Targeting RNA G-quadruplex with repurposed drugs blocks SARS-CoV-2 entry.

The rapid emergence of SARS-CoV-2 variants of concern, the complexity of infection, and the functional redundancy of host factors, underscore an urgent need for broad-spectrum antivirals against the continuous COVID-19 pandemic, with drug repurposing as a viable therapeutic strategy. Here we report the potential of RNA G-quadruplex (RG4)-targeting therapeutic strategy for SARS-CoV-2 entry. Combining bioinformatics, biochemical and biophysical approaches, we characterize the existence of RG4s in several SARS-CoV-2 host factors. In silico screening followed by experimental validation identify Topotecan (TPT) and Berbamine (BBM), two clinical approved drugs, as RG4-stabilizing agents with repurposing potential for COVID-19. Both TPT and BBM can reduce the protein level of RG4-containing host factors, including ACE2, AXL, FURIN, and TMPRSS2. Intriguingly, TPT and BBM block SARS-CoV-2 pseudovirus entry into target cells in vitro and murine tissues in vivo. These findings emphasize the significance of RG4 in SARS-CoV-2 pathogenesis and provide a potential broad-spectrum antiviral strategy for COVID-19 prevention and treatment.

Extrachromosomal circular MiR-17-92 amplicon promotes HCC.

BACKGROUND AND AIMS: Extrachromosomal circular DNAs (eccDNAs) are prevalent in cancer genomes and emerge as a class of crucial yet less characterized oncogenic drivers. However, the structure, composition, genome-wide frequency, and contribution of eccDNAs in HCC, one of the most fatal and prevalent cancers, remain unexplored. In this study, we provide a comprehensive characterization of eccDNAs in human HCC and demonstrate an oncogenic role of microRNA (miRNA)-17-92-containing eccDNAs in tumor progression. APPROACH AND RESULTS: Using the circle-sequencing method, we identify and characterize more than 230,000 eccDNAs from 4 paired samples of HCC tumor and adjacent nontumor liver tissues. EccDNAs are highly enriched in HCC tumors, preferentially originate from certain chromosomal hotspots, and are correlated with differential gene expression. Particularly, a series of eccDNAs carrying the miRNA-17-92 cluster are validated by outward PCR and Sanger sequencing. Quantitative PCR analyses reveal that miRNA-17-92-containing eccDNAs, along with the expression of their corresponding miRNAs, are elevated in HCC tumors and associated with poor outcomes and the age of HCC patients. More intriguingly, exogenous expression of artificial DNA circles harboring the miR-17-92 cluster, which is synthesized by the ligase-assisted minicircle accumulation method, can significantly accelerate HCC cell proliferation and migration. CONCLUSIONS: These findings delineate the genome-wide eccDNAs profiling of HCC and highlight the functional significance of miRNA-containing eccDNAs in tumorigenesis, providing insight into HCC pathogenesis and cancer therapy, as well as eccDNA and miRNA biology.

Effects of a special continuous quality improvement in nursing on the management of adverse care events: a retrospective study.

OBJECTIVE: To explore the application effect of the direct reporting system of adverse nursing events and special continuous nursing quality improvement measures in the management of these adverse events. METHODS: The implementation time of continuous nursing improvement based on the direct reporting system was the demarcation point. We retrospectively collected and analyzed nursing adverse event reports and hospitalization data from Xiangtan Central Hospital before implementation (2015-2018) and after implementation (2019-2022). The active reporting rate of adverse events, the composition of these events and the processing time were compared between the two groups. RESULTS: The rate of active reporting of adverse events before the implementation was lower than that after the implementation (6.7% vs. 8.1%, X2 = 25.561, P < 0.001). After the implementation of the direct reporting system for nursing events and the continuous improvement of nursing quality, the reporting proportion of first-level and second-level events decreased significantly. Moreover, the reporting proportion of third-level events increased significantly. The proportion of falls and medication errors decreased, and the proportion of unplanned extubation, infusion xerostomia and improper operation increased. The processing time of the reported nursing adverse events was significantly reduced (31.87 ± 7.83 vs. 56.87 ± 8.21, t = 18.73, P < 0.001). CONCLUSION: The direct reporting system of adverse nursing events and the continuous improvement measures for nursing quality can effectively improve the active reporting rate of adverse events, change their composition and reduce their processing time, as well as help create a safe psychological environment for both patients and nursing staff.

Regulating pathway for bacterial diversities toward improved ecological benefits of thiencarbazone-methyl·isoxaflutole application: A field experiment.

Herbicide abuse has a significantly negative impact on soil microflora and further influences the ecological benefit. The regulating measures and corresponding mechanisms mitigating the decreased bacterial diversity due to herbicide use have rarely been studied. A field experiment containing the application gradient of an efficient maize herbicide thiencarbazone-methyl·isoxaflutole was performed. The relationship between soil bacterial community and thiencarbazone-methyl·isoxaflutole use was revealed. Modified attapulgite was added to explore its impacts on soil microflora under the thiencarbazone-methyl·isoxaflutole application. Based on the analytic network process-entropy weighting method-TOPSIS method model, the ecological benefit focusing on microbial responses was quantitatively estimated along with technical effectiveness and economic benefit. The results showed that the diversity indices of soil microflora, especially the Inv_Simpson index, were reduced at the recommended, 5 and 10 times the recommended dosages of thiencarbazone-methyl·isoxaflutole use. The Flavisolibacter bacteria was negatively correlated with the residues in soils based on the random forest model and correlation analysis, indicating a potential degrader of thiencarbazone-methyl·isoxaflutole residues. The structural equation model further confirmed that the high soil water content and soil pH promoted the function of Flavisolibacter bacteria, facilitated the dissipation of thiencarbazone-methyl·isoxaflutole residues and further improved the diversity of soil microflora. In addition, the presence of modified attapulgite was found to increase the soil pH, which may improve bacterial diversity through the regulating pathway. This explained the high ecological benefits of the treatment where the thiencarbazone-methyl·isoxaflutole was applied at the recommended dosage rates in conjunction with modified attapulgite addition. Therefore, the comprehensive benefits of thiencarbazone-methyl·isoxaflutole application with a focus on ecological benefits can be improved by regulating the soil pH with modified attapulgite.

Systematic Review and Meta-Analysis: Impact of Various Hemostasis Methods on Ovarian Reserve Function in Laparoscopic Cystectomy for Ovarian Endometriomas.

Background: Ovarian endometriomas, resulting from the invasion of endometriosis into ovarian tissue, can significantly affect ovarian reserve, potentially leading to infertility. When conservative treatments fail, it may further aggravate ovarian reserve decline by invading the ovarian cortex and, in severe cases, result in premature ovarian failure and infertility. Objective: This study aimed to investigate the impact of various hemostasis methods on ovarian reserve function in cases of laparoscopic cystectomy for ovarian endometriomas. Methods: We conducted a systematic review and meta-analysis to assess the effects of different hemostasis techniques used during laparoscopic cystectomy for ovarian endometriomas. A comprehensive analysis of relevant literature was performed, focusing on the impact of bipolar electrocoagulation, ultrasonic scalpel, and suture hemostasis on ovarian reserve function. The evaluation criteria included Anti-Müllerian hormone levels and antral follicle counts. Results: Our analysis revealed significant variations in the impact of hemostasis methods on ovarian reserve function. While all methods aimed to stop bleeding during surgery, the thermal damage to surrounding tissues differed. Bipolar electrocoagulation, ultrasonic scalpel, and suture hemostasis showed varying effects on ovarian reserve, with implications for post-operative fertility. Conclusions: The choice of the hemostasis method in laparoscopic cystectomy for ovarian endometriomas has a crucial influence on ovarian reserve function. Our findings emphasize the need to consider the potential consequences of thermal damage when selecting a hemostasis technique. Clinicians should weigh the benefits and risks of each method to protect ovarian reserve function effectively. This study offers valuable insights for guiding clinical practice, ensuring optimal outcomes for patients facing endometrioma-related fertility challenges.

Safe Rice Production in Cd-Contaminated Paddy Soil: Strategy and Environmental Implications.

This field study explored safe rice production in Cd-contaminated red paddy soil by application of the combined Si-/Se- containing foliar inhibitors (Si or Se) and the mixture amendments of quicklime (Q), polyacrylamide (A), or/and sepiolite (S) at low (1) and high (2) application rates. The results showed that all treatments increased soil pH and decreased total P and soil organic matter (excluding QSe2). With the increasing application rates, QAS significantly decreased the available Cd because of the enhanced stabilization, while QSi and QSe significantly increased the available Cd because of the inhibited plant uptake. After remediation, QA1, QSi2, and QSe2 most effectively decreased the uptake Cd by rice to meet the threshold of National Food Safety Standard of China. The treatments excluding Q1, QA1, QSi1, and QSi2 did not dramatically change the bacterial community structure in soil. Collectively, QSe2 was recommended for remediating Cd-contaminated red paddy soil.

The KDM6A-SPARCL1 axis blocks metastasis and regulates the tumour microenvironment of gastrointestinal stromal tumours by inhibiting the nuclear translocation of p65.

BACKGROUND: It is urgent to explore the pathogenic mechanism of gastrointestinal stromal tumours (GISTs). KDM6A, a histone demethylase, can activate gene transcription and has not been reported in GISTs. SPARCL1 may serve as a metastasis marker in GIST, but the molecular mechanism remains to be further explored. This study aimed to explore the biological function and molecular mechanism of KDM6A and SPARCL1 in GIST. METHODS: CCK-8, live cell count, colony formation, wound-healing and Transwell migration and invasion assays were employed to detect the cell proliferation, migration and invasion. A xenograft model and hepatic metastasis model were used to assess the role of KDM6A and SPARCL1 in vivo. RESULTS: KDM6A inhibited the proliferation, migration and invasion of GIST cells. Mechanistically, KDM6A promotes the transcription of SPARCL1 by demethylating histone H3 lysine trimethylation and consequently leads to the inactivation of p65. SPARCL1 affected the metastasis of GIST cells in a mesenchymal-epithelial transition- and matrix-metalloproteinase-dependent manner. SPARCL1 knockdown promoted angiogenesis, M2 polarisation and macrophage recruitment by inhibiting the phosphorylation of p65. Moreover, KDM6A and SPARCL1 inhibited hepatic metastasis and macrophage infiltration in vivo. CONCLUSIONS: Our findings establish the critical role of the KDM6A-SPARCL1-p65 axis in restraining the malignancy of GIST.

An Endoplasmic Reticulum Stress-MicroRNA-26a Feedback Circuit in NAFLD.

BACKGROUND AND AIMS: Endoplasmic reticulum (ER) stress is an adaptive response to excessive ER demand and contributes to the development of numerous diseases, including nonalcoholic fatty liver disease (NAFLD), which is hallmarked by the accumulation of lipid within hepatocytes. However, the underlying mechanisms remain elusive. MicroRNAs (miRNAs) play an indispensable role in various stress responses, but their implications in ER stress have not yet been systemically investigated. In this study, we identify a negative feedback loop consisting of hepatic ER stress and miR-26a in NAFLD pathogenesis. APPROACH AND RESULTS: Combining miRNA dot blot array and quantitative PCR, we find that miR-26a is specifically induced by ER stress in liver cells. This induction of miR-26a is critical for cells to cope with ER stress. In human hepatoma cells and murine primary hepatocytes, overexpression of miR-26a markedly alleviates chemical-induced ER stress, as well as palmitate-triggered ER stress and lipid accumulation. Conversely, deficiency of miR-26a exhibits opposite effects. Mechanistically, miR-26a directly targets the eukaryotic initiation factor 2α, a core ER stress effector controlling cellular translation. Intriguingly, miR-26a is reduced in the livers of patients with NAFLD. Hepatocyte-specific restoration of miR-26a in mice significantly mitigates high-fat diet-induced ER stress and hepatic steatosis. In contrast, deficiency of miR-26a in mice exacerbates high-fat diet-induced ER stress, lipid accumulation, inflammation and hepatic steatosis. CONCLUSIONS: Our findings suggest ER stress-induced miR-26a up-regulation as a regulator for hepatic ER stress resolution, and highlight the ER stress/miR-26a/eukaryotic initiation factor 2α cascade as a promising therapeutic strategy for NAFLD.

Positive and negative effects of nanoscale zero-valent iron-enriched biochar on sulfamethoxazole remediation in contaminated soil.

This study prepared surface-modified biochar, including acid washing biochar (HBC) and biochar supported with nanoscale zero-valent iron (nZVI-HBC). The surface-modified biochar was added to sulfamethoxazole (SMX)-contaminated soil with and without earthworms to examine the effects of surface-modified biochar and/or earthworms (Eisenia fetida) on the levels of SMX and its relevant genes (sul1, sul2, and intI1) in the soil. Additionally, the joint toxicity of these exogenous substances on earthworms was investigated. The results showed that although earthworms significantly enhanced the dissipation of SMX in the soils with and without HBC, this effect was not observed in the soil with nZVI-HBC. Among all treatments, nZVI-HBC most effectively accelerated SMX dissipation in the soil, regardless of coexisting earthworms. However, the presence of earthworms significantly increased the total relative abundances of sul1, sul2, and intI1 in the soil. A reasonable explanation for this is the shift in the bacterial community composition rather than the residual level of SMX. When earthworms coexisted, the richness of Proteobacteria evidently increased, which was the main host of the above genes. Both HBC and nZVI-HBC decreased these genes in the soil with earthworms, which was mainly due to the decrease in host genera from Proteobacteria, Actinobacteria, and Gemmatimonadetes. Although there was toxicity of single-surface-modified biochar or SMX on earthworms, the synergistic interaction of surface-modified biochar and SMX resulted in the most serious histopathological changes in earthworms and their highest superoxide dismutase activity.

Analysis of energy recovery and microbial community in an amalgamated CSTR-UASBs reactor for a three-stage anaerobic fermentation process of cornstalks.

In this study, a continuous stirred-tank reactor (CSTR) coupled with up-flow anaerobic sludge beds (UASBs) reactor was successfully developed for enhancing methane production and carbon recovery rate from cornstalks. Acetic acid production was higher in regions A than in B and C. The methane percentage achieved at 75.98% of total gas and methane production of cornstalks was up to 520.07 mL/g, during the stable operation period. The carbon of recovery rate, represented substrates converted to methane gas, reached 69.32% in stable stage. Microbial community structure analysis revealed that Paludibacter, Prevotella/Clostridium sensu stricto, and Caldisericum were the dominant bacteria for the degradation of cellulose, lignin, and other refractory macromolecules in regions A, B, and C, respectively. Methanobacterium and Methanolinea were the two major genera, accounting for methanogenesis generation.

Negative role of biochars in the dissipation and vegetable uptake of polycyclic aromatic hydrocarbons (PAHs) in an agricultural soil: Cautions for application of biochars to remediate PAHs-contaminated soil.

Biochars were studied for their impacts on the dissipation and vegetable uptake of polycyclic aromatic hydrocarbons (PAHs) in an agricultural soil. The health risks of PAHs taken up by vegetables were assessed by growing Chinese cabbage in both unamended soil and biochar-amended soils. In the unamended soil, the total 16 PAHs (Σ16PAHs) content decreased by 77.38% after planting the vegetable. The dissipation percentages of low-molecular-weight PAHs (LMW-PAHs), medium-molecular-weight PAHs (MMW-PAHs), and high-molecular-weight PAHs (HMW-PAHs) were 82.37%, 72.65%, and 68.63%, respectively. A significant negative correlation was determined between the dissipation percentages of PAHs in soil and the logKow of PAHs (p < 0.01), indicating that the affinity of PAHs for soil particles was one of an important limiting factors on the dissipation of PAHs. The uptake of PAHs by plant was significantly reduced with the increase in the molecular weight of the PAHs (76.55% for LWM-PAHs, 17.13% for MMW-PAHs, and 6.05% for HMW-PAHs). Addition of biochars to the soil decreased the dissipation of Σ16PAHs (73.59-77.01%), mostly due to a decrease in the dissipation of LMW-PAHs and MMW-PAHs. This finding was due to the immobilization of LMW-PAHs and MMW-PAHs within the biochar micropores. A marked reduction of Proteobacteria in biochar-amended soils also resulted in the decreased biodegradation of PAHs. Four of six biochars significantly increased the concentrations of Σ16PAHs in plant by 30.10-74.22%. Generally, biochars significantly increased the uptake of LMW-PAHs by plant but had little influence on the plant uptake of MMW-PAHs and HMW-PAHs. Three of six biochars notably increased the incremental lifetime cancer risk values based on the exposure of PAHs by vegetable consumption.

Perfluorinated compounds in a river basin from QingHai-Tibet Plateau: Occurrence, sources and key factors.

The occurrence of perfluorinated compounds (PFCs) in different environmental media in the QingHai-Tibet Plateau has been limitedly investigated. In this study, the water, sediments, soils and agricultural product samples were collected in the Huangshui River basin, and contents of the PFCs and values of water parameters were determined. This study investigated dominantly regulating factors of the distribution of PFCs in the water emphatically, explored the sources and assessed potential risks of the PFCs integrally. The results showed that perfluorohexanesulfonic acid, perfluorooctanesulfonic acid, perfluorobutanoic acid (PFBA) and perfluorooctanoic acid presented high maximum concentrations of 3207.42, 3015.96, 1941.89 and 826.4 ng L-1 in the water, respectively. There were 12 PFCs detected in crops, with the maximum concentration of 5206.86 ng g-1 for PFBA. The significantly positive correlation (p < 0.05) was observed between the concentrations of PFBA in crops and that in adjacent rivers, indicating that the irrigation most likely contributed to the accumulation of PFBA in the studied crops. The occurrence of the PFCs in the water during the dry season was dominantly regulated by fluorescent dissolved organic matters via the hydrophobic interaction, while it was primarily regulated by the total nitrogen and electrical conductivity via electrostatic interaction during the wet season. The PFCs in the water were mainly from the wastewater discharged from wastewater treatment plants and carpet factories, while the resuspension of the PFCs in sediments was also an important contribution especially in wet season. The PFCs in the river has posed sustained risk to the public health, especially children.

Clinical, surgical characteristics and long-term outcomes of lumbar hernia.

BACKGROUND/AIM: Lumbar hernia is caused by a defect in the abdominal wall. Due to its rarity, there is no established consensus on optimal treatment for lumbar hernia yet. Thus, we here investigated the clinical, surgical characteristics and outcomes of lumbar hernia by collecting 28 such patients from our hospital. METHODS: Patients diagnosed with lumbar hernia from our institution between April 2011 and August 2020 were retrospectively collected in this study. Demographics, clinical characteristics and surgical information were recorded. RESULTS: A consecutive series of 28 patients with lumbar hernia were retrospectively collected, including 13 males (46%) and 15 females (54%). The ages of the patients ranged from 5 to 79 years (median: 55 years), with a mean age of 55.6 ± 14.9 years. A total of 7 cases had a history of previous lumbar trauma or surgery. There were 11 (39%), 15 (54%) and 2 (7.1%) cases had right, left and bilateral lumbar hernia, respectively. Superior and inferior lumbar hernia were found in 25 (89%) and 3 (11%) patients. General anesthesia was adopted in 16 cases (group A), whereas 12 patients received local anesthesia (group B). Patients in the group B had a shorter hospital stay than that of the group A (3.5 ± 1.3 days vs. 7.1 ± 3.2 days, p = 0.001), as well as total hospitalization expenses between the two groups (2989 ± 1269 dollars vs. 1299 ± 229 dollars, p < 0.001). With a median follow-up duration of 45.9 months (range: 1-113 months), only 1 (3%) lumbar hernias recurred for the entire cohort. CONCLUSIONS: Lumbar hernia is a relatively rare entity, and inferior lumbar hernia is rarer. It is feasible to repair lumbar hernia under local anesthesia.

RNA G-quadruplex regulates microRNA-26a biogenesis and function.

BACKGROUND & AIMS: RNA G-quadruplexes (RG4s) appear to be important in post-transcriptional gene regulation, but their pathophysiological functions remain unknown. MicroRNA-26a (miR-26a) is emerging as a therapeutic target for various human diseases, however the mechanisms underlying endogenous miR-26a regulation are poorly understood. Herein, we study the role of RG4 in miR-26a expression and function in vitro and in vivo. METHODS: Putative RG4s within liver-enriched miRNAs were predicted by bioinformatic analysis, and the presence of an RG4 structure in the miR-26a-1 precursor (pre-miR-26a-1) was further analyzed by biophysical and biochemical methods. RG4 stabilizers, pre-miR-26a-1 overexpression plasmids, and luciferase reporter assays were used to assess the effect of RG4 on pre-miR-26a-1 maturation. Both miR-26a knock-in and knockout mouse models were employed to investigate the influence of this RG4 on miR-26a expression and function. Moreover, the interaction between RG4 in pre-miR-26a-1 and DEAH-box helicase 36 (DHX36) was determined by biophysical and molecular methods. Finally, miR-26a processing and DHX36 expression were quantified in the livers of obese mice. RESULTS: We identify a guanine-rich sequence in pre-miR-26a-1 that can fold into an RG4 structure. This RG4 impairs pre-miR-26a-1 maturation, resulting in a decrease in miR-26a expression and subsequently an increase in miR-26a cognate targets. In line with known miR-26a functions, this RG4 can regulate hepatic insulin sensitivity and lipid metabolism in vitro and in vivo. Furthermore, we reveal that DHX36 can bind and unwind this RG4 structure, thereby enhancing miR-26a maturation. Intriguingly, there is a concordant decrease of miR-26a maturation and DHX36 expression in obese mouse livers. CONCLUSIONS: Our findings define a dynamic DHX36/RG4/miR-26a regulatory axis during obesity, highlighting an important role of RG4 in physiology and pathology. LAY SUMMARY: Specific RNA sequences called G-quadruplexes (or RG4) appear to be important in post-transcriptional gene regulation. Obesity leads to the formation of these RG4 structures in pre-miR-26a-1 molecules, impairing the maturation and function of miR-26a, which has emerged as a therapeutic target in several diseases. This contributes to hepatic insulin resistance and the dysregulation of liver metabolism.

Immunomodulatory effect of oleoylethanolamide in dendritic cells via TRPV1/AMPK activation.

Oleoylethanolamide (OEA) is an endogenous lipid mediator involved in the control of feeding, body weight, and energy metabolism. However, whether OEA modulates maturation of dendritic cells (DCs) has never been addressed. Hence, we evaluated the effect of OEA on DCs maturation in bone marrow-derived DCs (BMDCs) in four aspects: (a) Cell surface markers were determined using flow cytometric analysis; (b) cell mobile ability was testified with the transwell assay; (c) stimulation of T cells proliferation was performed in a coculture system; and (d) cytokine production was measured using polymerase chain reaction (PCR). The result showed that, in mature BMDCs induced by lipopolysaccharides (LPS), the OEA treatment decreased expressions of cell surface markers, reduced cell migration, diminished the proliferation of cocultured T cells, and regulated cytokine production of BMDCs, indicating the modulatory effect of OEA on DCs maturation. Furthermore, to explore the underlying mechanism of the immunomodulatory effect of OEA, we used antagonists of transient receptor potential vanilloid-1 (TRPV1) and AMP-activated protein kinase (AMPK), determined the protein expressions of TRPV1/AMPK and Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) using western blot, and measured the intracellular calcium concentration using calcium imaging. The result illustrated that OEA downregulated TLR4/NF-κB, the classical pathway leading to DCs maturation induced by LPS, through the activation of TRPV1 and AMPK. Collectively, the present study suggests that OEA suppresses DCs maturation through the activation of TRPV1/AMPK. These findings increase our understanding of this endogenous lipid OEA.

cDNA cloning, prokaryotic expression and functional analysis of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) in Pogostemon cablin.

Pogostemon cablin is an important commercial source of patchouli oil, whose main active ingredient is patchouli alcohol. This sesquiterpene is a product of the mevalonate pathway, in which 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) is the rate-limiting enzyme. In this study, P. cablin HMGCR cDNA, comprising 2209 nucleotides encoding 425 amino acid residues was isolated, and bioinformatics analysis was used to analyze the protein sequence. Based on this analysis, a C-terminal truncated variant was engineered for recombinant expression in E. coli. The 38 kDa recombinant protein was identified by SDS-PAGE, and assayed for mevalonolactone production. According to the PcHMGCR1 gene sequence alignment with other species, the HMGCR protein had obvious resemblance with other plants HMG coenzyme A reductase and had homology with other species including plants, fungi, archaebacteria and animals. The prokaryotic expression vector was constructed by restriction enzyme digestion to be transformed into E. coli to express the recombinant protein, and 38 kDa recombinant protein was identified by the SDS-PAGE. Enzymatic activity was detected using GC-MS and, as a result, mevalonolactone was detected in the in vitro reaction mixture. Differential expression analysis showed that PcHMGCR1 expressed the highest amount in roots. The research results are of great significance for further research on the molecular biosynthesis mechanism of Patchouli alcohol in P. cablin.

Distribution of metal and metalloid elements in human scalp hair in Taiyuan, China.

This study investigated the levels of metal and metalloid elements (As, Ca, Cd, Cr, Cu, Fe, Hg, Mg, Ni, Pb, and Zn) in scalp hair samples collected from 161 people of different age and gender groups living in the six districts of Taiyuan, an industrial city with rich coal reserve in Shanxi province in China. Levels of most elements in the hair were high in the 26-40 age groups and increased with the length of residence. Calcium, Cr, Mg, Ni and Zn levels in the females' hair were significantly higher than those in the males' (p < 0.05). Element levels in the hair didn't have significantly differences between industrial and non-industrial districts because most of industry factories are in the upper wind position in Taiyuan, and contamination is prone to spread to non-industrial districts. The principal component analysis indicates that the main sources of these elements are mining activities, the neighboring stainless steel industry, and coal combustion. These results indicate that the industrial activities primarily contribute to the metal and metalloid pollution in Taiyuan, whereas numerous factors caused the metals accumulation in hair.

Multifunctional dendrimer-entrapped gold nanoparticles modified with RGD peptide for targeted computed tomography/magnetic resonance dual-modal imaging of tumors.

We report the use of multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) loaded with gadolinium (Gd) chelator/Gd(III) complexes and surface-modified with thiolated cyclo(Arg-Gly-Asp-Phe-Lys(mpa)) (RGD) peptide for targeted dual-mode computed tomography (CT)/magnetic resonance (MR) imaging of small tumors. In this study, amine-terminated generation 5 poly(amidoamine) dendrimers were used as a nanoplatform to be covalently modified with Gd chelator, RGD via a polyethylene glycol (PEG) spacer, and PEG monomethyl ether. Then the multifunctional dendrimers were used as templates to entrap gold nanoparticles, followed by chelating Gd(III) ions and acetylation of the remaining dendrimer terminal amines. The thus-formed multifunctional Au DENPs (in short, Gd-Au DENPs-RGD) were characterized via different techniques. We show that the multifunctional Au DENPs with a Au core size of 3.8 nm are water-dispersible, stable under different pH (5-8) and temperature conditions (4-50 °C), and noncytotoxic at a Au concentration up to 100 µM. With the displayed X-ray attenuation property and the r1 relaxivity (2.643 mM(-1) s(-1)), the developed Gd-Au DENPs-RGD are able to be used as a dual-mode nanoprobe for targeted CT/MR imaging of an αvß3 integrin-overexpressing xenografted small tumor model in vivo via RGD-mediated active targeting pathway. The developed multifunctional Gd-Au DENPs-RGD may be used as a promising dual-mode nanoprobe for targeted CT/MR imaging of different types of αvß3 integrin-overexpressing cancer.

Dendrimer-Assisted Formation of Fe3O4/Au Nanocomposite Particles for Targeted Dual Mode CT/MR Imaging of Tumors.

A unique dendrimer-assisted approach is reported to create Fe3O4/Au nanocomposite particles (NCPs) for targeted dual mode computed tomography/magnetic resonance (CT/MR) imaging of tumors. In this approach, preformed Fe3O4 nanoparticles (NPs) are assembled with multilayers of poly(γ-glutamic acid) (PGA)/poly(L-lysine)/PGA/folic acid (FA)-modified dendrimer-entrapped gold nanoparticles via a layer-by-layer self-assembly technique. The interlayers are crosslinked via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide chemistry, the assembled Au core NPs are then used as seed particles for subsequent seed-mediated growth of Au shells via iterative Au salt reduction process, and subsequent acetylation of the remaining amines of dendrimers leads to the formation of Fe3O4/Au(n.)Ac-FA NCPs with a tunable molar ratio of Au/Fe3O4. It is shown that the Fe3O4/Au(n.)Ac-FA NCPs at an optimized Au/Fe3O4 molar ratio of 2.02 display a relatively high R2 relaxivity (92.67 × 10(-3) M(-1) s(-1)) and good X-ray attenuation property, and are cytocompatible and hemocompatible in the given concentration range. Importantly, with the FA-mediated targeting, the Fe3O4/Au(n.)Ac-FA NCPs are able to be specifically uptaken by cancer cells overexpressing FA receptors, and be used as an efficient nanoprobe for targeted dual mode CT/MR imaging of a xenografted tumor model. With the versatile dendrimer chemistry, the developed Fe3O4/Au NCPs may be differently functionalized, thereby providing a unique platform for diagnosis and therapy of different biological systems.

[Magnetic resonance guided focused ultrasound surgery for pain palliation of bone metastases: early experience of clinical application in China].

OBJECTIVE: To evaluate the safety and efficacy of magnetic resonance guided focused ultrasound surgery (MRgFUS) in treatment for pain palliation of bone metastases. METHODS: Eighty-one patients of painful bone metastases were volunteered to screen for this study in Shanghai General Hospital from June 2014 to February 2015. Twenty-three patients among them were treated by MRgFUS, who was more than 18-years old, having the ability to fully understand the informed consent of the research, suffering with pain of numeric rating scale (NRS) ≥ 4, non-received radiotherapy or chemotherapy for pain palliation of bone metastases in the past two weeks. The NRS, the standard question of Brief Pain Inventory (BPI-QoL), and the standard question of Europe Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Bone Metastases 22 (EORTC QLQ-BM22) were respectively recorded before and 1-week, 1-month, 3-month after the treatment. The related adverse events of MRgFUS were observed and recorded in 3 months after the treatment as well. RESULTS: (1)Twenty-three metastatic bone tumor lesions of 23 patients were treated by MRgFUS, the treatment data was as follows: the mean treatment time was (88 ± 33) minutes, the mean sonication number was 13 ± 8. (2) Adverse events included: pain in therapy area 3/23, which spontaneous relieving within one week; numbness in lower limb (1/23), which relieved after physiotherapy. (3) The NRS of before treatment and at 1-week, 1-month, and 3-month after treatment respectively was 6.0 ± 1.5, 3.7 ± 1.7,3.1 ± 2.0, and 2.2 ± 1.0,which significantly decreased after the treatment (P<0.01). (4) The BPI-QoL score of before treatment and at 1-week, 1-month, and 3-month after treatment respectively was 39 ± 16, 27 ± 18, 26 ± 18, and 21 ± 18, which significantly decreased after the treatment (P<0.01). (5) The EORTC QLQ-BM22 score of before treatment and at 1-week, 1-month, and 3-month after treatment respectively was 52 ± 13, 44 ± 12, 42 ± 12, and 39 ± 12, which also significantly decreased after the treatment (P<0.01). CONCLUSIONS: MRgFUS can be used as a non-invasive, safe, and effective method for treating painful bone metastases. Its clinical benefits of pain palliation and patient's quality of life improving are sustained after the treatment at least to 3 months.