rugao city had the characteristics of high Ca (mean value 123.57 mg/L), high Mg (mean value 50.33 mg/L) and high SO42- (mean value 525.19 mg/L). The daily intake of Ca and Mg from drinking water could meet 12.4% and 22.4% of daily Ca and Mg requirements, respectively. Also, the areas where the Sr and B concentrations were higher usually had higher life expectancy. The high concentrations of Ca, Mg, SO42-, Sr and B in drinking water, as well as low WQI and HI values, probably contribute to physical health and longevity. This research helps provide an insight into the relationship between groundwater quality and health and can serve as a reference for drinking water quality management.

PANX2 and brain lower grade glioma genesis: A bioinformatic analysis.

PANX2 forms large-pore channels mediating ATP release in response to physiological and pathological stimuli. Although PANX2 shows involvements in glioma genesis, the underlying mechanism remains unclear. PANX2 mRNA expression was analyzed via Oncomine and was confirmed via Gene Expression Profiling Interactive Analysis (GEPIA). The influence of PANX2 on overall survival (OS) of glioma was evaluated using LinkedOmics and further assessed through Cox regression analysis. The correlated genes with PANX2 acquired from LinkedOmics were validated through GEPIA and cBioPortal. Protein-protein interaction (PPI) of these genes was then obtained using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape with MCODE plug-in. All the PANX2-related genes underwent Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The correlation between PANX2 and cancer immune infiltrates was evaluated via Tumor Immune Estimation Resource (TIMER). A higher expression of PANX2 only revealed a better OS in brain low grade glioma (LGG). PANX2-related genes in LGG functionally enriched in neuroactive ligand-receptor interaction, synaptic vesicle cycle, and calcium signaling. The hub genes from highest module of PPI were mainly linked to chemical synaptic transmission, plasma membrane, neuropeptide, and the pathway of neuroactive ligand-receptor interaction. Besides, PANX2 expression was negatively associated with infiltrating levels of macrophage, dendritic cells, and CD4+ T cells. This study demonstrated that PANX2 likely participated in LGG pathogenesis by affecting multiple molecular pathways and immune-related processes. PANX2 was associated with LGG prognosis and might become a promising therapeutic target of LGG.

Assessment of Weighted Gene Co-Expression Network Analysis to Explore Key Pathways and Novel Biomarkers in Muscular Dystrophy.

PURPOSE: This study aimed to explore the key molecular pathways involved in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) and thereby identify hub genes to be potentially used as novel biomarkers using a bioinformatics approach. METHODS: Raw GSE109178 data were collected from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was conducted on the top 50% of altered genes. The key modules associated with the clinical features of DMD and BMD were identified. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the DAVID website. A protein-protein interaction (PPI) network was constructed using the STRING website. MCODE, together with the Cytohubba plug-ins of Cytoscape, screened out the potential hub genes, which were subsequently verified via receiver operating characteristic (ROC) curves in other datasets. RESULTS: Among the 11 modules obtained, the black module was predominantly associated with pathology and DMD, whereas the light-green module was primarily related to age and BMD. Functional enrichment assessments indicated that the genes in the black module were primarily clustered in "immune response" and "phagosome," whereas the ones in the light-green module were chiefly enriched in "protein polyubiquitination". Eleven essential genes were eventually identified, including VCAM1, TYROBP, CD44, ITGB2, CSF1R, LCP2, C3AR1, CCL2, and ITGAM for DMD, along with UBA5 and UBR2 for BMD. CONCLUSION: Overall, our findings may be useful for investigating the mechanisms underlying DMD and BMD. In addition, the hub genes discovered might serve as novel molecular markers correlated with dystrophinopathies.

Strontium in public drinking water and associated public health risks in Chinese cities.

Due to the fact that strontium (Sr) is not involved in the scope of supervision of drinking water in China, the Sr concentration in public drinking water and its related health risks have been neglected for a long time. In this research, public drinking water samples were collected from 314 cities across the country to reveal the concentration and spatial distribution of Sr in public drinking water. In addition, the Monte Carlo method (a statistical simulation method) was applied to evaluate the Sr intake from drinking water and human health risks among different age groups and different regions. As shown in the results, the Sr was in the concentration range of 0.005-3.11 mg/L with a mean value of 0.360 mg/L. There were significant differences in the Sr concentration in different regions; in general, it was high in the north and low in the south. The Sr intakes of infants, children, teens, and adults from drinking water were 0.273, 0.503, 0.633, and 0.784 mg/day, respectively. There was a significant positive correlation between Sr concentration in drinking water and bone mineral density (BMD) in the elderly. Especially, the correlation coefficients (r) between Sr concentration and the BMD of the elderly whose age fell in the range of 60-70 years were 0.692 (male) and 0.483 (female). In addition, the Sr concentration in drinking water was positively correlated with the incidence of children's rickets (r = 0.411), while the Ca/Br ratio was negatively correlated with the incidence of children's rickets (r = - 0.410). According to the health risk assessment, among people of different ages, infants' hazard index (HI) value was the highest. The mean value and 95th percentile value were 0.066 and 0.247. Non-carcinogenic risk of Sr through drinking water among different people in different regions was less than 1, which meant no significant damage to human health. This study is the first time to systematically investigate Sr in public drinking water across the whole country. More importantly, the conclusions can be applied to risk control and management of public drinking water.

Comprehensive Analysis of Long Non-coding RNA-Associated Competing Endogenous RNA Network in Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is one of the most severe neuromuscular disorders. Long non-coding RNAs (lncRNAs) are a group of non-coding transcripts, which could regulate messenger RNA (mRNA) by binding the mutual miRNAs, thus acting as competing endogenous RNAs (ceRNAs). So far, the role of lncRNA in DMD pathogenesis remains unclear. In the current study, expression profile from a total of 33 DMD patients and 12 healthy people were downloaded from Gene Expression Omnibus (GEO) database (GSE38417 and GSE109178). Differentially expressed (DE) lncRNAs were discovered and targeted mRNAs were predicted. The ceRNA network of lncRNAs-miRNAs-mRNAs was then constructed. Genome Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the putative mRNAs in the ceRNA network were performed through Database for Annotation, Visualization and Integration Discovery (DAVID) website. Topological property of the network was analyzed using Cytoscape to disclose the hub lncRNAs. According to our assessments, 19 common DElncRNAs and 846 common DEmRNAs were identified in DMD compared to controls. The created ceRNA network contained 6 lncRNA nodes, 69 mRNA nodes, 27 miRNA nodes and 102 edges, while four hub lncRNAs (XIST, AL132709, LINC00310, ALDH1L1-AS2) were uncovered. In conclusion, our latest bioinformatic analysis demonstrated that lncRNA is likely involved in DMD. This work highlights the importance of lncRNA and provides new insights for exploring the molecular mechanism of DMD. The created ceRNA network contained 6 lncRNA nodes, 69 mRNA nodes, 27 miRNA nodes and 102 edges, while four hub lncRNAs (XIST, AL132709, LINC00310, ALDH1L1-AS2) were uncovered. Remarkably, KEGG analysis indicated that targeted mRNAs in the network were mainly enriched in "microRNAs in cancer" and "proteoglycans in cancer". Our study may offer novel perspectives on the pathogenesis of DMD from the point of lncRNAs. This work might be also conducive for exploring the molecular mechanism of increased incidence of tumorigenesis reported in DMD patients and experimental models.

MS1, a direct target of MS188, regulates the expression of key sporophytic pollen coat protein genes in Arabidopsis.

Sporophytic pollen coat proteins (sPCPs) derived from the anther tapetum are deposited into pollen wall cavities and function in pollen-stigma interactions, pollen hydration, and environmental protection. In Arabidopsis, 13 highly abundant proteins have been identified in pollen coat, including seven major glycine-rich proteins GRP14, 16, 17, 18, 19, 20, and GRP-oleosin; two caleosin-related family proteins (AT1G23240 and AT1G23250); three lipase proteins EXL4, EXL5 and EXL6, and ATA27/BGLU20. Here, we show that GRP14, 17, 18, 19, and EXL4 and EXL6 fused with green fluorescent protein (GFP) are translated in the tapetum and then accumulate in the anther locule following tapetum degeneration. The expression of these sPCPs is dependent on two essential tapetum transcription factors, MALE STERILE188 (MS188) and MALE STERILITY 1 (MS1). The majority of sPCP genes are up-regulated within 30 h after MS1 induction and could be restored by MS1 expression driven by the MS188 promoter in ms188, indicating that MS1 is sufficient to activate their expression; however, additional MS1 downstream factors appear to be required for high-level sPCP expression. Our ChIP, in vivo transactivation assay, and EMSA data indicate that MS188 directly activates MS1. Together, these results reveal a regulatory cascade whereby outer pollen wall formation is regulated by MS188 followed by synthesis of sPCPs controlled by MS1.

The temporal regulation of TEK contributes to pollen wall exine patterning.

Pollen wall consists of several complex layers which form elaborate species-specific patterns. In Arabidopsis, the transcription factor ABORTED MICROSPORE (AMS) is a master regulator of exine formation, and another transcription factor, TRANSPOSABLE ELEMENT SILENCING VIA AT-HOOK (TEK), specifies formation of the nexine layer. However, knowledge regarding the temporal regulatory roles of TEK in pollen wall development is limited. Here, TEK-GFP driven by the AMS promoter was prematurely expressed in the tapetal nuclei, leading to complete male sterility in the pAMS:TEK-GFP (pat) transgenic lines with the wild-type background. Cytological observations in the pat anthers showed impaired callose synthesis and aberrant exine patterning. CALLOSE SYNTHASE5 (CalS5) is required for callose synthesis, and expression of CalS5 in pat plants was significantly reduced. We demonstrated that TEK negatively regulates CalS5 expression after the tetrad stage in wild-type anthers and further discovered that premature TEK-GFP in pat directly represses CalS5 expression through histone modification. Our findings show that TEK flexibly mediates its different functions via different temporal regulation, revealing that the temporal regulation of TEK is essential for exine patterning. Moreover, the result that the repression of CalS5 by TEK after the tetrad stage coincides with the timing of callose wall dissolution suggests that tapetum utilizes temporal regulation of genes to stop callose wall synthesis, which, together with the activation of callase activity, achieves microspore release and pollen wall patterning.