Sampling Conformational Ensembles of Highly Dynamic Proteins via Generative Deep Learning.

Proteins are inherently dynamic, and their conformational ensembles are functionally important in biology. Large-scale motions may govern protein structure-function relationship, and numerous transient but stable conformations of intrinsically disordered proteins (IDPs) can play a crucial role in biological function. Investigating conformational ensembles to understand regulations and disease-related aggregations of IDPs is challenging both experimentally and computationally. In this paper first an unsupervised deep learning-based model, termed Internal Coordinate Net (ICoN), is developed that learns the physical principles of conformational changes from molecular dynamics (MD) simulation data. Second, interpolating data points in the learned latent space are selected that rapidly identify novel synthetic conformations with sophisticated and large-scale sidechains and backbone arrangements. Third, with the highly dynamic amyloid-ß1-42 (Aß42) monomer, our deep learning model provided a comprehensive sampling of Aß42's conformational landscape. Analysis of these synthetic conformations revealed conformational clusters that can be used to rationalize experimental findings. Additionally, the method can identify novel conformations with important interactions in atomistic details that are not included in the training data. New synthetic conformations showed distinct sidechain rearrangements that are probed by our EPR and amino acid substitution studies. The proposed approach is highly transferable and can be used for any available data for training. The work also demonstrated the ability for deep learning to utilize learned natural atomistic motions in protein conformation sampling.

Sampling Conformational Ensembles of Highly Dynamic Proteins via Generative Deep Learning.

Proteins are inherently dynamic, and their conformational ensembles are functionally important in biology. Large-scale motions may govern protein structure-function relationship, and numerous transient but stable conformations of intrinsically disordered proteins (IDPs) can play a crucial role in biological function. Investigating conformational ensembles to understand regulations and disease-related aggregations of IDPs is challenging both experimentally and computationally. In this paper we first introduced an unsupervised deep learning-based model, termed Internal Coordinate Net (ICoN), which learns the physical principles of conformational changes from molecular dynamics (MD) simulation data. Second, we selected interpolating data points in the learned latent space that rapidly identify novel synthetic conformations with sophisticated and large-scale sidechains and backbone arrangements. Third, with the highly dynamic amyloid-ß 1-42 (Aß42) monomer, our deep learning model provided a comprehensive sampling of Aß42's conformational landscape. Analysis of these synthetic conformations revealed conformational clusters that can be used to rationalize experimental findings. Additionally, the method can identify novel conformations with important interactions in atomistic details that are not included in the training data. New synthetic conformations showed distinct sidechain rearrangements that are probed by our EPR and amino acid substitution studies. This approach is highly transferable and can be used for any available data for training. The work also demonstrated the ability for deep learning to utilize learned natural atomistic motions in protein conformation sampling.

Rejuvenation of peripheral immune cells attenuates Alzheimer's disease-like pathologies and behavioral deficits in a mouse model.

Immunosenescence contributes to systematic aging and plays a role in the pathogenesis of Alzheimer's disease (AD). Therefore, the objective of this study was to investigate the potential of immune rejuvenation as a therapeutic strategy for AD. To achieve this, the immune systems of aged APP/PS1 mice were rejuvenated through young bone marrow transplantation (BMT). Single-cell RNA sequencing revealed that young BMT restored the expression of aging- and AD-related genes in multiple cell types within blood immune cells. The level of circulating senescence-associated secretory phenotype proteins was decreased following young BMT. Notably, young BMT resulted in a significant reduction in cerebral Aß plaque burden, neuronal degeneration, neuroinflammation, and improvement of behavioral deficits in aged APP/PS1 mice. The ameliorated cerebral amyloidosis was associated with an enhanced Aß clearance of peripheral monocytes. In conclusion, our study provides evidence that immune system rejuvenation represents a promising therapeutic approach for AD.

A meta-analysis comparing phenol treatment with surgical excision for pilonidal sinus.

Pilonidal sinus is a chronic condition characterized by inflammation, swelling, and pain in the sacrococcygeal region. In recent years, the rate of recurrence and wound complications in PSD remains high, and no treatment is universally accepted. This study aimed to compare the efficacy of phenol treatment with surgical excision treatment for PSD through a meta-analysis of controlled clinical trials. We searched three electronic databases, PubMed, Embase, and Cochrane library, to comprehensively search the literature comparing phenol treatment and surgical treatment of pilonidal sinus. Fourteen publications were included, including five RCTs and nine non-RCTs. The phenol group had a slightly higher rate of disease recurrence than the surgical group (RR = 1.12, 95% CI [0.77,1.63]), but the difference was not statistically significant (P = 0.55 > 0.05). As compared to the surgical group, wound complications were considerably less common (RR = 0.40, 95% CI [0.27,0.59]). Phenol treatment resulted in a significantly shorter operating time than surgery treatment (weighted mean difference -22.76, 95% CI [-31.13,-14.39]). The time to return to daily work was considerably shorter than in the surgical group (weighted mean difference -10.11, 95% CI [-14.58,-5.65]). Postoperative complete healing time was significantly shorter than surgical healing time (weighted mean difference -17.11, 95% CI [-32.18,-2.03]). Phenol treatment is effective for pilonidal sinus disease, and its recurrence rate is not significantly different from surgical treatment. The greatest advantage of phenol treatment is the low incidence of wound complications. Moreover, the time required for treatment and recovery are significantly lower than for surgical treatment.

A spatiotemporal barrier formed by Follistatin is required for left-right patterning.

How left-right (LR) asymmetry emerges in a patterning field along the anterior-posterior axis remains an unresolved problem in developmental biology. Left-biased Nodal emanating from the LR organizer propagates from posterior to anterior (PA) and establishes the LR pattern of the whole embryo. However, little is known about the regulatory mechanism of the PA spread of Nodal and its asymmetric activation in the forebrain. Here, we identify bilaterally expressed Follistatin (Fst) as a regulator blocking the propagation of the zebrafish Nodal ortholog Southpaw (Spaw) in the right lateral plate mesoderm (LPM), and restricting Spaw transmission in the left LPM to facilitate the establishment of a robust LR asymmetric Nodal patterning. In addition, Fst inhibits the Activin-Nodal signaling pathway in the forebrain thus preventing Nodal activation prior to the arrival, at a later time, of Spaw emanating from the left LPM. This contributes to the orderly propagation of asymmetric Nodal activation along the PA axis. The LR regulation function of Fst is further confirmed in chick and frog embryos. Overall, our results suggest that a robust LR patterning emerges by counteracting a Fst barrier formed along the PA axis.

Physiological ß-amyloid clearance by the liver and its therapeutic potential for Alzheimer's disease.

Cerebral amyloid-ß (Aß) accumulation due to impaired Aß clearance is a pivotal event in the pathogenesis of Alzheimer's disease (AD). Considerable brain-derived Aß is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery. Whether the liver physiologically clears circulating Aß and its therapeutic potential for AD remains unclear. Here, we found that about 13.9% of Aß42 and 8.9% of Aß40 were removed from the blood when flowing through the liver, and this capacity was decreased with Aß receptor LRP-1 expression down-regulated in hepatocytes in the aged animals. Partial blockage of hepatic blood flow increased Aß levels in both blood and brain interstitial fluid. The chronic decline in hepatic Aß clearance via LRP-1 knockdown specific in hepatocytes aggravated cerebral Aß burden and cognitive deficits, while enhancing hepatic Aß clearance via LRP-1 overexpression attenuated cerebral Aß deposition and cognitive impairments in APP/PS1 mice. Our findings demonstrate that the liver physiologically clears blood Aß and regulates brain Aß levels, suggesting that a decline of hepatic Aß clearance during aging could be involved in AD development, and hepatic Aß clearance is a novel therapeutic approach for AD.

Superb Microvascular Imaging for the Differentiation of Benign and Malignant Breast Lesions: A System Review and Meta-Analysis.

OBJECTIVE: To evaluate the diagnostic performance of SMI in the diagnosis of benign and malignant breast lesions. METHODS: A systematic search of PubMed, EMBASE, Cochrane, OVID, SCI, and SCOPUS was performed to find relevant studies which applied SMI to differentiate benign and malignant breast lesions. All the studies were published before October 10, 2022. Only studies published in English were collected. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was applied to assess the quality of the included studies. Summary receiver operating characteristic (SROC) modeling was also performed to the diagnostic performance of SMI in the diagnosis of benign and malignant breast lesions. Subgroup analyses and meta-regression were performed to find out the heterogeneity. RESULTS: Twenty studies which include a total of 2873 lesions (1748 benign and 1125 malignant) in 2740 patients were evaluated in this meta-analysis. The summary sensitivity and specificity were 0.82 (95% confidence interval [CI]: 0.76-0.86), 0.70 (95% CI: 0.64-0.76) for SMI vascular degree, 0.77 (95% CI: 0.67-0.84), 0.79 (95% CI: 0.75-0.83) for SMI vascular distribution, 0.78 (95% CI: 0.70-0.84), 0.75 (95% CI: 0.69-0.80) for SMI vascular morphology, 0.81 (95% CI: 0.72-0.87), 0.80 (95% CI: 0.75-0.85) SMI penetration vessel. For SMI overall vascular features, the summary sensitivity and summary specificity were 0.74 (95% CI: 0.61-0.84) and 0.80 (95% CI: 0.76-0.84). The result of subgroup analysis and meta-analysis showed malignant rate and country might be the cause of heterogeneity of diagnostic accuracy of vascular grade and morphology. CONCLUSION: SMI vascular features have high sensitivity and specificity in the differentiation of benign and malignant lesions. Future international multicenter studies in various regions with large sample size are required to confirm these findings.

Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease.

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aß neurotoxicity and promotes Aß clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.

Binding Kinetics Toolkit for Analyzing Transient Molecular Conformations and Computing Free Energy Landscapes.

Understanding ligand binding kinetics and thermodynamics, which involves investigating the free, transient, and final complex conformations, is important in fundamental studies and applications for chemical and biomedical systems. Examining the important but transient ligand-protein-bound conformations, in addition to experimentally determined structures, also provides a more accurate estimation for drug efficacy and selectivity. Moreover, obtaining the entire picture of the free energy landscape during ligand binding/unbinding processes is critical in understanding binding mechanisms. Here, we present a Binding Kinetics Toolkit (BKiT) that includes several utilities to analyze trajectories and compute a free energy and kinetics profile. BKiT uses principal component space to generate approximated unbinding or conformational transition coordinates for accurately describing and easily visualizing the molecular motions. We implemented a new partitioning approach to assign indexes along the approximated coordinates that can be used as milestones or microstates. The program can generate input files to run many short classical molecular dynamics simulations and uses milestoning theory to construct the free energy profile and estimate binding residence time. We first validated the method with a host-guest system, aspirin unbinding from ß-cyclodextrin, and then applied the protocol to pyrazolourea compounds and cyclin-dependent kinase 8 and cyclin C complexes, a kinase system of pharmacological interest. Overall, our approaches yielded good agreement with published results and suggest ligand design strategies. The computed unbinding free energy landscape also provides a more complete picture of ligand-receptor binding barriers and stable local minima for deepening our understanding of molecular recognition. BKiT is easy to use and has extensible features for future expansion of utilities for postanalysis and calculations.

Polysaccharide Krestin Prevents Alzheimer's Disease-type Pathology and Cognitive Deficits by Enhancing Monocyte Amyloid-ß Processing.

Deficits in the clearance of amyloid ß protein (Aß) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer's disease (AD). Impaired uptake of Aß by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aß clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Aß uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Aß deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aß clearance by blood monocytes and alleviating AD-like pathology.

Harnessing Shape Complementarity for Upgraded Cyclohexane Purification through Adaptive Bottlenecked Pores in an Imidazole-Containing MOF.

Shape complementarity is a biological craft for precisely binding substrates at protein-protein interfaces. An analogy to such a function can be drawn conceptually for crystalline porous solids; yet the manifested entities are rare in reticular chemistry. The bottleneck-shaped pores carved out of a metal-organic framework, Zn(MIBA)2 (aka. MAF-stu-13), can perfectly accommodate benzene molecules. Remarkably, its framework adapts to the optimal guest binding-the enhanced host-guest interactions in the neck in turn minimize the guest-guest repulsion in the pore to the extent it turns into attraction-as demonstrated by the combined X-ray structural and DFT computational studies. This adaptive material can be used for liquid-phase production of ultrahigh-purity (≥99 %) cyclohexane, achieving a balance between uptake capacity and separation selectivity and surpassing the performances of other porous and nonporous crystals reported recently (e.g. product purity 99.4 % vs. 97.5 % to date).

The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D.

The initiation of cell division integrates a large number of intra- and extracellular inputs. D-type cyclins (hereafter, cyclin D) couple these inputs to the initiation of DNA replication1. Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. Accordingly, increased levels and activity of cyclin D-CDK4/6 complexes are strongly linked to unchecked cell proliferation and cancer2,3. However, the mechanisms that regulate levels of cyclin D are incompletely understood4,5. Here we show that autophagy and beclin 1 regulator 1 (AMBRA1) is the main regulator of the degradation of cyclin D. We identified AMBRA1 in a genome-wide screen to investigate the genetic basis of  the response to CDK4/6 inhibition. Loss of AMBRA1 results in high levels of cyclin D in cells and in mice, which promotes proliferation and decreases sensitivity to CDK4/6 inhibition. Mechanistically, AMBRA1 mediates ubiquitylation and proteasomal degradation of cyclin D as a substrate receptor for the cullin 4 E3 ligase complex. Loss of AMBRA1 enhances the growth of lung adenocarcinoma in a mouse model, and low levels of AMBRA1 correlate with worse survival in patients with lung adenocarcinoma. Thus, AMBRA1 regulates cellular levels of cyclin D, and contributes to cancer development and the response of cancer cells to CDK4/6 inhibitors.

Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer's disease.

Amyloid-ß (Aß) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aß produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aß clearance remain largely unknown. The kidney is thought to be responsible for Aß clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aß in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aß clearance via the kidney were assessed. We detected Aß in the kidneys and urine of both humans and animals and found that the Aß level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aß deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aß levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aß from the blood, suggesting that facilitation of Aß clearance via the kidney represents a novel potential therapeutic approach for AD.

Ubiquitination in the regulation of inflammatory cell death and cancer.

The ubiquitin system is complex, multifaceted, and is crucial for the modulation of a vast number of cellular processes. Ubiquitination is tightly regulated at different levels by a range of enzymes including E1s, E2s, and E3s, and an array of DUBs. The UPS directs protein degradation through the proteasome, and regulates a wide array of cellular processes including transcription and epigenetic factors as well as key oncoproteins. Ubiquitination is key to the dynamic regulation of programmed cell death. Notably, the TNF signaling pathway is controlled by competing ubiquitin conjugation and deubiquitination, which governs both proteasomal degradation and signaling complex formation. In the inflammatory response, ubiquitination is capable of both activating and dampening inflammasome activation through the control of either protein stability, complex formation, or, in some cases, directly affecting receptor activity. In this review, we discuss the enzymes and targets in the ubiquitin system that regulate fundamental cellular processes regulating cell death, and inflammation, as well as disease consequences resulting from their dysregulation. Finally, we highlight several pre-clinical and clinical compounds that regulate ubiquitin system enzymes, with the aim of restoring homeostasis and ameliorating diseases.

Blood cell-produced amyloid-ß induces cerebral Alzheimer-type pathologies and behavioral deficits.

It is traditionally believed that cerebral amyloid-beta (Aß) deposits are derived from the brain itself in Alzheimer's disease (AD). Peripheral cells such as blood cells also produce Aß. The role of peripherally produced Aß in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced Aß to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human Aß in the blood, and caused AD phenotypes including Aß plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood Aß levels, and alleviated brain Aß burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced Aß plays a significant role in AD pathogenesis, and the elimination of peripheral production of Aß can decrease brain Aß deposition and represents a novel therapeutic approach for AD.

Amyloid-beta uptake by blood monocytes is reduced with ageing and Alzheimer's disease.

Deficits in the clearance of amyloid ß-protein (Aß) play a pivotal role in the pathogenesis of sporadic Alzheimer's disease (AD). The roles of blood monocytes in the development of AD remain unclear. In this study, we sought to investigate the alterations in the Aß phagocytosis function of peripheral monocytes during ageing and in AD patients. A total of 104 cognitively normal participants aged 22-89 years, 24 AD patients, 25 age- and sex-matched cognitively normal (CN) subjects, 15 Parkinson's disease patients (PD), and 15 age- and sex-matched CN subjects were recruited. The Aß uptake by blood monocytes was measured and its alteration during ageing and in AD patients were investigated. Aß1-42 uptake by monocytes decreased during ageing and further decreased in AD but not in PD patients. Aß1-42 uptake by monocytes was associated with Aß1-42 levels in the blood. Among the Aß uptake-related receptors and enzymes, the expression of Toll-like receptor 2 (TLR2) was reduced in monocytes from AD patients. Our findings suggest that monocytes regulate the blood levels of Aß and might be involved in the development of AD. The recovery of the Aß uptake function by blood monocytes represents a potential therapeutic strategy for AD.

[Research progress of liver injury induced by Polygoni Mulitiflori Radix].

Polygoni Mulitiflori Radix, or dried root tuber of Polygonum multiflorum(PM), is a traditional Chinese tonic medicine, with the effect in nourishing liver and kidney, and benefiting blood essence and hair. It is widely used in clinical and healthcare products. In recent years, more and more reports about adverse reactions of root tuber of P.multiflorum and its preparations have been reported. Fortunately, there is also substantial progress in the experimental study on liver injury induced by PM. According to the literature review, the possible causes of liver injury were found to be the mixture of raw and processed PM and long-term high-dose administration. In addition, the liver injury induced by PM is idiosyncratic liver injury, and individual factors are also the important cause. At the same time, according to the literature reports, the effects of chemical components in different pathological animal models were summarized, finding that 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside was the main component for liver injury; based on the clinical manifestations of liver injury induced by PM, the effects of some chemical components on bilirubin and bile acid metabolism were analyzed. This paper reviews the study progress of liver injury induced by PM.

Transient States and Barriers from Molecular Simulations and the Milestoning Theory: Kinetics in Ligand-Protein Recognition and Compound Design.

This study presents a novel computational approach to study molecular recognition and binding kinetics for drug-like compounds dissociating from a flexible protein system. The intermediates and their free energy profile during ligand association and dissociation processes control ligand-protein binding kinetics and bring a more complete picture of ligand-protein binding. The method applied the milestoning theory to extract kinetics and thermodynamics information from running short classical molecular dynamics (MD) simulations for frames from a given dissociation path. High-dimensional ligand-protein motions (3N-6 degrees of freedom) during ligand dissociation were reduced by use of principal component modes for assigning more than 100 milestones, and classical MD runs were allowed to travel multiple milestones to efficiently obtain ensemble distribution of initial structures for MD simulations and estimate the transition time and rate during ligand traveling between milestones. We used five pyrazolourea ligands and cyclin-dependent kinase 8 with cyclin C (CDK8/CycC) as our model system as well as metadynamics and a pathway search method to sample dissociation pathways. With our strategy, we constructed the free energy profile for highly mobile biomolecular systems. The computed binding free energy and residence time correctly ranked the pyrazolourea ligand series, in agreement with experimental data. Guided by a barrier of a ligand passing an αC helix and activation loop, we introduced one hydroxyl group to parent compounds to design our ligands with increased residence time and validated our prediction by experiments. This work provides a novel and robust approach to investigate dissociation kinetics of large and flexible systems for understanding unbinding mechanisms and designing new small-molecule drugs with desired binding kinetics.

Antioxidant and Compositional HPLC Analysis of Three Common Bamboo Leaves.

Bamboo leaves of Phyllostachys nigra (PN), Lophatherum gracile (LG), and Pleioblastus amarus (PA) are three common herbs in China. In this work, a new high performance liquid chromatography (HPLC) method for the simultaneous determination of seven compounds in bamboo leaves has been developed; and PN, LG, and PA leaves were analyzed. PN showed four times as much chlorogenic acid (CA) than the other two, and contained the most isoorientin (iso-ORI) and isovitexin (iso-VIT) as well. The PA presented the most orientin (ORI) and LG covered a majority of cynaroside (CYN). We measured the antioxidant activity by scavenging the stable 2,2-diphenyl-1-pyridinohydrazinyl (DPPH) free radicals, and found that Luteolin (inhibitory concentration (IC)50 = 0.42 µM, LUT) and CYN (IC50 = 0.43 µM) showed 2-3 times higher antioxidant activity than iso-ORI (IC50 = 0.81 µM), ORI (IC50 = 0.84 µM), and other related antioxidant standards such as trolox (IC50 = 0.97 µM) and ascorbic acid (IC50 = 0.93 µM, VC). Among extracts, PN and PA showed considerable antioxidant activity, which was related well with the contents of CA, iso-ORI, and iso-VIT (p < 0.05). This study firstly provides evidence for functional antioxidant compounds of bamboo leaves based on statistical analysis of the HPLC analysis and DPPH assay, and it lays a foundation for its further development or utilization.

Sensitive and selective assay of uranyl based on the aggregation induced fluorescent quenching of protamine capped gold nanoclusters.

The protamine capped gold nanoclusters (AuNCs@PRT) were synthesized by an one-pot approach, and utilized as a nanoprobe for highly sensitive and selective assay of U(VI) ions. The method is based on the aggregation induced fluorescent quenching of AuNCs@PRT by U(VI) ions. Under optimum conditions, the decrease of fluorescence intensity displayed a good linear correlation with the concentration of U(VI) ions ranging from 20.4 nM to 9.74 µM, with a detection limit of 6.1 nM. The relative standard deviations were 3.86%, 1.41% and 1.71% via 11 detections at concentrations of 40 nM, 0.40 µM and 4.0 µM of U(VI), respectively. The quenching mechanism was demonstrated to be due to the binding of U(VI) towards PRT to cause the aggregation of AuNCs@PRT rather than metal-metal interaction. The results suggest the potential application of this approach for monitoring the level of U(VI) in environmental samples.