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Conventional chemotherapy and radiation therapy are often insufficient in eliminating cancer and are accompanied by severe side effects, due to a lack in the specificity of their targeting. Magnetic iron nanowires have made a great contribution to the nanomedicine field because of their low toxicity and ease of manipulation with the magnetic field. Recently, they have been used in magnetic resonance imaging and wireless magnetomechanical and photothermal treatments. The addition of active targeting moieties to these nanowires thus creates a multifunctional tool that can boost therapeutic efficacies through the combination of different treatments toward a specific target. Colon cancer is the third most commonly occurring cancer, and 90 ± 2.5% of colon cancer cells express the glycoprotein CD44. Iron nanowires with an iron oxide surface are biocompatible, multifunctional materials that can be controlled by magnetic fields and heated by laser irradiation. Here, they were functionalized with anti-CD44 antibodies and used in a combination therapy that included magnetomechanical and photothermal treatments on colon cancer cells. The functionalization resulted in a 3-fold increase of nanowire internalization in colon cancer cells compared to control cells and did not affect the antigenicity and magnetic properties. It also increased the efficacy of killing from 35 ± 1% to more than 71 ± 2%, showing that the combination therapy was more effective than individual therapies alone.

In this paper, an optical calibration instrument is proposed for mass production of irradiation angle sensors. A Lambert-based current compensation principle with nonlinear parameter identification tools are given to improve the precision of sensor-specific characteristic functions through eliminating the adversary effects of indoor light attenuation and manufacturing defects. The newly designed instrument, endowed with the proposed tools, is a smart device that is automatic, fast, efficient, and accurate. Outdoor experimental results show that the instrument calibrates the sensor in a good accuracy up to 0.23° at the presence of 16° manufacture errors of inclines. Therefore, the instrument is promising in mass production in terms of intelligent manufacture process.

Background The aim of this study was to investigate the predictive value of early changes in 18F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) during fulvestrant 500 mg therapy in patients with estrogen receptor (ER)-positive metastatic breast cancer. Materials and Methods Patients underwent 18F-FES PET/CT scans at both baseline (scan 1) and day 28 (scan 2). The maximum standardized uptake value (SUVmax) of all metastatic sites was determined in each scan, and the percentage reduction in SUVmax (ΔSUVmax) was calculated as [(SUVmax on scan 1-SUVmax on scan 2)/ SUVmax on scan 1] * 100%. Results In total, 294 18F-FES-positive lesions from 36 patients were identified. The 18F-FES SUVmax varied widely among lesions (median 5.7; range 1.8–32.4) and patients (median 5.1; range 2.5–13.2). After treatment, the median SUVmax among lesions and patients was 2.1 and 2.1, respectively. The ΔSUVmax ranged from −5.1% to 100%, with a median reduction of 61.3%. Using receiver operating characteristic analysis, the optimal cutoff point to discriminate patients who could derive clinical benefit from fulvestrant was determined to be 38.0%. Patients with a median ΔSUVmax ≥38.0% experienced significantly longer progression-free survival (PFS) than those with ΔSUVmax Conclusion Changes in SUVmax measured by serial imaging of 18F-FES PET/CT could be used early to predict PFS benefit in patients receiving fulvestrant therapy. Implications for Practice The aim of this study was to evaluate the role of 18F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) in predicting response to fulvestrant 500 mg therapy in patients with hormone receptor-positive/human epidermal growth receptor 2–negative metastatic breast cancer. This study highlights the utility of FES PET/CT as a predictive factor to discriminate patients who might benefit from fulvestrant. Moreover, these findings showed that this molecular imaging technique might be a potential tool for physicians to make individualized treatment strategies.

The rewritable bistable memory characteristics have been studied in polymethyl methacrylate (PMMA) and carboxylated multi-walled carbon nanotubes (CNT) composite films. The sandwich structure FTO/PMMA + CNTs/Ag devices were prepared by spin coating and vacuum evaporation process. The device exhibited rewritable bistable resistive switching with switch-on voltage of ~ − 1.5 V, switch-off voltage of ~ 3.4 V, and a high ON/OFF ratio almost of 105. The rewritable behavior of the FTO/PMMA + CNTs/Ag device has been investigated by the endurance test, retention test, and the write-read-erase-reread multiple-cycle tests. The FTO/PMMA + CNTs/Ag device exhibited good retention performance for 2 × 105 s and underwent 104 read pulses. The conduction mechanism in ON state obeys Ohmic conduction; simultaneously, for OFF state, trap-limited space-charge limited conduction was discovered to be the dominant conduction mechanism.

Lunar exploration is a significant process to unravel the evolutionary history of the Earth-Moon system and the pivotal foundation for the exploration of the solar system. A total of 49,161 articles recorded in a comprehensive online literature database between 1959 and 2018 were reviewed to address the development of lunar science in six aspects: publication output volume, keywords, journals, authorship, collaboration, and national output efficiency. The development of lunar science experienced rise and fall corresponding to a log-linearized model that could be clearly divided into three stages: space race (1959-1977), silent stage (1978-1996) and renaissance (1997-2018). Keywords extracted from publications as reliable predictors of multidiscipline showed that the well-developed disciplines of lunar science were astronomy, space engineering, earth and planetary science, while other disciplines played important roles in different stages. Researchers had become cooperative rather than independent in publishing in the past sixty years. Countries with higher average annual GDP contributed more to the development of lunar science. The findings of this work help scholars comprehend the development of lunar science for the past, present and future.

The tubular structural car body of high-speed trains with lightweight design generally results in a low diamond deformation modal frequency, which deteriorates significantly both the lateral and vertical vibrations of the car body. To increase the diamond deformation modal frequency of the car body, the structural optimization and modal sensitivity optimization of the car body based on sensitivity analysis are proposed. The former starts with the analysis of the mode shape deformation characteristics; in the latter case, the modal strain energy verification is considered and the influence of the threshold values of sensitivity on the modal frequency optimization are studied. Results show that by increasing the spacing of the inner and outer panels of the side wall from 47 mm to 65 mm and optimizing the thicknesses of 16 components of the car body, the diamond deformation modal frequency of the fully-equipped car body can be enhanced from 8.7 Hz to 10.31 Hz, while ensuring the lightweight requirement without loss in car body strength.

As a cell proliferation biomarker, Ki-67 is principally used in ER+/HER2− breast cancer. However, the importance and the best cutoff point of Ki-67 in triple-negative breast cancer (TNBC) remains unclear and was evaluated in this study.A total of 1800 patients with early invasive TNBC between 2011 and 2016 at Fudan University Shanghai Cancer Center were consecutively recruited for this study. The optimal cutoff for Ki-67 was assessed by Cutoff Finder. Propensity score matching (PSM, ratio = 1:2) was performed to match the Ki-67low group with the Ki-67high group. Overall survival (OS) and disease-free survival (DFS) were compared between the two groups using the Kaplan-Meier method and Cox regression model. The most relevant cutoff value for Ki-67 for prognosis was 30% (p = 0.008). At the cutoff point of 30%, worse DFS and OS were observed in the Ki-67high group. In multivariate analyses, N-stage (p p = 0.038), and Ki-67 at the 30% threshold (p = 0.020) were independently linked to OS. In subgroup analysis, Ki-67 cutoff at 30% had prognostic and predictive potential for DFS with either tumor size ≤2 cm (p = 0.008) or lymph node-negative (N−) (p = 0.038) and especially with T1N0M0 (stage I) TNBCs. For 945 N− TNBC patients, adjuvant chemotherapy (CT) was associated with better OS in the Ki-67high group (p = 0.017) than in the Ki-67low group (p = 0.875). For stage I/Ki-67low patients, adjuvant CT did not affect DFS (p = 0.248). Thus, Ki-67 cutoff at 30% had early independent prognostic and predictive potential for OS and DFS in TNBCs, and Ki-67 > 30% was significantly associated with worse prognosis, especially for stage I patients. For stage I/Ki-67low TNBC patients, the advantage of CT is unclear, providing the basis for future de-escalation therapy.

Purpose of the Report: Accurate clinical axillary evaluation plays an important role in the diagnosis and treatment planning for early-stage breast cancer (BC). This study aimed to develop a scalable, non-invasive and robust machine learning model for predicting of the pathological node status using dedicated-PET integrating the clinical characteristics in early-stage BC. Materials and Methods: A total of 420 BC patients confirmed by postoperative pathology were retrospectively analyzed. 18F-fluorodeoxyglucose (18F-FDG) Mammi-PET, ultrasound, physical examination, Lymph-PET, and clinical characteristics were analyzed. The least absolute shrinkage and selection operator (LASSO) regression analysis were used in developing prediction models. The characteristic curve (ROC) of the area under receiver-operator (AUC) and DeLong test were used to evaluate and compare the performance of the models. The clinical utility of the models was determined via decision curve analysis (DCA). Then, a nomogram was developed based on the model with the best predictive efficiency and clinical utility and was validated using the calibration plots. Results: A total of 290 patients were enrolled in this study. The AUC of the integrated model diagnosed performance was 0.94 (95% confidence interval (CI), 0.91–0.97) in the training set (n = 203) and 0.93 (95% CI, 0.88–0.99) in the validation set (n = 87) (both p < 0.05). In clinical N0 subgroup, the negative predictive value reached 96.88%, and in clinical N1 subgroup, the positive predictive value reached 92.73%. Conclusions: The use of a machine learning integrated model can greatly improve the true positive and true negative rate of identifying clinical axillary lymph node status in early-stage BC.

An analytical strategy to improve sample throughput with discrete frequency infrared image-based targeted analysis of microplastics using a laser direct infrared chemical imaging system was successfully developed and implemented. Leveraging a quantum cascade laser as a light source, the system could lock the frequency at predetermined wavelengths and use a discrete frequency infrared imaging technique to identify particles with absorption at desired wavelengths. In this way, targeted analysis can be achieved by selectively characterizing these particles. In the concept demonstration study, the targeted analysis was able to identify 87.7% of spiked polyethylene particles by scanning only 20% of the particles in the sample. The technique substantially improves sample throughput by at least a factor of 4 under conditions used. In the tests performed with real environmental samples, the targeted analysis workflow correctly identified eight types of common microplastics by only investigating around 60% of the particles and less than 30% of the sample area. Results obtained demonstrated that this scanning strategy is a game changer to enhance sample throughput in microplastic analysis. The technique has the potential of being applied to other infrared-based analytical platforms.

Phalaenopsis orchids are popular ornamental plants worldwide. The application and optimization of efficient CRISPR-Cas genome editing toolkits in Phalaenopsis greatly accelerate the development of orchid gene function and breeding research. However, these methods are greatly hindered by the deficiency of a rapid screening system. In this study, we established a fast and convenient Phalaenopsis protoplast technology for the identification of functional genome editing tools. Two multiplex genome editing tools, PTG-Cas9-HPG (PTG, polycistronic tRNA-gRNA) system and RMC-Cpf1-HPG (RMC, ribozyme-based multi-crRNA) system, were developed for Phalaenopsis genome editing and further evaluated by established protoplast technology. We successfully detected various editing events comprising substitution and indel at designed target sites of the PDS gene and MADS gene, showing that both PTG-Cas9-HPG and RMC-Cpf1-HPG multiplex genome editing systems are functional in Phalaenopsis. Additionally, by optimizing the promoter that drives Cpf1 expression, we found that Super promoter can significantly improve the editing efficiency of the RMC-Cpf1-HPG system. Altogether, we successfully developed two efficient multiplex genome editing systems, PTG-Cas9-HPG and RMC-Cpf1-HPG, for Phalaenopsis, and the established protoplast-based screening technology provides a valuable foundation for developing more diverse and efficient genome editing toolkits and facilitating the development of orchid precision breeding.

De novo shoot regeneration from a callus plays a crucial role in both plant biotechnology and the fundamental research of plant cell totipotency. Recent studies have revealed many regulatory factors involved in this developmental process. However. our knowledge of the cell heterogeneity and cell fate transition during de novo shoot regeneration is still limited. Here, we performed time-series single-cell transcriptome experiments to reveal the cell heterogeneity and redifferentiation trajectories during the early stage of de novo shoot regeneration. Based on the single-cell transcriptome data of 35,669 cells at five-time points, we successfully determined seven major cell populations in this developmental process and reconstructed the redifferentiation trajectories. We found that all cell populations resembled root identities and undergone gradual cell-fate transitions. In detail, the totipotent callus cells differentiated into pluripotent QC-like cells and then gradually developed into less differentiated cells that have multiple root-like cell identities, such as pericycle-like cells. According to the reconstructed redifferentiation trajectories, we discovered that the canonical regeneration-related genes were dynamically expressed at certain stages of the redifferentiation process. Moreover, we also explored potential transcription factors and regulatory networks that might be involved in this process. The transcription factors detected at the initial stage, QC-like cells, and the end stage provided a valuable resource for future functional verifications. Overall, this dataset offers a unique glimpse into the early stages of de novo shoot regeneration, providing a foundation for a comprehensive analysis of the mechanism of de novo shoot regeneration.

European Union (LIGHTME Grant Agreement No. 814552)

A nonvolatile resistive switching memory device based on active layers of polyvinylcarbazole (PVK) was fabricated by a spin-coating technique, and the electrical characteristics of the devices consisting of SnO2 doped with fluorine (FTO)/PVK/Ag were investigated. The experimental results revealed that the FTO/PVK/Ag device has electrical bistable nonvolatile flash memory behavior. The current remained stable for 2.3 × 103 s in both the ON state and OFF state, and the current in the ON and OFF states of the FTO/PVK/Ag device did not change substantially after 750 pulse read cycles. In addition, based on the electrochemical properties of the PVK, its resistive switching behavior was investigated. This work provides a promising solution for the development of polymer memory devices.

Phase change materials (PCM) are among the leading candidates for the next generation of nonvolatile data storage, and materials along the pseudobinary GeTe–Sb2Te3 line are regularly chosen for the...

Background The Cadherin-11 and PI3K/Akt pathway are increasingly recognized as the potential therapeutic target of osteoarthritis (OA) synovitis. The study aimed to investigate the role of PI3K/Akt signaling pathway in the expression of Cadherin-11 and migration and invasive capacity of fibroblast-like synoviocytes (FLS) of OA patients under stimulation of TNF-α and to explore the effect of the PI3K/Akt inhibitor and Cadherin-11 antibody in the therapy of the collagenase-induced osteoarthritis (CIOA) mice. Methods FLS were primarily cultured from synovium of osteoarthritic patients during total knee arthroplasty. Under the simulation of TNF-α, with or without PI3K/Akt inhibitor LY294002, Cadherin-11 expression was detected by real-time PCR and Western blot, as well as the migration and invasive capacity changes of OA FLS. Cadherin-11 antibody was injected intraarticularly or LY294002 was injected intraperitoneally in CIOA mice to evaluate the changes of synovitis score, cartilage damage, and Cadherin-11 expression. Results TNF-α stimulation increased Cadherin-11 expression at mRNA and protein level in OA FLS and also increased the phosphorylation-dependent activation of Akt. PI3K inhibitor LY294002 attenuated TNF-α-induced overexpression of Cadherin-11 and decreased the invasive capacity of OA FLS. Intraperitoneal injection of PI3K inhibitor LY294002 could decrease the Cadherin-11 protein expression in synovium of CIOA mice, although it has no significant inhibitory effect on synovitis and cartilage damage. Intraarticular injection of Cadherin-11 antibody attenuated the synovitis and cartilage damage in the CIOA joints and decreased Cadherin-11 expression in the synovial lining. Conclusions PI3K/Akt pathway was associated with TNF-α-induced activation of OA FLS, which may involve in the pathogenesis of osteoarthritis. Anti-Cadherin-11 therapy in CIOA mice could attenuate the pathological changes of OA joints.

The aim of our study was to determine whether silencing or overexpression of estrogen receptor β (ERβ) regulates cell proliferation, steroidogenesis, autophagy and signalling pathways in bovine ovarian granulosa cells in vitro. In this study, bovine ovarian granulosa cells (BGCs) were cultured and transfected with ERβ siRNA (si-ERβ) or a plasmid overexpressing ERβ (oe-ERβ), and CCK-8 kit was used to assess cell proliferation. Real-time PCR was used to measure gene transcription. Western blotting was used to measure protein expression, and a specific kit was used to measure the production of steroid hormones. The results showed the expression level of ERβ affects BGC proliferation according to the gene transcription levels of FSHR, CYP19A1, HSD3β1 and STAR and the production of E2 and P4. ERβ was identified as an important nuclear receptor that induced BGC autophagy based on the mRNA and protein expression of autophagy-related genes. Furthermore, the role of ERβ in BGC autophagy was confirmed through treatment with rapamycin (RAPA) or 3-methyladenine (3-MA) in BGCs by cotransfection with si-ERβ or oe-ERβ in BGCs. The results related to AKT/mTOR signalling and phosphorylation suggested that ERβ induces BGC autophagy through attenuating AKT/mTOR signalling. In summary, this study demonstrates that silencing or overexpression of ERβ regulates BGC proliferation and function and induces BGC autophagy by targeting AKT/mTOR signalling. These data reveal a novel regulatory mechanism of autophagy via ERβ and provide insights into the role of autophagy in BGCs.

Purpose Sentinel lymph node biopsy (SLNB) is currently the standard of care in clinically node-negative (cN0) breast cancer. The present study aimed to evaluate the negative predictive value (NPV) of 18F-FDG dedicated lymph node positron emission tomography (LymphPET) in cN0 patients. Methods This is a prospective phase II trial divided into two stages (NCT04072653). In the first stage, cN0 patients underwent axillary LymphPET, followed by SLNB. In the second stage, SLNB was omitted in patients with a negative preoperative axillary assessment after integrating LymphPET. Here, we report the results of the first stage; the primary outcome was the NPV of LymphPET to detect macrometastases of lymph nodes. Results 189 invasive breast cancer patients underwent LymphPET, followed by surgery, with definitive pathological reports. Forty patients had lymph node macrometastasis (LN-macro), and 16 patients had only lymph node micrometastasis (LN-micro). Of the 131 patients who had a negative LymphPET, 16 patients had LN-macro, the NPV was 87.8%. After combining axillary imaging evaluation with ultrasound and LymphPET, 100 patients were found to be both LymphPET and ultrasound negative, 9 patients had LN-macro, the NPV was 91%. Conclusions LymphPET can be used to screen potential patients to avoid SLNB with an NPV >90%. The second stage of the SOAPET trial is ongoing to confirm the safe omission of SLNB according to preoperational axillary evaluation when integrating LymphPET.

Effluent Organic Matter (EfOM) contains a large number of substances that are harmful to both the environment and human health. To avoid the negative effects of organic matter in EfOM, advanced treatment of organic matter is an urgent task. Four typical oxidants (H2O2, PS, PMS, NaClO) and UV-combined treatments were used to treat micro-contaminants in the presence or absence of effluent organic matter (EfOM), because the active radical species produced in these UV-AOPs are highly reactive with organic contaminants. However, the removal efficiency of trace contaminants was greatly affected by the presence of EfOM. The degradation kinetics of two representative micro-contaminants (benzoic acid (BA) and para-chlorobenzoic acid(p-CBA)) was significantly reduced in the presence of EfOM, compared to the degradation kinetics in its absence. Using the method of competitive kinetics, with BA, p-CBA and 1,4-dimethoxybenzene (DMOB) as probes, the radicals (HO·, SO4-·, ClO·) proved to be the key to reaction species in advanced oxidation processes. UV irradiation on EfOM was not primarily responsible for the degradation of micro-contaminants. The second-order rate constants of the EfOM with radicals were determined to be (5.027±0.643)×102(SO4-·), (3.192±0.153)×104 (HO·) and 1.35×106 (ClO·) (mg-C/L)-1·s-1. In addition, this study evaluated the production of three radicals based on the concept of Rct, which can better analyze its reaction mechanism.

SummaryUnderstanding the complex functions of plant leaves requires spatially resolved gene expression profiling with single-cell resolution. However, although in situ gene expression profiling technologies have been developed, this goal has not yet been achieved. Here, we present the first in situ single-cell transcriptome profiling in plant, scStereo-seq (single-cell SpaTial Enhanced REsolution Omics-sequencing), which enabled the bona fide single-cell spatial transcriptome of Arabidopsis leaves. We successfully characterized subtle but significant transcriptomic differences between upper and lower epidermal cells. Furthermore, with high-resolution location information, we discovered the cell type-specific spatial gene expression gradients from main vein to leaf edge. By reconstructing those spatial gradients, we show for the first time the distinct spatial developmental trajectories of vascular cells and guard cells. Our findings show the importance of incorporating spatial information for answering complex biological questions in plant, and scStereo-seq offers a powerful single cell spatially resolved transcriptomic strategy for plant biology.

Soil salinity inhibits seed germination and reduces seedling survival rate, resulting in significant yield reductions in crops. Here, we report the identification of a polyamine oxidase, OsPAO3, conferring salt tolerance at the germination stage in rice (Oryza sativa L.), through map-based cloning approach. OsPAO3 is up-regulated under salt stress at the germination stage and highly expressed in various organs. Overexpression of OsPAO3 increases activity of polyamine oxidases, enhancing the polyamine content in seed coleoptiles. Increased polyamine may lead to the enhance of the activity of ROS-scavenging enzymes to eliminate over-accumulated H

The prognostic value of intensive postoperative bone scan (BS) screening, which is performed in asymptomatic patients with breast cancer (BC) after surgery, remained unclear. Patients diagnosed with BC with bone metastasis (BM) from five medical centers in China during the years 2005–2013 were retrospectively collected. Propensity score matching (PSM) was performed to balance the baseline characteristics. The survival outcomes were overall survival (OS) and overall survival after BM (OSABM). Among 1059 eligible patients, 304 underwent intensive postoperative BS while 755 did not. During a median follow-up of 6.67 years (95%CI 6.45, 7.21), intensive postoperative BS prolonged the median OS by 1.63 years (Log-Rank p = 0.006) and OSABM by 0.66 years (Log-Rank p = 0.002). Intensive postoperative BS was an independent prognostic factor for both OS (adjusted HR 0.77, 95%CI 0.64, 0.93, adjusted p = 0.006) and OSABM (adjusted HR 0.71, 95%CI 0.60, 0.86, adjusted p < 0.001). The prognostic value of intensive postoperative BS was consistently favorable for OS among clinical high-risk patients, including those with ages younger than 50, stage II, histology grade G3 and ER-Her2- subtype. This multicenter real-world study showed that intensive postoperative BS screening improved survival for BC patients with BM and should probably be recommended for postoperative surveillance, especially for patients at clinical high-risk.

Microglia can be activated as proinflammatory (M1) phenotypes and anti-inflammatory (M2) phenotypes after stroke. Parthenolide (PTL) has anti-inflammatory and protective effects on neurological diseases, but until now, the exact mechanisms of these processes after stroke have been unclear. The purpose of this study was to determine the effect of PTL on microglial polarization after stroke and its target for inducing microglial polarization.Triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and neurological evaluation were performed in a focal transient cerebral ischemia rat model. The human microglia exposed to lipopolysaccharide (LPS) was used for in vitro experiments. Microglial polarization was assessed by RT-PCR and immunostaining. Inflammatory cytokine assays and western blotting were used to investigate the molecular mechanisms underlying PTL-mediated microglial polarization in vivo and in vitro.PTL significantly reduced cerebral infarction and neuronal apoptosis in rats with cerebral ischemia, reduced the level of inflammatory factors and alleviated neurological deficits. PTL treatment decreased the expression of microglia/macrophage markers in M1 macrophages and increased the expression of microglia/macrophage markers in M2 macrophages after stroke, which induced the transformation of microglia cells from the M1 phenotype to the M2 phenotype. Furthermore, PTL significantly reduced RhoA/ROCK-NF-κB pathway activity and downregulated the effects of pentanoic acid (ROCK agonist).PTL has been shown to mediate neuroinflammation and protect against ischemic brain injury by regulating microglial polarization via the RhoA/ROCK pathway.

Two hundred twenty-four breast cancer patients with paired tissue and plasma samples were enrolled from 3 clinical centers to evaluate sensitivity and specificity of a digital PCR HER2 amplification assay. All patients were histologically confirmed diagnosis of locally advanced and recurrent or metastatic breast cancer with stage III/IV and had tissue HER2 status determinations using IHC/FISH. For the whole 224 advanced breast cancer patients, the sensitivity between dPCR in plasma and IHC/FISH in tissue samples is 43.75% (42/96), the specificity is 84.38% (108/128) and the overall concordance is 66.96% (150/224). Interestingly, when we looked at stage III, stage IV and recurrent or metastatic breast cancer separately, compared with IHC/FISH in tissue samples, the sensitivity of dPCR in plasma increases from 37.93% (11/29) for stage III to 41.67% (15/36) for stage IV cancer. Recurrent breast cancer patient had an increased sensitivity of 51.61% (16/31). This is consistent with our expectation sensitivity would increase concordantly as tumor burden goes up. On the other hand, specificity decreased from 92.68% (38/41) for stage III to 86.44% (51/59) for stage IV cancer. Recurrent breast cancer patient had a specificity of only 67.86% (19/28). This is, in part, due to inter- and intra-tumor heterogeneity. Many patients determined to be negative for HER2 amplification in tissue biopsy could have HER2 positive tumors at other sites, which was detected by the liquid biopsy. This study suggested the necessity of liquid biopsy for HER2 amplification detection and demonstrated digital PCR can be used as a companion diagnostic tool to determine HER2 amplification status. It also suggested that a liquid biopsy should follow a negative result from tissue biopsy to avoid false negative results especially for late-stage breast cancer patients and ones who experienced relapse or became resistant to current therapy. Future studies should focus on therapeutic effects on patients determined to be HER2 positive through liquid biopsy and collecting additional tissue biopsies to identify HER2 positive tumor when the original tissue biopsy and liquid biopsy don't agree.

Background To better understand the difference between traditional breast-conserving surgery (BCS) and oncoplastic surgery (OPS), we conducted a retrospective cohort study involving breast cancer patients who received neoadjuvant chemotherapy (NAC) and then underwent breast conservation at the Fudan University Shanghai Cancer Center. Methods A retrospective chart review was conducted. All breast cancer patients who received NAC and then underwent traditional BCS or OPS at the Fudan University Shanghai Cancer Center from January 1, 2008, to December 31, 2019, were included. Results Three hundred ninety-nine breast cancer patients received NAC and underwent traditional BCS, and 99 patients underwent OPS. The average age of the patients in the OPS group was younger than that in the BCS group (43 vs 48 years, P = 0.017). The size of the tumor assessed by ultrasonography at baseline in the OPS group was larger than that in the BCS group (31.3 vs 28.1 mm, P = 0.013). The same trend was observed in the clinical T stage and overall staging assessments before the administration of NAC in these 2 groups. Oncoplastic techniques were more frequently applied when tumors were located in areas with relatively few glands, such as the upper inner quadrant. There were no significant differences in the margins and distributions of pathological types and molecular subtypes between these 2 groups. The rates of pathological complete response were similar in the traditional BCS and OPS groups. Conclusions Unlike traditional BCS, in breast cancer patients after NAC, the adoption of oncoplastic techniques makes breast conservation feasible, even in patients with large tumors, late stages, and unfavorable tumor locations.

Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS) mediated by immune cells. The pathogenesis of most autoimmune diseases has some degree of similarity to that of MS, and therefore the study of MS has clinical and scientific significance for other autoimmune diseases as well. As a widely used organic solvent, Methyl Acetate (MA) has a similar structure to acetate which has been shown to be therapeutic in the mouse model of multiple sclerosis. Here we found that MA was effective in reducing the disease severity of Experimental Autoimmune Encephalomyelitis (EAE). Pathological sections showed that MA reduced inflammatory cell infiltration in the CNS and attenuated demyelination in the spinal cord. MA increases the proportion of Th1 cells in the periphery of EAE mice. Further mechanistic studies have demonstrated that MA treatment induces Th1 retention in the peripheral immune system by increasing the expression levels of peripheral Th1-related chemokines CXCR3. CXCL9, CXCL10. In addition, we observed that MA alleviated intestinal inflammation in EAE mice. The data showed that this phenomenon is achieved by enhancing IL-10 and inhibiting IL-6 secretion. Our data indicates that MA might have therapeutic implications for autoimmune diseases such as MS.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by demyelinating neuropathy. The etiology of MS is not yet clear and its treatment remains a major medical challenge. While we search for drugs that can effectively treat experimental autoimmune encephalomyelitis (EAE), the animal model of MS, we also hope to further explore its possible pathogenesis. In the present study, we investigated whether methyl butyrate (MB) could alleviate EAE and its potential mechanisms. In EAE mice, we found that administration of MB was effective in alleviating their clinical signs and improving histopathological manifestations of the CNS. In the CNS and intestinal lamina propria, we observed fewer effector T cells, including Th1 and Th17, in the MB-treated group. MB also increased the proportion of regulatory T cells and the secretion of IL-10 in peripheral immune organs. In vitro, MB led to suppression of Th1 cells and promotion of regulatory T cells in their differentiation. Given that MB had no direct effect on Th17 cell differentiation in vitro, we hypothesized that MB suppressed Th17 cells indirectly by inhibiting the secretion of IL-6, which was later confirmed both in vitro and in vivo. In addition, we found that MB treatment upregulated Maf gene expression in mice, which explained its promotion of IL-10 secretion. The above findings suggest that MB may provide new ideas for the study of the mechanism of MS and have positive implications for new drug development.

Type VI Secretion Systems (T6SSs) are widespread in bacteria and can dictate the development and organisation of polymicrobial ecosystems by mediating contact dependent killing. In Neisseria species, including Neisseria cinerea a commensal of the human respiratory tract, interbacterial contacts are mediated by Type four pili (Tfp) which promote formation of aggregates and govern the spatial dynamics of growing Neisseria microcolonies. Here, we show that N. cinerea expresses a plasmid-encoded T6SS that is active and can limit growth of related pathogens. We explored the impact of Tfp on N. cinerea T6SS-dependent killing within a colony and show that pilus expression by a prey strain enhances susceptibility to T6SS compared to a non-piliated prey, by preventing segregation from a T6SS-wielding attacker. Our findings have important implications for understanding how spatial constraints during contact-dependent antagonism can shape the evolution of microbial communities.

BACKGROUND Elective colorectal cancer (CRC) surgeries offer enhanced surgical outcomes but demand high self-efficacy in prehabilitation and competency in self-care and disease management postsurgery. Conventional strategies to meet perioperative needs have not been pragmatic, and there remains a pressing need for novel technologies that could improve health outcomes. OBJECTIVE The aim of this paper was to describe the development of a smartphone-based interactive CRC self-management enhancement psychosocial program (iCanManage) in order to improve health outcomes among patients who undergo elective CRC surgeries and their family caregivers. METHODS A multidisciplinary international team comprising physicians, specialist nurses, a psychologist, software engineers, academic researchers, cancer survivors, patient ambassadors, and ostomy care medical equipment suppliers was formed to facilitate the development of this patient-centric digital solution. The process occurred in several stages: (1) review of current practice through clinic visits and on-site observations; (2) review of literature and findings from preliminary studies; (3) content development grounded in an underpinning theory; (4) integration of support services; and (5) optimizing user experience through improving interface aesthetics and customization. In our study, 5 participants with CRC performed preliminary assessments on the quality of the developed solution using the 20-item user version of the Mobile App Rating Scale (uMARS), which had good psychometric properties. RESULTS Based on the collected uMARS data, the smartphone app was rated highly for functionality, aesthetics, information quality, and perceived impact, and moderately for engagement and subjective quality. Several limiting factors such as poor agility in the adoption of digital technology and low eHealth literacy were identified despite efforts to promote engagement and ensure ease of use of the mobile app. To overcome such barriers, additional app-training sessions, an instruction manual, and regular telephone calls will be incorporated into the iCanManage program during the trial period. CONCLUSIONS This form of multidisciplinary collaboration is advantageous as it can potentially streamline existing care paths and allow the delivery of more holistic care to the CRC population during the perioperative period. Should the program be found to be effective and sustainable, hospitals adopting this digital solution may achieve better resource allocation and reduce overall health care costs in the long run. CLINICALTRIAL ClinicalTrials.gov NCT04159363; https://clinicaltrials.gov/ct2/show/NCT04159363

The traditional basketball teaching mode cannot meet the needs of students for the basic cooperation of basketball tactics. Therefore, a basic cooperation teaching system of basketball tactics based on artificial neural network is studied and designed. The system has a professional basketball game video tactical learning module. The events in the basketball game video are classified through a convolutional neural network and combined with the explanation of teachers to make the students have an intuitive understanding of the basic cooperation of basketball tactics and then design the basketball game module based on a BP neural network to provide students with an online basketball tactics training platform. Finally, the teacher scores the performance of the actual on-site training students in the basic cooperation of basketball tactics through the tactical scoring module on the system. The results show that after the introduction of global and collective motion patterns, the classification accuracy of the convolutional neural network is improved by 22.48%, which has significant optimization. The average accuracy of basketball game video event classification is 62.35%, and the accuracy of snatch event classification is improved to 95.28%. The recognition rate of the BP neural network combined with momentum gradient descent method is 75%, the number of weight adjustment is less, and the memory is small while ensuring fast running speed. Students who accept the basic basketball tactics cooperation teaching system based on the artificial neural network for basketball teaching have an overall score of 27.99 ± 2.11 points The overall score of exchange defense cooperation was 24.12 ± 2.03, which was higher than that of the control group. The above results show that the basketball tactical basic cooperation teaching system based on the artificial neural network has a good teaching effect in improving students’ basketball tactical basic cooperation ability.

Background Mortality and complications remain high after Acute Type A Aortic Dissection (ATAAD) open surgery, which is associated with coagulation dysfunction. Platelets play an important role in the process of coagulation. This study was to explore the relationship between postoperative platelet counts and postoperative mortality in patients with ATAAD after open aortic repair surgery.Methods Patients with ATAAD who underwent Total Arch Replacement and Frozen Elephant Trunk in Fuwai Hospital from 2011 to 2015 were selected in this study. The perioperative data were collected and sorted through the electronic clinical case system. Multivariate Logistic regression was used to analyze the risk factors for death within three years after surgery.Results A total of 495 patients were included in the analysis. After correction with the confounding factors, postoperative platelets count remained as an independent factor that was associated with lower mortality (OR = 0.918, 95%CI 0.853-0.988, P = 0.023).Conclusions The study indicated that decreased postoperative platelet count may lead to increased mortality, in patients with ATAAD underwent open aortic repair surgery.

Aim: Oat protein-shellac nanoparticles (NPs) were developed as a delivery system for resveratrol to improve bioavailability. Materials & methods: The NPs were prepared from w/w emulsion followed by cold-gelation. In vitro release and cell uptake mechanism of NPs were estimated by HPLC and confocal laser scanning microscopy. In vivo bioavailability and hepatoprotective activity of encapsulated resveratrol were studied using rat models. Results & conclusion: NPs (90–300 nm) protected resveratrol in gastric fluid, while allowing controlled release into small intestine in vitro. The optimized NPs showed improvement in resveratrol cell uptake and transport when compared with free resveratrol. NP-100S increased resveratrol bioavailability up to 72.4%, and the absorbed resveratrol effectively prevented CCl4-induced hepatotoxicity by attenuating oxidative stress.

Blind motion deblurring is one of the most basic and challenging problems in image processing and computer vision. It aims to recover a sharp image from its blurred version knowing nothing about the blur process. Many existing methods use Maximum A Posteriori (MAP) or Expectation Maximization (EM) frameworks to deal with this kind of problems, but they cannot handle well the figh frequency features of natural images. Most recently, deep neural networks have been emerging as a powerful tool for image deblurring. In this paper, we prove that encoder-decoder architecture gives better results for image deblurring tasks. In addition, we propose a novel end-to-end learning model which refines generative adversarial network by many novel training strategies so as to tackle the problem of deblurring. Experimental results show that our model can capture high frequency features well, and the results on benchmark dataset show that proposed model achieves the competitive performance.

We report a piezoelectric mechanism to stop dendrite growth, which enables inherently safe lithium metal battery. For demonstration, a polarized piezoelectric polyvinylidene fluoride (PVDF) film is...

Popular sensors that detect the quadrant of the illumination directions are often inadequate for advanced control systems, e.g., solar trackers and heliostats. We propose a theoretical and technical framework for some sensor-specific characterization tools together with an optical instrument, which makes possible the accurate measurements in terms of the illumination angle and its angular velocity at the presence of the manufacturing errors due to rough manufacturing processes (e.g., forging and casting). In particular, a parameter identification approach is employed to identify four uncertain incline angles of sensor products with the aid of an ingenious and controllable calibration device. The angular velocity of illumination is approximately derived through a one-step backward difference function together with finite impulse response filters to reject the disturbances. The experimental results show that the sensor-specific nonlinear characteristic functions improve the accuracy of the illumination angle measurement yielded by the general nonlinear characteristic functions for the ideal sensors up to 96%, where the measurement precision with 0.07° is achieved.

To investigate whether digital breast tomosynthesis (DBT) and subsequently generated synthesized mammography (SM) images show a better performance than full-field digital mammography (FFDM) images for diagnosing malignant breast lesions. In addition, the radiation doses for SM using different procedures were compared. This prospective study enrolled 212 women (age ≥ 25 years) with clinically suspicious breast lesions. All participants underwent FFDM and DBT with the same breast compression. Finally, 222 lesions were confirmed by pathological analysis. The mammogram results were evaluated according to the BI-RADS criteria and compared with the pathological results. The diagnostic performances, morphological features and average glandular doses (AGDs) were compared. In total, 141 malignant lesions and 81 benign lesions were confirmed by pathological analysis. The overall AGD showed no significant difference between FFDM and DBT. Compared with 2D imaging, the AUC values of FFDM plus DBT and SM plus DBT were both significantly different overall (P = 0.0002) and remained significantly different in dense breasts (P

Protein-lipid composite nanoparticles featuring three-layer structure (protein layer, α-tocopherol layer and phospholipid layer) and an inner aqueous compartment have been developed recently as a delivery system for hydrophilic nutraceuticals. These composite nanoparticles overcome many shortfalls of sole protein or lipid nanoparticles, however, exhibited poor stability during storage and high burst release in the intestinal environment. In this study, the performance of these nanoparticles was improved by modifying the protein outer layer through succinylation. The increased surface charge and spatial extension of succinate chain on nanoparticle surface improved the nanoparticle stability in both physiological buffer and water. The crosslinking by succinate minimized the leakage of vitamin B12 to 4.5% during one month of storage. Moreover, succinylation slowed down pancreatic digestion of the protein shell, leading to a sustainable release within 10 h in the simulated intestinal fluid. Also, the modified nanoparticle increased the uptake efficiency of vitamin B12 over 20 folds and demonstrated a good mucoadhesive capacity. The in vivo efficacy study showed that the modified nanoparticle could correct a vitamin B12 deficiency in a rat model more efficiently than a free vitamin B12 supplement.

Ovonic threshold switching (OTS) selector is a key technology for high-density crossbar memory array. The basic characteristics of GeSe OTS material including structural information, film properties, microscopic properties, and electrical threshold switching behaviors are investigated by combining ab-initio molecular dynamics and experiments. Amorphous GeSe contains numerous Ge Se covalent bonds and defective structure motifs. The original resistance is extremely high compared to phase change materials, leading to lower leakage currents in device cells. The structure of GeSe remains stable at ∼350 °C and transforms to orthorhombic phase at higher temperature up to 450 °C. The severe phase separation of 500°C-annealed GeSe is observed with Se crystal grains. The high threshold voltage (>4 V) and holding voltage (>1 V) with large fluctuation (>1 V) are presented in the OTS cells with GeSe material. Due to the comprehensive investigations of GeSe material, we can improve the thermal stability and device performance of GeSe as a base material to find promising candidates for crossbar memory.

Purpose: How the neddylation pathway functions in breast tumor and regulation of estrogen receptor (ER) expression is rarely reported. The purpose of this study was to identify the role of neddylation in breast cancer and ER expression, and further explore the underlying mechanisms. Experimental Design: Expression patterns of nedd8-activating enzyme (NAE) and nedd8, two key proteins in the neddylation pathway, were examined in human breast specimens. ER-α expression was investigated using animal 18F-FES-PET/CT and immunoblotting upon NAE inhibitor MLN4924 treatment. Chromatin immunoprecipitation assay, luciferase reporter promoter assay, and the CRISPR-Cas9 system were used to elucidate the mechanism of ER-α regulation by MLN4924. The ER-positive breast cancer mouse model was used to determine the synergetic effect of MLN4924 and fulvestrant on tumor growth. All statistical tests were two-sided. Results: Both NAE1 and nedd8 expressions were higher in the ER-positive subgroup. Higher expressions of NAE1 and nedd8 indicated poorer prognosis. Importantly, ER-α expression was significantly downregulated upon MLN4924 treatment in vitro and in vivo. Mechanistically, MLN4924 treatment delayed serum and glucocorticoid-induced protein kinase (SGK) degradation and induced Forkhead box O3a (FOXO3a) nuclear export as well as decreased binding to the ESR1 promoter. Importantly, MLN4924 single or synergized with fulvestrant significantly suppressed the growth of ER-positive breast cancer in vitro and in vivo. Conclusions: Our proof-of-principle study determines the activation of neddylation in breast tumor tissues for the first time and reveals a new ER-α regulatory mechanism, as well as further explores an effective approach to improve fulvestrant sensitivity through a neddylation inactivation combination.

The objective of this study was to examine the diagnostic accuracy of sonographically guided core needle biopsy (CNB) of breast lesions in men. This was a retrospective study where we analyzed consecutive sonographically guided 14-gauge CNB results on 234 male breast lesions. The CNB accuracy is determined by the comparison between the CNB and its corresponding excisional biopsy or to long-term follow-up imaging. Sonographically guided CNB was effective to collect satisfactory samples from all 234 lesions. Out of those, 58.55% (137/234) were benign, 38.0% (89/234) were malignant, 1.71% (4/234) were papilloma with atypia and 1.71% (4/234) were atypical ductal hyperplasia lesions. Underestimation occurred in 3.4% (8/234) of the lesions. As for the detection of breast malignancy, the sensitivity of the CNB is 98.9%, specificity is 100%, negative predictive value is 99.3%, positive predictive value is 100%, false positive is 0% and false negative is 1.1%. The overall accuracy of sonographically guided CNB as a diagnostic tool is 99.6%. Sonographically guided 14-gauge CNB is an accurate, reliable and low invasive procedure for assessing breast lesions in men. Triple tests and follow-up checks of benign cases are essential for a successful breast biopsy program in men.

Phase change materials along the GeTe-Sb isoelectronic tie line are proved to be promising host material for optimization, based on which the well-known golden composition is developed. Here, Sc doped Ge2Sb1Te2 has been proposed for phase change memory (PCM) application, showing higher thermal stability and faster operation speed than those of the golden composition. The fast speed of 40 ns, high 10-year data retention of 160 °C, and good endurance of 6×105 cycles have made Sc0.2Ge2Sb1Te2 a promising candidate for PCM application. The impact of Sc on the microstructure is believed to be essential for those improvements in PCM.

How to distinguish exact working conditions is an open topic for a real world solar power station operated under unclear conditions and environmental variations. It is obvious that abnormal working conditions are rarely known beforehand. We hypothesize that currents and voltages of the solar power system could yield some statistical clusters that have certain physical implications. Without any prior knowledge on operation conditions, time series data of currents and voltages are divided into many subsequences to measure the similarities among subsequences through a dynamic time warping method, and then the similarities are classified through the k-means method. Meanwhile, the clusters yielded by the k-means method alone are used for comparison. Both approaches are evaluated by two external measures which suggest four clusters being the best number of clusters. To acquire real world data, a small test facility that is a scale-down version of a solar power station is built and operated under four working conditions such as normal working, partial shading, overall shading and open circuit fault. The experimental results show that four clusters of the unlabeled raw data are related to actual unknown working conditions where the accuracy of the coincidence rates is within 60–100%. It is also observed that the electrical faults are easily distinguished from other conditions with irradiation and temperature variations. The discovery to physical implication of time series clusters is important to develop advanced forecasting and fault diagnosis technologies in the field of photovoltaic power systems.

The leukocyte common antigen CD45 is a transmembrane phosphatase expressed on all nucleated hemopoietic cells, and the expression levels of its splicing isoforms are closely related to the development and function of lymphocytes. PEBP1P3 is a natural antisense transcript from the opposite strand of CD45 intron 2 and is predicted to be a noncoding RNA. The genotype-tissue expression and quantitative PCR data suggested that PEBP1P3 might be involved in the regulation of expression of CD45 splicing isoforms. To explore the regulatory mechanism of PEBP1P3 in CD45 expression, DNA methylation and histone modification were detected by bisulfate sequencing PCR and chromatin immunoprecipitation assays, respectively. The results showed that after the antisense RNA PEBP1P3 was knocked down by RNA interference, the DNA methylation of CD45 intron 2 was decreased and histone H3K9 and H3K36 trimethylation at the alternative splicing exons of CD45 DNA was increased. Knockdown of PEBP1P3 also increased the binding levels of chromatin conformation organizer CTCF at intron 2 and the alternative splicing exons of CD45. The present results indicate that the natural antisense RNA PEBP1P3 regulated the alternative splicing of CD45 RNA, and that might be correlated with the regulation of histone modification and DNA methylation.