Chiral assemblies of pinwheel superlattices on substrates.

The unique topology and physics of chiral superlattices make their self-assembly from nanoparticles highly sought after yet challenging in regard to (meta)materials1-3. Here we show that tetrahedral gold nanoparticles can transform from a perovskite-like, low-density phase with corner-to-corner connections into pinwheel assemblies with corner-to-edge connections and denser packing. Whereas corner-sharing assemblies are achiral, pinwheel superlattices become strongly mirror asymmetric on solid substrates as demonstrated by chirality measures. Liquid-phase transmission electron microscopy and computational models show that van der Waals and electrostatic interactions between nanoparticles control thermodynamic equilibrium. Variable corner-to-edge connections among tetrahedra enable fine-tuning of chirality. The domains of the bilayer superlattices show strong chiroptical activity as identified by photon-induced near-field electron microscopy and finite-difference time-domain simulations. The simplicity and versatility of substrate-supported chiral superlattices facilitate the manufacture of metastructured coatings with unusual optical, mechanical and electronic characteristics.

Electron Microscopy Studies of Soft Nanomaterials.

This review highlights recent efforts on applying electron microscopy (EM) to soft (including biological) nanomaterials. We will show how developments of both the hardware and software of EM have enabled new insights into the formation, assembly, and functioning (e.g., energy conversion and storage, phonon/photon modulation) of these materials by providing shape, size, phase, structural, and chemical information at the nanometer or higher spatial resolution. Specifically, we first discuss standard real-space two-dimensional imaging and analytical techniques which are offered conveniently by microscopes without special holders or advanced beam technology. The discussion is then extended to recent advancements, including visualizing three-dimensional morphology of soft nanomaterials using electron tomography and its variations, identifying local structure and strain by electron diffraction, and recording motions and transformation by in situ EM. On these advancements, we cover state-of-the-art technologies designed for overcoming the technical barriers for EM to characterize soft materials as well as representative application examples. The even more recent integration of machine learning and its impacts on EM are also discussed in detail. With our perspectives of future opportunities offered at the end, we expect this review to inspire and stimulate more efforts in developing and utilizing EM-based characterization methods for soft nanomaterials at the atomic to nanometer length scales in academic research and industrial applications.

Formation and impact of nanoscopic oriented phase domains in electrochemical crystalline electrodes.

Electrochemical phase transformation in ion-insertion crystalline electrodes is accompanied by compositional and structural changes, including the microstructural development of oriented phase domains. Previous studies have identified prevailingly transformation heterogeneities associated with diffusion- or reaction-limited mechanisms. In comparison, transformation-induced domains and their microstructure resulting from the loss of symmetry elements remain unexplored, despite their general importance in alloys and ceramics. Here, we map the formation of oriented phase domains and the development of strain gradient quantitatively during the electrochemical ion-insertion process. A collocated four-dimensional scanning transmission electron microscopy and electron energy loss spectroscopy approach, coupled with data mining, enables the study. Results show that in our model system of cubic spinel MnO2 nanoparticles their phase transformation upon Mg2+ insertion leads to the formation of domains of similar chemical identity but different orientations at nanometre length scale, following the nucleation, growth and coalescence process. Electrolytes have a substantial impact on the transformation microstructure ('island' versus 'archipelago'). Further, large strain gradients build up from the development of phase domains across their boundaries with high impact on the chemical diffusion coefficient by a factor of ten or more. Our findings thus provide critical insights into the microstructure formation mechanism and its impact on the ion-insertion process, suggesting new rules of transformation structure control for energy storage materials.

Insight into the status of plasma renin and aldosterone measurement: findings from 526 clinical laboratories in China.

OBJECTIVES: Accurate measurements of renin and aldosterone levels play an important role in primary aldosteronism screening, which is of great importance in the management and categorization of hypertension. The objective of this study is to investigate the current status of plasma renin and aldosterone measurements in China, which is achieved by analyzing the results of 526 clinical laboratories nationwide for three pooled fresh plasma samples derived from more than 2,000 patients. METHODS: Renin and aldosterone in three pooled plasma samples were measured four times in 526 laboratories employing various measurement systems. The inter- and intra-laboratory %CV were calculated and compared. To determine the source of the substantial inter-laboratory %CV, laboratories were categorized according to the measurement systems they are using, and both the inter- and intra-measurement-system %CV were calculated and compared. RESULTS: Regarding renin, the majority of laboratories use four primary commercial immunoassays. However, for aldosterone, in addition to commercial immunoassays, laboratory-developed liquid chromatography-tandem mass spectrometry (LC-MS) methods are also used by laboratories. The median values of intra-laboratory %CVs, intra-measurement-system %CVs, inter-laboratory %CVs, and inter-measurement systems %CVs varied between 1.6 and 2.6 %, 4.6 and 14.9 %, 8.3 and 25.7 %, and 10.0 and 34.4 % for renin, respectively. For aldosterone, these values ranged from 1.4 to 2.2 %, 2.5-14.7 %, 9.9-31.0 %, and 10.0-35.5 %, respectively. CONCLUSIONS: The precision within laboratories and measurement systems for plasma renin and aldosterone measurements is satisfactory. However, the comparability between laboratories using different measurement systems remains lacking, indicating the long way to achieve standardization and harmonization for these two analytes.

Choline and trimethylamine N-oxide supplementation in normal chow diet and western diet promotes the development of atherosclerosis in Apoe -/- mice through different mechanisms.

Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, has been shown to aggravate cardiovascular disease. However, the mechanisms of TMAO in the setting of cardiovascular disease progress remain unclear. Here, we aim to investigate the effects of TMAO on atherosclerosis (AS) development and the underlying mechanisms. Apoe -/- mice received choline or TMAO supplementation in a normal diet and a western diet for 12 weeks. Choline or TMAO supplementation in both normal diet and western diet significantly promoted plaque progression in Apoe-/- mice. Besides, serum lipids levels and inflammation response in the aortic root were enhanced by choline or TMAO supplementation. In particular, choline or TMAO supplementation in the western diet changed intestinal microbiota composition and bile acid metabolism. Therefore, choline or TMAO supplementation may promote AS by modulating gut microbiota in mice fed with a western diet and by other mechanisms in mice given a normal diet, even choline or TMAO supplementation in a normal diet can promote AS.

Performance of HDL-C measurements assessed by a 4-year trueness-based EQA/PT program in China.

OBJECTIVES: A trueness-based EQA/PT program for high density lipoprotein cholesterol (HDL-C) was initiated. We analyzed the 4 year EQA/PT program to overview the measurement standardization for HDL-C in China. METHODS: Two levels of freshly frozen, commutable serum external quality assessment/proficiency testing (EQA/PT) materials were prepared and determined by reference measurement procedure each year. The samples were delivered to clinical laboratories and measured 15 times in 3 days. The precision [coefficient of variation (CV)], trueness (bias), and accuracy [total error (TE)] were calculated and used to evaluate measurement performance. The pass rates of individual laboratories and peer groups were analyzed using the acceptable performance from the National Cholesterol Education Program (NCEP) and biological variation as the evaluation criteria. RESULTS: More than 60% of laboratories use heterogeneous systems, and there was a decrease in the percentage from 2016 to 2019. About 95, 78, and 33% of laboratories met the minimum, desirable and optimum TE criteria derived from biological variation. The pass rates were 87.0% (84.7-88.8%), 58.7% (55.3-62.4%), and 97.3% (95.6-98.3%) that met the acceptable performance of TE, bias, and CV of NCEP. The homogeneous systems had higher pass rates of TE, bias, and CV than the heterogeneous groups in 2016, but they did not show apparent advantages in 2017-2019. CONCLUSIONS: The trueness-based EQA/PT program can be used to evaluate the accuracy, reproducibility, and trueness of results. For some IVD manufacturers and individual laboratories, accuracy, especially trueness, are still problems. Efforts should be made to improve the situation and achieve better HDL-C measurement standardization.

Age and sex specific reference intervals of 13 hematological analytes in Chinese children and adolescents aged from 28 days up to 20 years: the PRINCE study.

OBJECTIVES: Pediatric Reference Intervals in China (PRINCE) is a nationwide initiative that aims to establish and validate harmonized reference intervals (RIs) for Chinese children and adolescents, in which 15,150 healthy volunteers aged up to 20 years were recruited from 11 centers to establish RIs and 7,557 children and adolescents were enrolled from 21 centers to validate RIs. METHODS: The complete blood cell counts (CBC) of venous whole blood were measured by hematology analyzers through Sysmex systems in different centers. Age- and sex-specific RIs were calculated according to the guidelines. RESULTS: Unlike adults with certain levels of analyte concentrations, hematological parameters of children changed through growth and development. Red blood cell counts, hemoglobin, and hematocrit increased with age, and revealed higher concentrations in boys than girls after puberty. White blood cell counts and platelet counts showed significant higher levels than adults before 2 years of age, and then gradually decreased without distinct sex differences. In addition, lymphocyte counts decreased with age while neutrophil counts showed an opposite trend. The lower and upper limits of pediatric RIs of CBC were different from those of adults. CONCLUSIONS: The validation of RIs indicated that the PRINCE study provided a version of RIs suitable for most of regions in China. This first harmonized pediatric RIs of CBC across China provided a robust database to understand the dynamic changes of hematologic parameters from birth to adolescence, and will contribute to clinical diagnosis and prognosis evaluation for pediatric patients as well.

Reference intervals of 14 biochemical markers for children and adolescence in China: the PRINCE study.

OBJECTIVES: The Pediatric Reference Intervals in China (PRINCE) was initiated to establish the reference intervals (RIs) of Chinese children, as well as to make it possible to compare the variability of biochemical markers among countries internationally. METHODS: Healthy participants, aged up to 20 years, from 11 provinces across China, were enrolled in PRINCE and according to a standard screening procedure, that included a questionnaire survey, physical examinations and laboratory tests. Fasting venous blood specimens were collected. All serum specimens were analyzed with Cobas C702 in the center laboratory, i.e. clinical laboratory of Beijing Children's Hospital, with certified qualification (ISO15189). The nonparametric method recommended by Clinical Laboratory Standards Institute guidelines, was used to calculate the age- and sex-specified RIs. RESULTS: Among the 15,150 participants enrolled, 12,352 children (6,093 males and 6,259 females) were included to calculate RIs. The RIs for total protein, albumin, globulin, calcium, phosphate, potassium, sodium, chlorine, alkaline phosphatase, γ-glutamyl transpeptadase, alanine aminotransferase, aspartate aminotransferase, creatinine and urea were established by age- or sex-partitions. Most biochemical markers displayed larger variability and higher dispersion during the periods between 28 days and 1 year old, and included 4-6 age partitions commonly during 1 to <20 years old. In addition, differences of RIs between sexes usually occurs around the initiation of puberty at 12-13 years old. CONCLUSIONS: The age- and sex-specified RIs of 14 biochemical markers in PRINCE study can provide a solid reference, which will be transferred into relevant RIs for other clinical laboratory's platforms according to the CLSI guidelines.

lncRNAs MALAT1 and LINC00657 upstream to miR-214-3p/BMP2 regulate osteogenic differentiation of human mesenchymal stem cells.

BACKGROUND: Osteogenic differentiation of human mesenchymal stem cells (hMSCs) holds significant clinical implications for patients with bone diseases. LncRNAs are an emerging group of epigenetic modulators involved in the osteogenesis of hMSCs. In this study, we explored lncRNA profiles that are upstream to the hsa-miR-214-3p/BMP2 axis in osteogenic differentiation of hMSCs. METHOD: HMSCs were induced toward osteogenesis for 14 days. Between day 1 and day 14, qRT-PCR was conducted to compare the expressions of BMP2, Runx2, hsa-miR-214-3p, and biochemical assays to compare alkaline phosphatase and Alizarin Red S activities. 145 lncRNAs, which were experimentally confirmed upstream to hsa-miR-214-3p were examined. Five significantly upregulated lncRNAs, MEG3, SNHG16, FAM83H-AS1, MALAT1 and LINC00657 were downregulated in differentiated hMSCs and their impact on osteogenic differentiation were examined. Hsa-miR-214-3p was silenced in lncRNAs-downregulated hMSCs to further examine the association between lncRNAs and hsa-miR-214-3p/BMP2 axis. RESULTS: From day 1 to day 14, hMSCs underwent significant osteogenic differentiation, and KCNQ1OT1, MEG3, SNHG16, FAM83H-AS1, MALAT1 and LINC00657 were significantly upregulated. Downregulations of MEG3, SNHG16, FAM83H-AS1, MALAT1 and LINC00657 all suppressed osteogenic differentiation. However, qRT-PCR and RIP assay demonstrated that only MALAT1 and LINC00657 acted through hsa-miR-214-3p/BMP2 to regulate osteogenic differentiation. Furthermore, silencing hsa-miR-214-3p only rescued osteogenic differentiation in MALAT1- or LINC00657- downregulated hMSCs. CONCLUSIONS: Our data strongly indicated that lncRNAs MALAT1 and LINC00657 acted through miR-214-3p/BMP2 axis to regulate osteogenic differentiation of hMSCs.

Serum glutamate and glutamine-to-glutamate ratio are associated with coronary angiography defined coronary artery disease.

BACKGROUND AND AIMS: Serum concentrations of glutamate (Glu), Glutamine (Gln) and Gln/Glu ratio have consistently been reported to be associated with metabolic disorders and diabetes. The aim of this study was to examine the relationship between these metabolites with the presence of coronary artery disease (CAD) and CAD severity in Chinese patients. METHODS AND RESULTS: 2970 Chinese patients undergoing coronary angiography (CAG) in Beijing Hospital were enrolled. Baseline demographics and medical history data was recorded by questionnaires. Serum Glu and Gln concentrations were analyzed by isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). Statistical analysis showed that CAD patients had significantly higher levels of Glu and lower Gln/Glu ratios compared with non-CAD control group. Glu was significantly positively associated with body mass index (BMI), fasting blood glucose (FBG), triglycerides (TG), creatinine (Crea), and uric acid (UA), and negatively associated with high-density lipoprotein cholesterol (HDL-C), while inverse associations between Gln/Glu ratio and these risk factors were observed. Glu levels increased and Gln/Glu decreased with the increase of CAD severity as represented by either the number of stenosed vessels or the Gensini scores. Logistic regression analysis demonstrated that, after adjusting for smoking status, obesity or overweight, hypertension, dyslipidemia, diabetes, stroke and family history of premature CAD, high Glu level and low Gln/Glu ratio were positively associated with CAG defined CAD as well as CAD severity expressed by Gensini score. CONCLUSIONS: We identified Glu and Gln/Glu ratio independently associated with CAG defined CAD as well as CAD severity in Chinese patients undergoing CAG.

The consistency of aminotransferase analysis in China: a comparison of six mainstream aminotransferase routine methods and recalibration using human pooled serum preparations supplemented with human recombinant aminotransferases.

Background: To evaluate the consistency of six mainstream homogeneous systems for aminotransferase measurements and improve the consistency of measurements by applying uniform calibrators.Methods: 200 individual samples were grouped into four sets for assays with and without pyridoxal-5-phosphate (P-5'-P) for Alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Routine assays for the P-5'-P group were compared with a reference measurement procedure (RMP). In the non-P-5'-P group, four routine assays were analyzed in a pairwise method across six method pairs. Recalibration was performed using human serum pools (HSPs) supplemented with human original recombinant aminotransferases (HOR). Data were analyzed by Passing-Bablok regression and Bland-Altman plots.Results: In the P-5'-P group, the mean biases for Ortho and Dimension assays for ALT were 17.0% and -25.4%, respectively; for AST, the mean biases were -9.5% and -9.6%, respectively. In the non-P-5'-P group, the mean deviations ranged from -5.9% to 5.9% for ALT. For AST, the relative deviations ranged from -19.1% to 6.5%. After recalibration, in the P-5'-P group, the relative biases were reduced to -12.2% to 7.7% for ALT and -6.9% to 0.8% for AST. The mean deviations for the non-P-5'-P AST group were reduced remarkably (-3.0% to 3.3%).Conclusion: Assays supplemented with P-5'-P exhibited poor performance against RMP for both ALT and AST. For assays without P-5'-P, AST results showed non-satisfactory comparability for almost all method pairs. Uniform calibrators such as HSPs supplemented with HOR could improve consistency among the mainstream homogeneous systems for the measurement of aminotransferase activity, particularly for AST measurement.

A candidate reference method and multiple commutable control materials for serum 25-hydroxyvitamin D measurement.

OBJECTIVES: The aim of the current study was to establish a reliable candidate reference method for serum 25-hydroxyvitamin D [25(OH)D] measurement and to assess the commutability of multiple control materials among liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. METHODS: Serum 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] together with spiked internal standards were extracted with a one-step approach and then analyzed by LC-MS/MS. The commutability assessment for 25(OH)D was conducted according to the Clinical and Laboratory Standards Institute (CLSI) EP14-A3 protocol. 25(OH)D concentrations in 5 levels of unprocessed serum pools, 7 levels of serum pools spiked with 25(OH)D3 or 25(OH)D2, 3 levels of commercial control materials, 2 levels of spiked bovine serum, and 4 levels of external quality assessment (EQA) materials were measured along with 30 single-donor samples using the candidate reference method and two routine LC-MS/MS methods. RESULTS: The candidate reference method could separate 25(OH)D2 and 25(OH)D3 from 14 potential interfering compounds completely within a 9-min analysis time. Good method precision was obtained, and measurement results on certified reference material NIST SRM 972a were within the uncertainty of the certified values. All candidate materials were assessed commutable for LC-MS/MS methods. CONCLUSIONS: The candidate reference method for serum 25(OH)D measurement is precise, accurate, and robust against interferences and can provide an accuracy base for routine methods. The multiple alternative control materials with commutability among LC-MS/MS methods will facilitate the further standardization for serum 25(OH)D measurement.

Missing-Sheds Granularity Estimation of Glass Insulators Using Deep Neural Networks Based on Optical Imaging.

Insulator defect detection is an important task in inspecting overhead transmission lines. However, the surrounding environment is complex, and the detection accuracy of traditional image processing algorithms is low. Therefore, insulator defect detection is still mainly performed manually. In order to improve this situation, we proposed an insulator defect detection method called INSU-YOLO based on deep neural networks. Overexposure points in the image will interfere with insulator detection, so we used image augment to reduce noise and extract the edge information of the insulator. Based on an attention mechanism, we introduced a structure called attention-block where the backbone extracts the feature map, and this aims to improve the ability of our method to detect insulators. Insulators have a variety of specifications, and the location and granularity of defects are also different. Therefore, we proposed an adaptive threat estimation method based on the area ratio between the entire insulator and the defect area. In addition, in order to solve the problem of data shortage, we established a dataset called InsuDetSet for model training. Experiments on the InsuDetSet dataset demonstrated that our model outperforms existing state-of-the-art models regarding both the detection box and speed.

Transmission Line Vibration Damper Detection Using Multi-Granularity Conditional Generative Adversarial Nets Based on UAV Inspection Images.

The vibration dampers can eliminate the galloping phenomenon of transmission lines caused by the wind. The detection of vibration dampers based on visual technology is an important issue. Current CNN-based methods struggle to meet the requirements of real-time detection. Therefore, the current vibration damper detection work has mainly been carried out manually. In view of the above situation, we propose a vibration damper detection-image generation model called DamperGAN based on multi-granularity Conditional Generative Adversarial Nets. DamperGAN first generates a low-resolution detection result image based on a coarse-grained module, then uses Monte Carlo search to mine the latent information in the low-resolution image, and finally injects this information into a fine-grained module through an attention mechanism to output high-resolution images and penalize poor intermediate information. At the same time, we propose a multi-level discriminator based on the multi-task learning mechanism to improve the discriminator's discriminative ability and promote the generator to output better images. Finally, experiments on the self-built DamperGenSet dataset show that the images generated by our model are superior to the current mainstream baselines in both resolution and quality.

Transmission Line Vibration Damper Detection Using Deep Neural Networks Based on UAV Remote Sensing Image.

Vibration dampers can greatly eliminate the galloping phenomenon of overhead transmission wires caused by wind. The detection of vibration dampers based on visual technology is an important issue. The current vibration damper detection work is mainly carried out manually. In view of the above situation, this article proposes a vibration damper detection model named DamperYOLO based on the one-stage framework in object detection. DamperYOLO first uses a Canny operator to smooth the overexposed points of the input image and extract edge features, then selectees ResNet101 as the backbone of the framework to improve the detection speed, and finally injects edge features into backbone through an attention mechanism. At the same time, an FPN-based feature fusion network is used to provide feature maps of multiple resolutions. In addition, we built a vibration damper detection dataset named DamperDetSet based on UAV cruise images. Multiple sets of experiments on self-built DamperDetSet dataset prove that our model reaches state-of-the-art level in terms of accuracy and test speed and meets the standard of real-time output of high-accuracy test results.

Measurement of serum 17-hydroxyprogesterone using isotope dilution liquid chromatography-tandem mass spectrometry candidate reference method and evaluation of the performance for three routine methods.

OBJECTIVES: Accurate measurements of serum 17-hydroxyprogesterone (17OHP) are essential for diagnosis and treatment monitoring for congenital adrenal hyperplasia patients. The performance of serum 17OHP routine methods remains highly variable that calls for a candidate reference measurement procedure (cRMP) to improve the standardization of serum 17OHP measurements. METHODS: Serum samples spiked with internal standards were extracted with a combination of solid-phase extraction and liquid-liquid extraction. The 17OHP was quantified by the isotope dilution coupled with liquid chromatography/tandem mass spectrometry (ID-LC/MS/MS) with electrospray ionization in positive ion mode. Nine structural analogs of 17OHP were evaluated for interferences. The precision and analytical recovery were assessed. Twenty native and 40 spiked serum for performance evaluation were measured by the cRMP and two clinical LC/MS routine methods. RESULTS: No apparent interferences were found with the 17OHP measurement. The within-run, between-run, and total precision for our method were 0.4-0.8%, 0.6-2.0%, and 1.0-2.1% for four pooled serum (2.46-102.72 nmol/L), respectively. The recoveries of added 17OHP were 100.0-100.2%. For the performance of two LC/MS routine methods, they showed relative deviation ranges of -22.1 to 1.1% and -6.7 to 12.8%, respectively. CONCLUSIONS: We developed and validated a reliable serum 17OHP method using ID-LC/MS/MS. The desirable accuracy and precision of this method enable it to serve as a promising cRMP to improve the standardization for serum 17OHP routine measurements.

The effect of transcutaneous electrical nerve stimulation (TENS) on pain control and phenylethanolamine-N-methyltransferase (PNMT) gene expression after cesarean section.

Transcutaneous electrical nerve stimulation (TENS) is one of the non-pharmacological methods of pain relief that has been able to reduce pain by 70 to 90% in postoperative pain control. This study aimed to determine the effect of TENS on pain control after cesarean section and its effect on PNMT gene expression. For this purpose, a double-blind randomized clinical trial was performed on 70 Chinese patients with elective cesarean section. Patients were divided into case and control groups. In the case group, TENS and analgesic drugs were used to relieve pain, and in the control group, the only analgesic drug was used. Then the severity of pain, recurrence of pain attacks, the number of analgesic drugs used and the amount of analgesic drug used in the first 24 hours after surgery were evaluated and compared. Blood samples were also taken from patients to evaluate PNMT gene expression. The semi-quantitative RT-PCR was used to study changes in gene expression. The results showed that the group treated with TENS had less pain intensity and less recurrence of pain attacks than the group that received only analgesic medication. Also, the frequency of analgesic drug use and its dose in the TENS group were significantly lower than in the control group. TENS, on the other hand, has been able to greatly reduce the expression of the PNMT gene, which is produced during times of stress. Therefore, it is recommended that TENS be used as a non-invasive and non-pharmacological adjuvant effective in reducing pain after cesarean section.

Preconditioning with Cathodal High-Definition Transcranial Direct Current Stimulation Sensitizes the Primary Motor Cortex to Subsequent Intermittent Theta Burst Stimulation.

Noninvasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can induce long-term potentiation-like facilitation, but whether the combination of TMS and tDCS has additive effects is unclear. To address this issue, in this randomized crossover study, we investigated the effect of preconditioning with cathodal high-definition (HD) tDCS on intermittent theta burst stimulation- (iTBS-) induced plasticity in the left motor cortex. A total of 24 healthy volunteers received preconditioning with cathodal HD-tDCS or sham intervention prior to iTBS in a random order with a washout period of 1 week. The amplitude of motor evoked potentials (MEPs) was measured at baseline and at several time points (5, 10, 15, and 30 min) after iTBS to determine the effects of the intervention on cortical plasticity. Preconditioning with cathodal HD-tDCS followed by iTBS showed a greater increase in MEP amplitude than sham cathodal HD-tDCS preconditioning and iTBS at each time postintervention point, with longer-lasting after-effects on cortical excitability. These results demonstrate that preintervention with cathodal HD-tDCS primes the motor cortex for long-term potentiation induced by iTBS and is a potential strategy for improving the clinical outcome to guide therapeutic decisions.

"Colloid-Atom Duality" in the Assembly Dynamics of Concave Gold Nanoarrows.

We use liquid-phase transmission electron microscopy (TEM) to study self-assembly dynamics of charged gold nanoarrows (GNAs), which reveal an unexpected "colloid-atom duality". On one hand, they assemble following the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory for colloids when van der Waals attraction overruns slightly screened electrostatic repulsion. Due to concaveness in shape, GNAs adopt zipper motifs with lateral offset in their assembly matching with our modeling of inter-GNA interaction, which form into unconventional structures resembling degenerate crystals. On the other hand, further screening of electrostatic repulsion leads to merging of clusters assembled from GNAs, reminiscent of the coalescence growth mode in atomic crystals driven by minimization of surface energy, as we measure from the surface fluctuation of clusters. Liquid-phase TEM captures the initial formation of highly curved necks bridging the two clusters. Analysis of the real-time evolution of neck width illustrates the first-time observation of coalescence in colloidal assemblies facilitated by rapid surface diffusion of GNAs. We attribute the duality to the confluence of factors (e.g., nanoscale colloidal interaction, diffusional dynamics) that we access by liquid-phase TEM, taking turns to dominate at different conditions, which is potentially generic to the nanoscale. The atom aspect, in particular, can inspire utilization of atomic crystal synthesis strategies to encode structure and dynamics in nanoscale assembly.

TGFß attenuates cartilage extracellular matrix degradation via enhancing FBXO6-mediated MMP14 ubiquitination.

OBJECTIVES: FBXO6, a component of the ubiquitin E3 ligases, has been shown to bind high mannose N-linked glycoproteins and act as ubiquitin ligase subunits. Most proteins in the secretory pathway, such as matrix metalloproteinases, are modified with N-glycans and play important roles in the development of osteoarthritis (OA). However, whether FBXO6 exerts regulatory effects on the pathogenesis of OA remains undefined. METHODS: The expression of FBXO6 was examined in the cartilage of human and multiple mouse OA models. The role of FBXO6 in cartilage degeneration was analysed with global FBXO6-/- mice, transgenic Col2a1-CreERT2;FBXO6f/f mice. The FBXO6 interacting partner MMP14 and its regulatory transcriptional factor SMAD2/3 were identified and validated in different pathological models as well as SMAD2-/- mice. RESULTS: The expression of FBXO6 decreased in the cartilage from human OA samples, anterior cruciate ligament transaction (ACLT) -induced OA samples, spontaneous OA STR/ort samples and aged mice samples. Global knockout or conditional knockout of FBXO6 in cartilage promoted experimental OA process. The molecular mechanism study revealed that FBXO6 decreased MMP14 by ubiquitination and degradation, leading to inhibited proteolytic activation of MMP13. Interestingly, FBXO6 expression is regulated by transforming growth factor ß (TGFß)-SMAD2/3 signalling pathway. Therefore, the overexpression of FBXO6 protected mice from post-injury OA development. CONCLUSIONS: TGFß-SMAD2/3 signalling pathway suppressed MMP13 activation by upregulating of FBXO6 transcription and consequently promoting MMP14 proteasomal degradation. Inducement of FBXO6 expression in OA cartilage might provide a promising OA therapeutic strategy.