Development and Validation of a Fusion Model Based on Carotid Plaques and White Matter Lesion Burden Imaging Characteristics to Evaluate Ischemic Stroke Severity in Symptomatic Patients.

BACKGROUND: The diagnostic value of carotid plaque characteristics based on higher-resolution vessel wall MRI (HRVW-MRI) combined with white matter lesion (WML) burden for the risk of ischemic stroke is unclear. PURPOSE: To combine carotid plaque features and WML burden to construct a hybrid model for evaluating ischemic stroke severity and prognosis in patients with symptomatic carotid artery stenosis. STUDY TYPE: Retrospective. SUBJECTS: One hundred and ninty-three patients with least one confirmed carotid atherosclerotic stenosis ≥30% and cerebrovascular symptoms within the last 2 weeks (136 in the training cohort and 57 in the test cohort). FIELD STRENGTH/SEQUENCE: 3.0T, T2-weighted fluid attenuated inversion recovery (T2-FLAIR) and diffusion-weighted imaging (DWI); HRVW-MRI: 3D T1-weighted variable flip angle fast spin-echo sequences (VISTA), T2-weighted VISTA, simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP), and contrast-enhanced T1-VISTA. ASSESSMENT: The following features of the plaques or vessel wall were assessed by three MRI readers independently: calcification (CA), intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), ulceration, plaque enhancement (PE), maximum vessel diameter (Max VD), maximum wall thickness (Max WT), total vessel area (TVA), lumen area (LA), plaque volume, and lumen stenosis. WMLs were graded visually and categorized as absent-to-mild WMLs (Fazekas score 0-2) or moderate-severe WMLs (Fazekas score 3-6). WML volumes were quantified using a semiautomated volumetric analysis program. Modified Rankin scores (mRS) were assessed at 90 days, following an outpatient interview, or by telephone. STATISTICAL TESTS: LASSO-logistic regression analysis was performed to construct a model. The performance of the model was evaluated using receiver operating characteristic (ROC) curve analyses, calibration curves, decision curve analyses, and clinical imaging curves. Conditional logistic regression analysis was used to explore the associations between the hybrid model-derived score and the modified Rankin Scale (mRS) score at 90 days. RESULTS: The model was constructed using five selected features, including IPH, plaque enhancement, ulceration, NWI, and total Fazekas score in deep WMLs (DWMLs). The hybrid model yielded an area under the curve of 0.92 (95% confidence interval [CI] 0.87-0.97) in the training cohort and 0.88 (0.80-0.96) in the test cohort. Furthermore, the hybrid model-derived score (odds ratio = 1.28; 95% CI 1.06-1.53) was independently associated with the mRS score 90 days after stroke. DATA CONCLUSIONS: The hybrid model constructed using MRI plaque characteristics and WML burden has potential to be an effective noninvasive method of assessing ischemic stroke severity. The model-derived score has promising utility in judging neurological function recovery. TECHNICAL EFFICACY: Stage 2.

MIL-101(CuFe) Nanozymes with Excellent Peroxidase-like Activity for Simple, Accurate, and Visual Naked-Eye Detection of SARS-CoV-2.

The COVID-19 pandemic has spread to every corner of the world and seriously affected our health and daily activities in the past three years; thereby, it is still urgent to develop various simple, quick, and accurate methods for early detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Nanozymes, a kind of nanomaterial with intrinsic enzyme-mimicking activity, have emerged as a suitable alternative for both therapy and diagnosis of SARS-CoV-2. Here, ultrasensitive and ultrafast MIL-101(CuFe)-CD147 biosensors are established for the detection of SARS-CoV-2 by a simple colorimetric method. A MIL-101(CuFe) metal-organic framework has excellent peroxidase-like activity due to the synergistic effect of Fe and Cu atoms. In addition, the MIL-101(CuFe)-CD147 biosensor shows great potential to detect the various variants of SARS-CoV-2 due to the universal receptor of CD147. The enzyme-based biosensor for the detection of SARS-CoV-2 achieves a very low limit of detection (about 3 PFU/mL) within 30 min. Therefore, the present method provides a new generation of an alternative approach for highly sensitive and visual diagnosis of COVID-19.

New insights into the origin of buckwheat cultivation in southwestern China from pollen data.

Buckwheat is an important crop which originated in China and spread widely across Eurasia. However, exactly where in China domestication took place remains controversial. Archaeological and palynological records suggest a longer cultivation history of buckwheat in northern China than in southwestern China, but this conflicts with phylogenetic evidence implicating southwestern China as the centre of origin and diversity of buckwheat. We investigate alternative methodologies for inferring the occurrence of buckwheat cultivation and suggest that relative abundance could provide a reliable measure for distinguishing between wild and cultivated buckwheat in both present-day and fossil samples. Approximately 12 800-yr palaeoecological record shows that Fagopyrum pollen occurred only infrequently before the early Holocene. As southwestern China entered the early agricultural period, c. 8000-7000 yr ago, a slight increase in abundance of Fagopyrum pollen was observed. Approximately 4000 yr ago, concurrent with the Pu minority beginning to develop dry-land agriculture, the abundance of Fagopyrum pollen increased significantly, suggesting the cultivation of this crop. Fagopyrum pollen rose to a maximum value c. 1270 yr ago, suggesting an intensification of agricultural activity. These findings fill a gap in the Fagopyrum pollen record in southwestern China and provide new indications that early cultivation may have occurred in this region.

CRISPR/Cas9 and Agrobacterium tumefaciens virulence proteins synergistically increase efficiency of precise genome editing via homology directed repair in plants.

CRISPR/Cas9 genome editing and Agrobacterium tumefaciens-mediated genetic transformation are widely-used plant biotechnology tools derived from bacterial immunity-related systems, each involving DNA modification. The Cas9 endonuclease introduces DNA double-strand breaks (DSBs), and the A. tumefaciens T-DNA is released by the VirD2 endonuclease assisted by VirDl and attached by VirE2, transferred to the plant nucleus and integrated into the genome. Here, we explored the potential for synergy between the two systems and found that Cas9 and three virulence (Vir) proteins achieve precise genome editing via the homology directed repair (HDR) pathway in tobacco and rice plants. Compared with Cas9T (Cas9, VirD1, VirE2) and CvD (Cas9-VirD2) systems, the HDR frequencies of a foreign GFPm gene in the CvDT system (Cas9-VirD2, VirD1, VirE2) increased 52-fold and 22-fold, respectively. Further optimization of the CvDT process with a donor linker (CvDTL) achieved a remarkable increase in the efficiency of HDR-mediated genome editing. Additionally, the HDR efficiency of the three rice endogenous genes ACETOLACTATE SYNTHASE (ALS), PHYTOENE DESATURASE (PDS), and NITROGEN TRANSPORTER 1.1 B (NRT1.1B) increased 24-, 32- and 16-fold, respectively, in the CvDTL system, compared with corresponding Cas9TL (Cas9T process with a donor linker). Our results suggest that collaboration between CRISPR/Cas9 and Agrobacterium-mediated genetic transformation can make great progress towards highly efficient and precise genome editing via the HDR pathway.

Preoperative Assessment of Blood Vessels and Intratumoral Microbleeds in Brain Tumors Based on a 3D Contrast-Enhanced T1 -Weighted Flow-Sensitive Black-Blood Sequence.

BACKGROUND: Three-dimensional (3D) contrast-enhanced T1 -weighted flow-sensitive black-blood (CE-T1 WI FSBB) is a newly developed black blood sequence by adding motion probing gradient pulses to gradient echo (GRE) sequences, which has important value for the preoperative assessment of tumor brain blood supply vessels and intratumoral microbleeds. PURPOSE: To compare 3D CE-T1 WI FSBB and 3D contrast-enhanced fast spin echo (FSE) sequence for T1 WI for preoperative assessment of blood vessels and microbleeds in brain tumors and to investigate the correlation between visible vessels and microbleeds. STUDY TYPE: Prospective. SUBJECTS: One hundred and seventy-five patients with brain tumors, 65 were male, 110 were female. Including histologically confirmed 73 meningiomas, 23 schwannomas, 20 gliomas, 7 hemangioblastomas, 5 metastases, 2 lymphomas, 2 hemangiopericytomas, 2 germ cell tumors, 1 craniopharyngioma, and 1 cholesteatoma. FIELD STRENGTH/SEQUENCE: A 3-T, CE-T1 WI FSBB, GRE; 3-T, CE-T1 WI, FSE. ASSESSMENT: Three neuroradiologists counted the number of intratumoral vessels on CE-T1 WI and CE-T1 WI FSBB images separately, and they counted the number of intratumoral microbleeds on CE-T1 WI FSBB images. Brain tumors were classified into grade I, grade II, and grade IV according to the World Health Organization (WHO) grading. Differences in the ability of CE-T1 WI FSBB and CE-T1 WI to display intratumoral vessels were compared. The mean counts of three observers were used to study the correlation between vessels and microbleeds. STATISTICAL TESTS: Two-way random intraclass correlation coeficient (ICC) was used for inter-reader agreement regarding intratumoral vessel and microbleed counts, and the linear regression analysis (with F-test) was used to study the correlation between intratumoral vessels and microbleeds based on CE-T1 WI FSBB (α = 0.05). RESULTS: Inter-reader agreements for intratumoral vessel count on CE-T1 WI (ICC = 0.93) and CE-T1 WI FSBB (ICC = 0.92), and the agreement for intratumoral microbleed count on CE-T1 WI FSBB (ICC = 0.99) were excellent. There were statistically significant differences in intratumoral vessel counts between CE-T1 WI and CE-T1 WI FSBB using Mann-Whitney U -test: image readers could identify more intratumoral vessels on CE-T1 WI FSBB images, particularly for meningiomas, schwannomas, gliomas, and WHO grade I tumors. The number of intratumoral vessels had a significant positive effect on the number of intratumoral microbleeds (microbleeds = 5.024 + 1.665 × vessels; F = 11.51). DATA CONCLUSION: More intratumoral vessels could potentially be identified using a 3D CE-T1 WI FSBB sequence compared to a CE-T1 WI sequence, and the number of intratumoral vessels showed a positive linear relationship with the number of intratumoral microbleeds, which might suggest that brain tumors with rich blood supply were more prone to intratumoral microbleeds. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Insights into the Selective Transformation of Ceria Sulfation and Iron/Manganese Mineralization for Enhancing the Selective Recovery of Rare Earth Elements.

To cope with the urgent and unprecedented demands for rare earth elements (REEs) in sophisticated industries, increased attention has been paid to REE recovery from recycled streams. However, the similar geochemical behaviors of REEs and transition metals often result in poor separation performance due to nonselectivity. Here, a unique approach based on the selective transformation between ceria sulfation and iron/manganese mineralization was proposed, leading to the enhancement of the selective separation of REEs. The mechanism of the selective transformation of minerals could be ascribed to the distinct geochemical and metallurgical properties of ions, resulting in different combinations of cations and anions. According to hard-soft acid-base (HSAB) theory, the strong Lewis acid of Ce(III) was inclined to combine with the hard base of sulfates (SO42-), while the borderline acid of Fe(II)/Mn(II) prefers to interact with oxygen ions (O2-). Both in situ characterization and density functional theory (DFT) calculation further revealed that such selective transformation might trigger by the generation of an oxygen vacancy on the surface of CeO2, leading to the formation of Ce2(SO4)3 and Fe/Mn spinel. Although the electron density difference of the configurations (CeO2-x-SO4, Fe2O3-x-SO4, and MnO2-x-SO4) shared a similar direction of the electron transfer from the metals to the sulfate-based oxygen, the higher electron depletion of Ce (QCe = -1.91 e) than Fe (QFe = -1.66 e) and Mn (QMn = -1.64 e) indicated the higher stability in the Ce-O-S complex, resulting in the larger adsorption energy of CeO2-x-SO4 (-6.88 eV) compared with Fe2O3-x-SO4 (-3.10 eV) and MnO2-x-SO4 (-2.49 eV). This research provided new insights into the selective transformation of REEs and transition metals in pyrometallurgy and thus offered a new approach for the selective recovery of REEs from secondary resources.

New Insights into the Role of Natural Organic Matter in Fe-Cr Coprecipitation: Importance of Molecular Selectivity.

Coprecipitation of Fe/Cr hydroxides with natural organic matter (NOM) is an important pathway for Cr immobilization. However, the role of NOM in coprecipitation is still controversial due to its molecular heterogeneity and diversity. This study focused on the molecular selectivity of NOM toward Fe/Cr coprecipitates to uncover the fate of Cr via Fourier transform-ion cyclotron resonance-mass spectrometry (FT-ICR-MS). The results showed that the significant effects of Suwannee River NOM (SRNOM) on Cr immobilization and stability of the Fe/Cr coprecipitates did not merely depend on the adsorption of SRNOM on Fe/Cr hydroxides. FT-ICR-MS spectra suggested that two pathways of molecular selectivity of SRNOM in the coprecipitation affected Cr immobilization. Polycyclic aromatics and polyphenolic compounds in SRNOM preferentially adsorbed on the Fe/Cr hydroxide nanoparticles, which provided extra binding sites and promoted the aggregation. Notably, some specific compounds (i.e., polyphenolic compounds and highly unsaturated phenolic compounds), less unsaturated and more oxygenated than those adsorbed on Fe/Cr hydroxide nanoparticles, were preferentially incorporated into the insoluble Cr-organic complexes in the coprecipitates. Kendrick mass defect analysis revealed that the insoluble Cr-organic complexes contained fewer carbonylated homologous compounds. More importantly, the spatial distribution of insoluble Cr-organic complexes was strongly related to Cr immobilization and stability of the Fe/Cr-NOM coprecipitates. The molecular information of the Fe/Cr-NOM coprecipitates would be beneficial for a better understanding of the transport and fate of Cr and exploration of the related remediation strategy.

Plasma-Membrane-Localized Transporter NREET1 is Responsible for Rare Earth Element Uptake in Hyperaccumulator Dicranopteris linearis.

Rare earth elements (REEs) are critical for numerous modern technologies, and demand is increasing globally; however, production steps are resource-intensive and environmentally damaging. Some plant species are able to hyperaccumulate REEs, and understanding the biology behind this phenomenon could play a pivotal role in developing more environmentally friendly REE recovery technologies. Here, we identified a REE transporter NRAMP REE Transporter 1 (NREET1) from the REE hyperaccumulator fern Dicranopteris linearis. Although NREET1 belongs to the natural resistance-associated macrophage protein (NRAMP) family, it shares a low similarity with other NRAMP members. When expressed in yeast, NREET1 exhibited REE transport capacity, but it could not transport divalent metals, such as zinc, nickel, manganese, or iron. NREET1 is mainly expressed in D. linearis roots and predominantly localized in the plasma membrane. Expression studies in Arabidopsis thaliana revealed that NREET1 functions as a transporter mediating REE uptake and transfer from root cell walls into the cytoplasm. Moreover, NREET1 has a higher affinity for transporting light REEs compared to heavy REEs, which is consistent to the preferential enrichment of light REEs in field-grown D. linearis. We therefore conclude that NREET1 may play an important role in the uptake and consequently hyperaccumulation of REEs in D. linearis. These findings lay the foundation for the use of synthetic biology techniques to design and produce sustainable, plant-based REE recovery systems.

Indicator species drive the key ecological functions of microbiota in a river impacted by acid mine drainage generated by rare earth elements mining in South China.

Acid mine drainage (AMD) generated by rare earth elements (REEs) deposits exploration contains high concentrations of REEs, ammonium and sulfates, which is quite different from typical metallic AMD. Currently, microbial responses and ecological functions in REEs-AMD impacted rivers are unknown. Here, 16S rRNA analysis and genome-resolved metagenomics were performed on microbial community collected from a REEs-AMD contaminated river. The results showed that REEs-AMD significantly changed river microbial diversity and shaped unique indicator species (e.g. Thaumarchaeota, Methylophilales, Rhodospirillales and Burkholderiales). The main environmental factors regulating community were pH, ammonium and REEs, among which high concentration of REEs increased REEs-dependent enzyme-encoding genes (XoxF and ExaF/PedH). Additionally, we reconstructed 566 metagenome-assembled genomes covering 70.4% of identifying indicators. Genome-centric analysis revealed that the abundant archaea Thaumarchaeota and Xanthomonadaceae were often involved in nitrification and denitrification, while family Burkholderiaceae were capable of sulfide oxidation coupled with dissimilatory nitrate reduction to ammonium. These indicators play crucial roles in nitrogen and sulfur cycling as well as REEs immobilization in REEs-AMD contaminated rivers. This study confirmed the potential dual effect of REEs on microbial community at the functional gene level. Our investigation on the ecological roles of indicators further provided new insights for the development of REEs-AMD bioremediation.

Discrimination and Quantification of Soil Nanoparticles by Dual-Analyte Single Particle ICP-QMS.

This study presents the new application of dual-analyte single particle inductively coupled plasma quadrupole mass spectrometry (spICP-QMS) to the discrimination and quantification of two typical soil nanoparticles (kaolinite and goethite nanoparticles, abbr. KNPs and GNPs) in three samples (SA, SB, and SC) with three detection events (Al unpaired event, Fe unpaired event, and paired event). SA was mainly composed of KNPs with a concentration of 28 443 ± 817 particle mL-1 and a mean particle size of 140.7 ± 0.2 nm. SB was mainly composed of GNPs with a concentration of 39 283 ± 702 particle mL-1 and a mean particle size of 141.8 ± 2.9. In SC, the concentrations of KNPs and GNPs were 22 4541 ± 1401 and 70 604 ± 1623 particle mL-1, respectively, and the mean particle sizes of KNPs and GNPs were 140.7 ± 0.2 and 60.2 ± 0.3 nm, respectively. The accuracy of dual-analyte spICP-QMS was determined by spiking experiments, comparing these results with the measurements of other techniques, analyzing the samples in different SA and SB proportions and in different SC concentrations. Our results demonstrated that the dual-analyte spICP-QMS is a promising approach to distinguishing different kinds of natural NPs in soils.

A Bridge to Alkaloid Synthesis.

The construction of a structurally rigid architecture with chiral complexity, necessary to enhance the interaction with binding sites of drug targets, has been adapted as an intriguing approach in drug development. In the past few years, we have been interested in the synthesis of biologically significant and bridged alkaloids via novel synthetic methods and strategies based on recognition of the privileged pattern. Therefore, nitroso-ene and aza-Wacker cyclizations were elevated for the first time to construct bridged alkaloids, such as hosieine A, kopsone, melinonine-E and strychnoxanthine. Mechanistic investigations, including computational calculations for nitroso-ene reaction and deuterated experiments for aza-Wacker reaction, enable us to gain more insights into the chemical reactivity and selectivity of specific functional groups in developing viable synthetic methods.

Chalcone derivatives ameliorate lipopolysaccharide-induced acute lung injury and inflammation by targeting MD2.

Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are known as the common causes of respiratory failure in critically ill patients. Myeloid differentiation 2 (MD2), a co-receptor of toll like receptor 4 (TLR4), plays an important role in LPS-induced ALI in mice. Since MD2 inhibition by pharmacological inhibitors or gene knockout significantly attenuates ALI in animal models, MD2 has become an attractive target for the treatment of ALI. In this study we identified two chalcone-derived compounds, 7w and 7x, as new MD2 inhibitors, and investigated the therapeutic effects of 7x and 7w in LPS-induced ALI mouse model. In molecular docking analysis we found that 7w and 7x, formed pi-pi stacking interactions with Phe151 residue of the MD2 protein. The direct binding was confirmed by surface plasmon resonance analysis (with KD value of 96.2 and 31.2 µM, respectively) and by bis-ANS displacement assay. 7w and 7x (2.5, 10 µM) also dose-dependently inhibited the interaction between lipopolysaccharide (LPS) and rhMD2 and LPS-MD2-TLR4 complex formation. In mouse peritoneal macrophages, 7w and 7x (1.25-10 µM) dose-dependently inhibited LPS-induced inflammatory responses, MAPKs (JNK, ERK and P38) phosphorylation as well as NF-κB activation. Finally, oral administration of 7w or 7x (10 mg ·kg-1 per day, for 7 days prior LPS challenge) in ALI mouse model significantly alleviated LPS-induced lung injury, pulmonary edema, lung permeability, inflammatory cells infiltration, inflammatory cytokines expression and MD2/TLR4 complex formation. In summary, we identify 7w and 7x as new MD2 inhibitors to inhibit inflammatory response both in vitro and in vivo, proving the therapeutic potential of 7w and 7x for ALI and inflammatory diseases.

Green tea polyphenols inhibit malignant melanoma progression via regulating circ_MITF/miR-30e-3p/HDAC2 axis.

Green tea polyphenols (GTPs) are regarded as anticancer substances and have been revealed to play significant roles in the development of malignant melanoma. However, the mechanisms by which GTPs perform anticarcinogenic activity are not well elucidated. Cellular function assays revealed that GTPs inhibited melanoma cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted apoptosis in vitro. Circ_MITF expression was elevated in melanoma tissues and cells but was decreased by GTPs in cells. Functional experiments indicated circ_MITF overexpression reversed the anticancer effects of GTPs on melanoma cells. Then the underlying mechanism analysis suggested that circ_MITF served as a sponge for miR-30e-3p to upregulate the level of HDAC2. MiR-30e-3p reexpression attenuated the regulatory effects of circ_MITF on GTPs-treated melanoma cells. Silencing of miR-30e-3p promoted the malignant phenotypes in GTPs-treated melanoma cells, which were reversed by HDAC2 knockdown. Preclinically, administration of GTPs suppressed the expression of downstream target genes and repressed tumorigenesis of xenografts in nude mice. In all, GTPs suppressed melanoma progression by regulating circ_MITF/miR-30e-3p/HDAC2 axis, providing a potential therapeutic strategy for human malignant melanoma intervention.

Characterization of Neodymium Speciation in the Presence of Fulvic Acid by Ion Exchange Technique and Single Particle ICP-MS.

It has been well known that the free ion concentration of metals plays a vital role in metal bioavailability. However, measurement of this fraction is still not easy over years of development. Nowadays, rare earth elements (REEs) are drawing more attentions as an emerging contaminant due to their wide applications in our daily life. To analyze the free ion concentration of neodymium (Nd), we adopted ion-exchange technique (IET) to investigate the changes on Nd free ion concentration in the presence of fulvic acid (FA). With the dynamic mode of IET analysis, the concentrations of Nd free ion were in the range of 0.85-36.8 × 10-8 M at the total Nd concentration of 5 × 10-7 M when FA varied from 0.4 to 10 M. However, these concentrations were 3-58 times higher than the one calculated by WHAM 7.0, which may be due to the particulate Nd spontaneously formed in solution. With single particle ICP-MS analysis, we found 0.25%-2.36% of Nd was in the form of colloids when the total Nd concentrations varied from 8.5 × 10-9 to 4.7 × 10-7 M, with the average particle sizes in the range of 26.5-39.2 nm. The presence of FA significantly decreased the number of Nd colloids, but increased the average particle size. Under the TEM, we found that Nd colloids were amorphous, with the size less than 200 nm. The present study provided a relatively new perspective on REE speciation in water. The natural organic matters not only affect the free ion concentration of Nd, but also influenced the size and numbers of Nd colloids in solution.

Roles of soluble minerals in Cd sorption onto rice straw biochar.

Transforming to biochar provides an environmentally friendly approach for crop residue reutilization, which are usually applied as sorbent for heavy metal removal. As typical silicon-rich material, the specific sorptive mechanisms of rice straw derived biochar (RSBC) are concerned, especially at the low concentration range which is more environmentally relevant. In the present study, Cd sorption onto RSBCs at the concentration of ≤ 5 mg/L was investigated. The sorptive capacity was positively correlated with the pyrolytic temperature of the biochar and the environmental pH value. Water soluble minerals of the RSBCs played the dominant roles in Cd sorption, contributing 29.2%, 62.5% and 82.9% of the total sorption for RSBCs derived under 300°C, 500°C and 700°C, respectively. Increased number of cations, dominantly K+, were exchanged during the sorption. Coprecipitation with cations and carbonates may also be contributive to the sorption. The dissolution of silicon-containing minerals was found to be declined during sorption, suggesting its involvement in the sorption process, possibly through precipitation. Whilst, the sparingly soluble silicate crystals may impose ignorable role in the sorption. Complexation with organic groups is only a minor mechanism in Cd sorption, compared to the much more dominant roles of the inorganic ashes.

Rare earth elements, aluminium and silicon distribution in the fern Dicranopteris linearis revealed by µPIXE Maia analysis.

BACKGROUND: The fern Dicranopteris linearis is a hyperaccumulator of rare earth elements (REEs), aluminium (Al) and silicon (Si). However, the physiological mechanisms of tissue-level tolerance of high concentrations of REE and Al, and possible interactions with Si, are currently incompletely known. METHODS: A particle-induced X-ray emission (µPIXE) microprobe with the Maia detector, scanning electron microscopy with energy-dispersive spectroscopy and chemical speciation modelling were used to decipher the localization and biochemistry of REEs, Al and Si in D. linearis during uptake, translocation and sequestration processes. RESULTS: In the roots >80 % of REEs and Al were in apoplastic fractions, among which the REEs were most significantly co-localized with Si and phosphorus (P) in the epidermis. In the xylem sap, REEs were nearly 100 % present as REEH3SiO42+, without significant differences between the REEs, while 24-45 % of Al was present as Al-citrate and only 1.7-16 % Al was present as AlH3SiO42+. In the pinnules, REEs were mainly concentrated in necrotic lesions and in the epidermis, and REEs and Al were possibly co-deposited within phytoliths (SiO2). Different REEs had similar spatial localizations in the epidermis and exodermis of roots, the necrosis, veins and epidermis of pinnae of D. linearis. CONCLUSIONS: We posit that Si plays a critical role in REE and Al tolerance within the root apoplast, transport within the vascular bundle and sequestration within the blade of D. linearis.

Structurally diverse biflavonoids from the fruits of Citrus medica L. var. sarcodactylis Swingle and their hypolipidemic and immunosuppressive activities.

The fruit of Citrus medica L. var. sarcodactylis Swingle is not only used as a traditional medicinal plant, but also served as a delicious food. Six new (3'→7″)-biflavonoids (1-6), and twelve known biflavonoid derivatives (7-18) were isolated and characterized from the fruits of C. medica L. var. sarcodactylis Swingle for the first time. Their structures were determined by extensive and comprehensive analyzing NMR, HR-ESI-MS, UV, and IR spectral data coupled with the data described in the literature. Compounds (1-18) were evaluated for their hypolipidemic activities with Orlistat as the positive control, and assayed for their immunosuppressive activities with Dexamethasone as the positive control, respectively. Among them, compounds (1-3) exhibited moderate inhibition of pancreatic lipase activity by inhibiting 68.56 ± 1.40%, 56.18 ± 1.57%, 53.51 ± 1.59% of pancreatic lipase activities at the concentration of 100 µM, respectively. Compounds (4-6) and 8 showed potent immunosuppressive activities with the IC50 values from 16.83 ± 1.32 to 50.90 ± 1.79 µM. The plausible biogenetic pathway and preliminary structure activity relationship of the selected compounds were scientifically summarized and discussed in this study.

[Prenatal diagnosis and genetic counseling in 19 cases with 22q11.2 microduplications].

OBJECTIVE: Patients with 22q11.2 microduplications have highly variable clinical phenotypes. The clinical manifestations and prognosis of 19 fetuses carrying 22q11.2 microduplications were analyzed. METHODS: The fetuses were analyzed by single nucleotide polymorphism array (SNP array), which was followed by parental validation. Pregnancy outcome and clinical features of the newborns were analyzed in order to delineate genotype-phenotype correlation. RESULTS: Two fetuses were identified by karyotyping analysis of amniotic fluid samples. SNP array revealed that all have carried a 468.8 kb~3.4 Mb duplication in 22q11.2 region. Two couples have refused parental verification. Seven cases were inherited from the mother, 6 were from the father, and 4 cases were de novo in origin. Three couples opted termination of the pregnancy. One fetus perished at birth. Five newborns showed delayed growth, the remaining 10 were normal. CONCLUSION: The prenatal phenotype of fetuses carrying 22q11.2 microduplications are nonspecific, and the phenotypes of survivors may become more diverse along with increased age. Professional evaluation and long-term follow-up should be recommended.

The Cotton miR477-CBP60A Module Participates in Plant Defense Against Verticillium dahlia.

Previous reports have shown that, when Verticillium dahliae localizes at the root surface, many microRNAs (miRNAs) were identified at the early induction stage. Here, we constructed two groups from two timepoints of small RNA (sRNA) in cotton root responses to V. dahliae at the later induction stage, pathogen localizing in the interior of root tissue. We identified 71 known and 378 novel miRNAs from six libraries of the pathogen-induced and the control sRNAs. Combined with degradome and sRNA sequencing, 178 corresponding miRNA target genes were identified, in which 40 target genes from differentially expressed miRNAs were primarily associated with oxidation-reduction and stress responses. More importantly, we characterized the cotton miR477-CBP60A module in the later response of the plant to V. dahliae infection. A ß-glucuronidase fusion reporter and cleavage site analysis showed that ghr-miR477 directly cleaved the messenger RNA of GhCBP60A in the posttranscriptional process. The ghr-miR477-silencing decreased plant resistance to this fungus, while the knockdown of GhCBP60A increased plant resistance, which regulated GhICS1 expression to determine salicylic acid level. Our data documented that numerous later-inducible miRNAs in the plant response to V. dahliae, suggesting that these miRNAs play important roles in plant resistance to vascular disease.

Spatially Resolved Localization of Lanthanum and Cerium in the Rare Earth Element Hyperaccumulator Fern Dicranopteris linearis from China.

The fern Dicranopteris linearis (Gleicheniaceae) from China is a hyperaccumulator of rare earth element (REE), but little is known about the ecophysiology of REE in this species. This study aimed to clarify tissue-level and organ-level distribution of REEs via synchrotron-based X-ray fluorescence microscopy (XFM). The results show that REEs (La + Ce) are mainly colocalized with Mn in the pinnae and pinnules, with the highest concentrations in necrotic lesions and lower concentrations in veins. In the cross sections of the pinnules, midveins, rachis, and stolons, La + Ce and Mn are enriched in the epidermis, vascular bundles, and pericycle (midvein). In these tissues, Mn is localized mainly in the cortex and mesophyll. We hypothesize that the movement of REEs in the transpiration flow in the veins is initially restricted in the veins by the pericycle between vascular bundle and cortex, while excess REEs are transported by evaporation and cocompartmentalized with Mn in the necrotic lesions and epidermis in an immobile form, possibly a Si-coprecipitate. The results presented here provide insights on how D. linearis regulates high concentrations of REEs in vivo, and this knowledge is useful for developing phytotechnological applications (such as REE agromining) using this fern in REE-contaminated sites in China.