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Abstract Background Traditional genomic profiling and mutation analysis of single cells like Circulating Tumor Cells (CTCs) fails to capture post-translational and functional alterations of proteins, often leading to limited treatment efficacy. To overcome this gap, we developed a miniaturized ‘protein analysis on the single cell level’ workflow—baptized ZeptoCTC. It integrates established technologies for single-cell isolation with sensitive Reverse Phase Protein Array (RPPA) analysis, thus enabling the comprehensive assessment of multiple protein expression and activation in individual CTCs. Methods The ZeptoCTC workflow involves several critical steps. Firstly, individual cells are labeled and isolated. This is followed by cell lysis and the printing of true single cell lysate preparations onto a ZeptoChip using a modified micromanipulator, CellCelector™. The printed lysates then undergo fluorescence immunoassay RPPA protein detection using a ZeptoReader. Finally, signal quantification is carried out with Image J software, ensuring precise measurement of multiple protein levels. Results The efficacy of ZeptoCTC was demonstrated through various applications. Initially, it was used for measuring EpCAM protein expression, a standard marker for CTC detection, revealing higher levels in single MCF-7 over MDA-MB-231 tumor cells. Furthermore, in Capivasertib (Akt-inhibitor)-treated MCF-7 single cells, ZeptoCTC detected a 2-fold increase in the pAkt/Akt ratio compared to control cells, and confirmed co-performed bulk-cell western blot analysis results. Notably, when applied to individual CTCs from metastasized breast cancer patients, ZeptoCTC revealed significant differences in protein activation levels, particularly in measured pAkt and pErk levels, compared to patient-matched WBCs. Moreover, it successfully differentiated between CTCs from patients with different Akt1 genotypes, highlighting its potential to determine the activation status of druggable cancer driving proteins for individual and targeted treatment decision making. Conclusions The ZeptoCTC workflow represents a valuable tool in single cell cancer research, crucial for personalized medicine. It permits detailed analysis of key proteins and their activation status of targeted, cancer-driven signaling pathways in single cell samples, aiding in understanding tumor response, progression, and treatment efficacy beyond bulk analysis. The method significantly advances clinical investigations in cancer, improving treatment precision and effectiveness. The workflow will be applicable to protein analysis on other types of single cells like relevant in stem cell, neuropathology and hemopoietic cell research.

Abstract Background Meeting the 24-hour movement behavior (24-HMB) guideline helps enhance quality of life (QOL) of adolescents. This study aimed to assess the associations between the 24-HMB (physical activity, screen time, sleep) and QOL among adolescents with idiopathic scoliosis. Methods A cross-sectional study was conducted between September 2021 and September 2023. 24-HMB, QOL and demographic variables were collected through a self-reported questionnaire. Linear regression models and stratified analyses were used to explore statistical associations between the 24-HMB and QOL. Results A total of 1073 participants aged 10–18 years with a spinal Cobb angle between 10° and 40° were included. Overall, 20 participants (1.9%) met all three behavioral guidelines, and 272 participants (25.3%) met none. Compared to those who did not meet any of the guidelines, adolescents meeting both screen time and sleep duration (β = 4.10, 95% CI: 2.02–6.18, P

Abstract Background Human health is a complex, dynamic concept encompassing a spectrum of states influenced by genetic, environmental, physiological, and psychological factors. Traditional Chinese Medicine categorizes health into nine body constitutional types, each reflecting unique balances or imbalances in vital energies, influencing physical, mental, and emotional states. Advances in machine learning models offer promising avenues for diagnosing conditions like Alzheimer's, dementia, and respiratory diseases by analyzing speech patterns, enabling complementary non-invasive disease diagnosis. The study aims to use speech audio to identify subhealth populations characterized by unbalanced constitution types. Methods Participants, aged 18–45, were selected from the Acoustic Study of Health. Audio recordings were collected using ATR2500X-USB microphones and Praat software. Exclusion criteria included recent illness, dental issues, and specific medical histories. The audio data were preprocessed to Mel-frequency cepstral coefficients (MFCCs) for model training. Three deep learning models—1-Dimensional Convolution Network (Conv1D), 2-Dimensional Convolution Network (Conv2D), and Long Short-Term Memory (LSTM)—were implemented using Python to classify health status. Saliency maps were generated to provide model explainability. Results The study used 1,378 recordings from balanced (healthy) and 1,413 from unbalanced (subhealth) types. The Conv1D model achieved a training accuracy of 91.91% and validation accuracy of 84.19%. The Conv2D model had 96.19% training accuracy and 84.93% validation accuracy. The LSTM model showed 92.79% training accuracy and 87.13% validation accuracy, with early signs of overfitting. AUC scores were 0.92 and 0.94 (Conv1D), 0.99 (Conv2D), and 0.97 (LSTM). All models demonstrated robust performance, with Conv2D excelling in discrimination accuracy. Conclusions The deep learning classification of human speech audio for health status using body constitution types showed promising results with Conv1D, Conv2D, and LSTM models. Analysis of ROC curves, training accuracy, and validation accuracy showed all models robustly distinguished between balanced and unbalanced constitution types. Conv2D excelled with good accuracy, while Conv1D and LSTM also performed well, affirming their reliability. The study integrates constitution theory and deep learning technologies to classify subhealth populations using noninvasive approach, thereby promoting personalized medicine and early intervention strategies.

Abstract Though plenty of research has been conducted to improve the low intrinsic electronic conductivity of NASICON‐structured NaTi2(PO4)3 (NTP), realizing sodium‐ion batteries with high areal/volumetric capacity still remains a formidable challenge. Herein, a multiscale design from anode material to electrode structure is proposed to obtain a gadolinium‐ion‐doped and carbon‐coated NTP composite electrode (NTP‐Gd‐C), in which gadolinium ion doping, oxygen vacancy, optimized structure, N‐doped carbon coating, and bridging on the three‐dimensional network are simultaneously achieved. In the whole electrode, the excellent hierarchical electronic/ionic conductivity and structural stability are simultaneously improved via the synergistic optimization of NTP‐Gd‐C. As a result, excellent electrochemical performances of NTP‐Gd‐C electrode with a high areal/volumetric capacity of 1.0 mAh cm−2/142.8 mAh cm−3, high rate capability (58.3 mAh g−1 at 200 C), long cycle life (ultralow capacity fading of 0.004% per cycle under 10,000 cycles), and wide‐temperature electrochemical performances (97.0 mAh g−1 at 2 C under −20°C) are achieved. Moreover, the NTP‐Gd‐C//Na3V2(PO4)3/C full cell also delivers an excellent rate capacity of 42.0 mAh g−1 at 200 C and long‐term high‐capacity retention of 66.2% after 4000 cycles at 20 C.

Lixiahe Plain's local water resources need to be evaluated effectively and comprehensively. This study is based on the multisource data from 60 natural water samples, 16 rainfall monitoring stations, and 2 evaporation monitoring stations from 1965 to 2020. Synchronous series representativeness analysis, water quality analysis, and water resource availability estimation are conducted to analyze the spatiotemporal distribution characteristics of rainfall, evaporation, and water quality and calculate the availability of various types of water resources. The results indicate that the spatiotemporal distribution of rainfall and evapotranspiration in the study area is uneven, which increases the threat of local floods and droughts. The quality of the main rivers and lakes in the region is good, and the water quality of the drinking water source area and groundwater reaches and even exceeds Class III water standards. In the year 2020, the total water usage in the research area reached 341 million m3. However, the available sum of surface water resources and transit water availability in 2022 was only 201 million m3, so local water supply needs cannot be easily met. Exploring the water resource characterization model of the Lower Rivers Plain can help in local water resource management and protection. HIGHLIGHTS A comprehensive evaluation of water resources is a prerequisite for securing regional water resource management.; Exploring the water resource characterization model of the Lower Rivers Plain can help in local water resource management and protection.; This study can provide a reference for the comprehensive evaluation and analysis of water resource characteristics in other global water-networked plain areas.;

Abstract Background Unhealthy lifestyle behaviors among adolescents have emerged as a significant public health concern worldwide, however, there is little investigation on the impact of unhealthy behaviors on non-suicidal self-injury (NSSI), suicidal ideation (SI) and suicide attempt (SA). This study aimed to investigate the prevalence of seven unhealthy behaviors as well as their associations with NSSI, SI and SA, and to explore whether the aforementioned associations differ across sex. Methods A total of 74,152 adolescents were included in this study via a multi-stage, stratified cluster, random sampling method in 2021. Information about unhealthy behaviors (insufficient physical activity, current smoking, current drinking, excessive screen time, long homework time, insufficient sleep and unhealthy BMI), NSSI, SI, SA and other demographics was collected. Sampling weights were used to estimate the prevalence, and the weighted logistic regression models were performed. Stratified analyses by sex and sensitive analyses were conducted. Results Overview, the weighted prevalence of adolescents had more than five unhealthy behaviors were 5.2%, with boys showing a higher prevalence than girls (6.5% vs.3.8%). Current smoking, current drinking, excessive screen use, long homework time, insufficient sleep, and unhealthy BMI were significantly associated with NSSI, SI and SA. Moreover, adolescents with high lifestyle risk scores were associated with an increased risk of NSSI (5–7 vs. 0: OR 6.38, 95% CI 5.24–7.77), SI (5–7 vs. 0: OR 7.67, 95% CI 6.35–9.25), and SA (5–7 vs. 0: OR 9.57, 95% CI 6.95–13.17). Significant sex differences were found in the associations of unhealthy behaviors with NSSI, SI and SA. Conclusion Unhealthy behaviors are quite common among Chinese adolescents. Adolescents with multiple unhealthy behaviors are associated with increased risks of NSSI, SI, and SA. The implementation of school and family-based interventions to promote healthy lifestyles is recommended as a preventive measure against self-injurious behavior and suicidality in adolescents.

Abstract Background Peutz-Jeghers syndrome (PJS), an autosomal dominant multiple cancerous disorder, is clinically characterized by mucocutaneous macules and multiple gastrointestinal hamartomatous polyps. Gastric-type endocervical adenocarcinoma (G-EAC), a special subtype of cervical adenocarcinoma with non-specific symptoms and signs, is known to occur in approximately 11% of female patients with PJS. Case presentation Here, we report a case of PJS in a 24-year-old female with multiple mucocutaneous black macules who complained of vaginal discharge and menorrhagia. Moreover, we first described the multimodal ultrasonographical manifestations of PJS-correlated G-EAC. The three-dimensional reconstructed view of G-EAC on 3D realisticVue exhibited a distinctive “cosmos pattern” resembling features on magnetic resonance imaging, and the contrast-enhanced ultrasound displayed a “quick-up and slow-down” pattern of the solid components inside the mixed cervical echoes. We reported the multimodal ultrasonographical characteristics of a case of PJS-related G-EAC, as well as reviewed PJS-related literature and medical imaging features and clinical characteristics of G-EAC to provide insight into the feasibility and potential of utilizing multimodal ultrasonography for the diagnosis of G-EAC. Conclusions Multimodal ultrasound can visualize morphological features, solid components inside, and blood supplies of the G-EAC lesion and distinguish the G-EAC lesion from normal adjacent tissues. This facilitates preoperative diagnosis and staging of PJS-related G-EAC, thereby aiding subsequent health and reproductive management for patients with PJS.

Algal blooms, resulting from the overgrowth of algal plankton in water bodies, pose significant environmental problems and necessitate effective remote sensing methods for monitoring. In recent years, Global Navigation Satellite System–Reflectometry (GNSS-R) has rapidly advanced and made notable contributions to many surface observation fields, providing new means for identifying algal blooms. Additionally, meteorological parameters such as temperature and wind speed, key factors in the occurrence of algal blooms, can aid in their identification. This paper utilized Cyclone GNSS (CYGNSS) data, Sentinel-3 OLCI data, and ECMWF Re-Analysis-5 meteorological data to retrieve Chlorophyll-a values. Machine learning algorithms were then employed to classify algal blooms for early warning based on Chlorophyll-a concentration. Experiments and validations were conducted from May 2023 to September 2023 in the Hongze Lake region of China. The results indicate that classification and early warning of algal blooms based on CYGNSS data produced reliable results. The ability of CYGNSS data to accurately reflect the severity of algal blooms opens new avenues for environmental monitoring and management.

Abstract The interaction between nitrogen monoxide (NO) and organic peroxy radicals (RO2) greatly impacts the formation of highly oxygenated organic molecules (HOM), the key precursors of secondary organic aerosols. It has been thought that HOM production can be significantly suppressed by NO even at low concentrations. Here, we perform dedicated experiments focusing on HOM formation from monoterpenes at low NO concentrations (0 – 82 pptv). We demonstrate that such low NO can enhance HOM production by modulating the RO2 loss and favoring the formation of alkoxy radicals that can continue to autoxidize through isomerization. These insights suggest that HOM yields from typical boreal forest emissions can vary between 2.5%-6.5%, and HOM formation will not be completely inhibited even at high NO concentrations. Our findings challenge the notion that NO monotonically reduces HOM yields by extending the knowledge of RO2-NO interactions to the low-NO regime. This represents a major advance towards an accurate assessment of HOM budgets, especially in low-NO environments, which prevails in the pre-industrial atmosphere, pristine areas, and the upper boundary layer.

Pelvic floor muscle training (PFMT) reduces the symptoms in women with pelvic floor dysfunction (PFD); however, the optimal initial timing for secondary prevention of PFD by PFMT is not clear. To identify the optimal timing in Asian primiparas with vaginal delivery, bladder neck descent (BND), levator hiatus areas, and levator hiatus distensibility and contractility were assessed in 26 nulliparous women at 36 weeks of gestation and at 2, 4, 6, and 12 weeks postpartum. We found that BND increased significantly from 2 weeks onwards until 6 weeks postpartum (p = 0.004); the levator hiatus area at rest and contraction both showed the largest value at 2 weeks postpartum (p = 0.005 and p < 0.005 respectively), followed by a continuous decrease; the hiatus area during Valsalva manoeuvre, and the levator hiatus distensibility and contractility showed the lowest value at 2 weeks postpartum, followed by a continuous increase; the changes in BND showed no correlation with the changes in distensibility or hiatus area during Valsalva manoeuvre (p = 0.073 and 0.590 respectively). In Asian primiparas with vaginal delivery, the recovery of levator hiatus and bladder neck mobility begins at 2 and 6 weeks, respectively. This information could be useful in defining the best time to begin PFMT for secondary prevention of postpartum PFD in Asian primiparous women.IMPACT STATEMENT What is already known on this subject? Pelvic floor muscle training (PFMT) helps to reduce symptoms of pelvic floor dysfunction (PFD), however, there are no clear time strategies for the secondary prevention of PFD by PFMT in Asian primiparas with vaginal delivery. What do the results of this study add? This study was the first longitudinal study in Asian primipara to investigate the natural regeneration of pelvic floor functions in the early postpartum period by intensively monitoring the bladder neck mobility and levator hiatus dimensions at multiple time points. We found that bladder neck descent (BND) increased significantly from 2 weeks onwards until 6 weeks postpartum; the levator hiatus area at rest and contraction both showed the largest value at 2 weeks postpartum, followed by a continuous decrease; the hiatus area during Valsalva manoeuvre, and the levator hiatus distensibility and contractility showed the lowest value at 2 weeks postpartum, followed by a continuous increase; the changes in BND showed no correlation with the changes in distensibility or hiatus area during Valsalva manoeuvre. What are the implications of these findings for clinical practice and/or further research? Our study suggested that in Asian primipara, the recovery of bladder neck mobility after vaginal delivery begins at 6 weeks postpartum, while the levator hiatus muscle begins to recover within the first 2 weeks postpartum. Therefore, it could be useful in deciding the best time to start PFMT for secondary prevention of postpartum PFD in Asian primiparous women.

Abstract Background Root development and function have central roles in plant adaptation to the environment. The modification of root traits has additionally been a major driver of crop performance since the green revolution; however, the molecular underpinnings and the regulatory programmes defining root development and response to environmental stress remain largely unknown. Single-cell reconstruction of gene regulatory programmes provides an important tool to understand the cellular phenotypic variation in complex tissues and their response to endogenous and environmental stimuli. While single-cell transcriptomes of several plant organs have been elucidated, the underlying chromatin landscapes associated with cell type-specific gene expression remain largely unexplored. Results To comprehensively delineate chromatin accessibility during root development of an important crop, we applied single-cell ATAC-seq (scATAC-seq) to 46,758 cells from rice root tips under normal and heat stress conditions. Our data revealed cell type-specific accessibility variance across most of the major cell types and allowed us to identify sets of transcription factors which associate with accessible chromatin regions (ACRs). Using root hair differentiation as a model, we demonstrate that chromatin and gene expression dynamics during cell type differentiation correlate in pseudotime analyses. In addition to developmental trajectories, we describe chromatin responses to heat and identify cell type-specific accessibility changes to this key environmental stimulus. Conclusions We report chromatin landscapes during rice root development at single-cell resolution. Our work provides a framework for the integrative analysis of regulatory dynamics in this important crop organ at single-cell resolution.

Design and preparation of dual-role anode materials with extraordinary performance for rechargeable Li/Na-ion batteries (LIBs/NIBs) remains highly challenging. Herein, three-dimensional (3D) pomegranate-like porous bimetallic NiCo2Se4 spheres with N-doped carbon (termed as NC@NiCo2Se4) are synthesized by solvothermal method and annealing. Microstructure investigations reveal that the NC@NiCo2Se4 spheres include nano-sized NiCo2Se4 particles as inner core and NiCo2Se4 with the modification of thin-walled N-doped carbon layer as inner/outer shell. The bimetallic NC@NiCo2Se4 spheres possess synergistic interaction of Ni/Co atoms to enhance intrinsic conductivity and electrochemical activity, unique pomegranate-like structure with an inner void space and robust shell to mitigation volume expansion, and intimate contact of N-doped carbon layer to improve interface effect and accelerate conversion kinetics. As anode materials, the NC@NiCo2Se4 exhibits superior lithium/sodium storage performances (1401.6 and 794.8 mA h g−1 at current density of 0.5 and 5 A g−1 after 500 cycles for LIBs as well as 433.9 mA h g−1 at 3 A g−1 after 1000 cycles and a high capability of 306.6 mA h g−1 at 20 A g−1 for NIBs). This work represents an impressive strategy for future research of bimetallic selenides as anode materials for advanced high-performance LIBs/NIBs.

Abstract Background The three-dimensional spatial organization of the genome plays important roles in chromatin accessibility and gene expression in multiple biological processes and has been reported to be altered in response to environmental stress. However, the functional changes in spatial genome organization during environmental changes in crop plants are poorly understood. Results Here we perform Hi-C, ATAC-seq, and RNA-seq in two agronomically important rice cultivars, Nipponbare (Nip; Japonica) and 93-11 (Indica), to report a comprehensive profile of nuclear dynamics during heat stress (HS). We show that heat stress affects different levels of chromosome organization, including A/B compartment transition, increase in the size of topologically associated domains, and loss of short-range interactions. The chromatin architectural changes were associated with chromatin accessibility and gene expression changes. Comparative analysis revealed that 93-11 exhibited more dynamic gene expression and chromatin accessibility changes, including HS-related genes, consistent with observed higher HS tolerance in this cultivar. Conclusions Our data uncovered higher-order chromatin architecture as a new layer in understanding transcriptional regulation in response to heat stress in rice.

Primary seed dormancy is acquired during seed development and maturation, which is important for plant fitness and survival. DELAY OF GERMINATION1 (DOG1) plays a critical role in inducing seed dormancy. DOG1 expression increases rapidly during seed development, but the precise mechanism underlying this process remains elusive. In this study, we showed that mutants with a loss or reduced function of the chromatin-remodeling factor PICKLE (PKL) exhibit increased seed dormancy. PKL associates with DOG1 chromatin and inhibits its transcription. We found that PKL physically interacts with LUX ARRHYTHMO (LUX), a member of the evening complex (EC) of the circadian clock. Furthermore, LUX directly binds to a specific coding sequence of DOG1, and DOG1 acts genetically downstream of PKL and LUX. Mutations in either LUX or EARLY FLOWERING3 (ELF3) encoding another member of the EC led to increased DOG1 expression and enhanced seed dormancy. Surprisingly, these phenotypes were abolished when the parent plants were grown under continuous light. In addition, we observed that loss of function of either PKL or LUX decreased H3K27me3 levels at the DOG1 locus. Taken together, our study reveals a regulatory mechanism in which EC proteins coordinate with PKL to transmit circadian signals for directly regulating DOG1 expression and seed dormancy during seed development.

Abstract Among its other biological roles, acetylcholinesterase (AChE, EC 3.1.1.7), encoded by two ace in most insects, catalyses the breakdown of acetylcholine, thereby terminating synaptic transmission. ace1 encodes the synaptic enzyme and ace2 has other essential actions in many insect species, such as Chilo suppressalis and Plutella xylostella. The silkworm, Bombyx mori, has been domesticated for more than two thousand years and its aces have no history of pesticide exposure. Here, we investigated the functional differences between two ace genes, BmAce1 and BmAce2, in the silkworm. qPCR analysis indicated that BmAce1 is highly expressed in muscle and BmAce2 is more ubiquitously expressed among tissues and enriched in the head. Both genes were separately suppressed using chemically synthesized siRNAs. The mRNA abundance of the two ace genes was significantly reduced to about 13% – 75% of the control levels after siRNA injection. The AChE activities were decreased to 32% to 85% of control levels. Silencing BmAce2 resulted in about 26% mortality, faster and higher than the 20% in the siBmAce1-treated group. Silencing BmAce1 impacted motor control and development to a greater extent than silencing BmAce2, although both treatment groups suffered motor disability, slowed development and reduced cocoons. Both genes have essential, differing biological significance.

When a DC line fault happens, the converter will be blocked instantly. This leads to an interruption of power transmission and influences the stability of DC and AC systems. To avoid the blocking of converters, this paper presents a novel protection scheme for VSC-HVDC system, which consists fault isolation and auto-reclosing of DC circuit breaker (DCCB). First, this paper coordinates the protective actions of converters and DCCB. The DC line fault is cut immediately by DCCB while the blocking signal of converter is isolated during the fault. Second, since the faults of long overhead transmission DC lines are mostly transient, an auto-reclosing strategy is developed. The emphasise of this part, which includes fault discrimination and time sequences, between DCCB and converter is elaborated, and the value of reclosing delay is derived by analysing the charging and discharging characteristics of capacitor paralleled with converter. Finally, the protection scheme is evaluated by overcurrent, overvoltage, and recovery time of DC system, and simulation results of a point-to-point VSC-HVDC transmission system proves its validity.

Targeted therapy has become the preferred approach to treat most cancers, including metastatic breast cancer. Using liquid biopsies, which can act as a dynamic diagnostic tool, is an appealing concept to identify effective therapies. In order to identify mutations from circulating tumor cells (CTCs) on single cell level, we have developed a multiplex PCR-based next generation sequencing-panel. The CTCs were enriched using the CellSearch system and isolated by micromanipulation followed by whole genome amplification of their DNA. Afterwards, mutation hotspot regions in the PIK3CA, the ESR1, the AKT1, and the ERBB2 genes were amplified and barcoded. Sequencing was performed on a MiSeq system. The assay was validated with cells from various cell lines displaying the expected mutations. Mutations that provide the basis for potential targeted therapies were detected in 10 out of 13 patients in all analyzed genes. In four patients, mutations in more than one gene were observed—either in the same cell or in different cells, suggesting the presence of different tumor cell clones, which might be targeted with combination therapies. This assay is a time and cost effective tool to investigate the most relevant genomic positions indicative for targeted therapies in metastatic breast cancer. It can support therapy decision to improve the treatment of cancer patients.

The formation of 1,3-diketones was observed in the reactions of bulky acyl chlorides with methyllithium. The reaction products depend on the steric hindrance around the carbonyl group of the acyl chloride and the electronic effect of the group(s) linked to the carbonyl. When the steric hindrance around the carbonyl group of the acyl chloride is big enough, the 1,3-diketone is the only product. In the case of the moderate hindrance around the carbonyl group of the acyl chloride, a moderate yield of 1,3-diketone is obtained and some tertiary alcohol is generated. When there is no steric hindrance around the carbonyl group of the acyl chloride, the tertiary alcohol is the only product. When the steric hindrance around the carbonyl group is moderate and an electron-donating group is connected to the carbonyl of the acyl chloride, all three products—ketone, 1,3-diketone and tertiary alcohol—can be isolated from the reaction mixture after long reaction times.

Circulating tumor cells (CTCs), potential precursors of most epithelial solid tumors, are mainly enriched by epithelial cell adhesion molecule (EpCAM)-dependent technologies. Hence, these approaches may overlook mesenchymal CTCs, considered highly malignant. Our aim was to establish a workflow to enrich and isolate patient-matched EpCAMhigh and EpCAMlow/negative CTCs within the same blood samples, and to investigate the phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) mutational status within single CTCs. We sequentially processed metastatic breast cancer (MBC) blood samples via CellSearch® (EpCAM-based) and via Parsortix™ (size-based) systems. After enrichment, cells captured in Parsortix™ cassettes were stained in situ for nuclei, cytokeratins, EpCAM and CD45. Afterwards, sorted cells were isolated via CellCelector™ micromanipulator and their genomes were amplified. Lastly, PIK3CA mutational status was analyzed by combining an amplicon-based approach with Sanger sequencing. In 54% of patients′ blood samples both EpCAMhigh and EpCAMlow/negative cells were identified and successfully isolated. High genomic integrity was observed in 8% of amplified genomes of EpCAMlow/negative cells vs. 28% of EpCAMhigh cells suggesting an increased apoptosis in the first CTC-subpopulation. Furthermore, PIK3CA hotspot mutations were detected in both EpCAMhigh and EpCAMlow/negative CTCs. Our workflow is suitable for single CTC analysis, permitting—for the first time—assessment of the heterogeneity of PIK3CA mutational status within patient-matched EpCAMhigh and EpCAMlow/negative CTCs.

The fierce global competition and market turbulence has been forcing the enterprises towards to the integration and intelligence for supply chain management, and the seamless information sharing and collaboration as well as operation agility are the challenges which need to be conquered, in terms of the highly distributed and heterogeneous resources located in separated warehouses. Although a number of works have been done to achieve the aforementioned targets, few of them are able to provide an overall integration and intelligence support for such system management. In this context, a novel intelligent supply chain integration and management system based on Cloud of Things is presented, in order to provide flexible and agile approaches to facilitate the resource sharing and participant collaboration in the whole supply chain life cycle. Furthermore, the enabling technologies, such as intelligent supply chain condition perception, heterogeneous network access convergence, and resource servicisation, are also studied. Finally, a case study together with the prototype system is implemented and demonstrates that the developed system can efficiently realise the integration of supply chain processes in the form of services, and also provide the effective intelligence support for physical resource management, so as to achieve an overall performance assurance for the system operation.

Topological insulator Bi2Te3 nanoplates with hexagonal, triangular and truncated triangular nanostructures have been fabricated with thickness of ∼10 nm by vacuum vapor phase deposition method. The possible formation mechanism of Bi2Te3 nanoplates with different nanostructures has been proposed. We have examined the surface potentials of Bi2Te3 nanoplates using Kelvin probe force microscopy. The surface potential of Bi2Te3 nanoplates is determined to be about 482 mV on the SiO2/Si substrate, 88 mV and -112 mV on the n-doped and p-doped Si (111) substrates, respectively. The surface potential information provides insight into understanding electronic properties of Bi2Te3 nanoplates, which may open a new door to the exploration of the topological insulators.

Two-dimensional MoS2-based materials are considered to be one of the most attractive materials for next-generation nanoelectronics. The electrostatic properties are important in designing and understanding the performance of MoS2-based devices. By using Kelvin probe force microscopy, we show that few-layer MoS2 sheets exhibit uniform surface potential and charge distributions on their surfaces but have relatively lower surface potentials on the edges, folded areas as well as defect grain boundaries.