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The recent past has witnessed remarkable progress in organic electronics, driven by the quest for flexible, lightweight, and cost-effective electronic devices. Semiconducting polymers (SCPs) have emerged as key materials in this field, offering unique electronic and optoelectronic properties along with mechanical flexibility. This study focuses on designing, synthesizing, and utilizing novel donor–acceptor (D–A) copolymer-based SCPs introducing a difluorothiophene moiety in the polymeric backbone. The importance of fluorine substitution for backbone planarity was verified by density functional theory calculations, comparing it with a nonfluorine substituted counterpart. Through the Unidirectional Floating Film Transfer Method (UFTM), we fabricated highly oriented thin films, resulting in increased optical anisotropy with dichroic ratios reaching 19.3 in PC20-FT thin films, one of the highest optical anisotropy observed for solution processable SCP thin films. X-ray diffraction and atomic force microscopy results validated the increase in the crystallinity and domain size with the increasing alkyl chain length. Finally, we elucidate these findings in the context of electrical applications by fabricating organic field-effect transistors revealing anisotropic charge transport achieving a promising mobility of 1.24 cm2V–1s–1and mobility anisotropy of 39.5. This study offers insights into the design principles and performance optimization of SCP-based devices, paving the way for advancements in plastic electronics.

Enzyme biofuel fuel cell (EBFC) is a green energy device that converts biological energy into electric energy effectively through the interaction of an enzyme and substrate. However, a low electron transfer (ET) rate and enzyme activity affect the performance of EBFC. Herein, we successfully encapsulated glucose oxidase (GOx) in zeolitic imidazolate framework-67 (ZIF-67) to form ZIF-67@GOx. Compared with ZIF-67-GOx based on the adsorption method, the embedding method not only increased the GOx load but also protected the GOx from environmental damage and improved the heat resistance and recyclability of the GOx. Furthermore, ZIF-67@GOx was combined with carbon nanotube (CNT) to construct an enzyme electrode based on GCE. The electrochemical performance of as-synthesized CNT/ZIF-67@GOx was analyzed by cyclic voltammetry (CV), electrochemical impedance spectroscopy, and linear sweep voltammetry. The proportions of CNT and ZIF-67@GOx of 1:5 obtained the optimal electrochemical performance. The ET constant (Ks) of the CNT/ZIF-67@GOx reached 6.2 s–1, which is 2.6 times that of CNT/ZIF-67-GOx. This proposed strategy based on the ZIF-6 material embedding will facilitate the construction of efficient enzyme electrodes.

Background and Objectives 4-Methylumbelliferone (4-MU) is a coumarin compound that can be extracted from the medicinal plant with anti-cancer properties, Smilax chinaL. In recent years, studies have revealed its potential as an anti-tumor and anti-metastasis drug with promising effects in cancer treatment. Despite an increase in research on the metabolic patterns of tumor cells, no prior research has suggested that 4-MU inhibits tumor proliferation by blocking glycolysis. This thesis presents evidence that 4-MU binds to proteins involved in glycolysis, thus mediating its anti-tumor effects.Materials and Methods Network pharmacology, transcriptomics, and molecular docking were utilized to forecast the potential targets and probable pathways of 4-MU’s anti-cancer activity, and the affinity of 4-MU towards potential targets was discovered using microscale thermophoresis (MST) detection.Results The results of transcriptome analysis brought to light that the genes with differential expressions were primarily enriched in metabolic pathways, including glycolysis-related proteins. Using network pharmacology and molecular docking, our study identified Heat Shock Protein 90 Alpha Family Class A Member 1 (Hsp90AA1), mitochondria, phosphoglycerate kinase 2 (PGK2), glycerol-3-phosphate dehydrogenase (GPD2), and glucose-6-phosphate isomerase (GPI) as potential targets of 4-MU. The strong binding affinity between 4-MU and these proteins was confirmed by the MST assay.Conclusion The findings indicate that 4-MU can hinder glycolysis by binding to glycolysis-associated proteins such as Hsp90AA1, PGK2, GPD2, and GPI. This results in the prevention of the energy supply to the tumor tissue, which ultimately curbs tumor growth, thereby demonstrating its anti-tumor properties. These results conclude that 4-MU has the capacity to be a novel glycolysis inhibitor for cancer treatment. Moreover, the identification of these glycolysis-associated proteins as possible targets for cancer therapy offers new avenues for research in the field of cancer treatment, thus providing further valuable evidence for the anti-cancer mechanism of 4-MU.

Perovskite tandem solar cells have met attractive concentrations with the potential to break through the Shockley–Queisser limit in single-junction photovoltaics. However, the efficiency of all-perovskite tandem solar cells is still challenging due to the deficiency of low-bandgap Pb–Sn mixed perovskite solar cells. In this work, high-performance hole-transporting layer free (HTL-free) low-bandgap perovskite (1.29 eV) tandem solar cells are simulated with 1-D solar cell capacitance simulator. By optimizing work function, thickness, and doping concentration of the perovskite layer, the power conversion efficiency (PCE) of HTL-free perovskite device reached to 19.14%. Furthermore, the all-perovskite tandem solar cell combined this HTL-free solar cell with MAGeI3 (1.9 eV) top solar is studied and the current matching condition between two subcells is obtained by the optimum thicknesses of perovskite layers, which are 700 and 350 nm for the bottom and top absorbers, respectively. The all-perovskite tandem solar cell reaches a PCE of 29.1%, which is among one of the top efficiency in perovskite-based solar cells.

Recently, deep learning has made brilliant achievements in wind turbine bearing fault diagnosis field. However, there are two problems that cannot be ignored: 1) the fault data are so scarce that it is time-consuming to acquire a well-behaved deep learning model and 2) much unlabeled data cannot be adequately utilized to explore useful fault information without prior. Therefore, a novel semi-supervised temporal meta-learning (SSTML) method is proposed, which can not only probe representative deep features from massive raw unlabeled vibration data adequately but also make the best of small annotation data to complete fault identification tasks. Transplanting meta-learning ideas into semi-supervised learning (SSL), a novel deep learning framework—SeMeF—is proposed. The proposed SeMeF is capable of drawing on the advantages of two mechanisms to exert efficiency beyond themselves. Furthermore, a temporal convolutional module is proposed to relieve overfitting due to the depth of the model, which can fully excavate temporal features along the depth of the network. The superiority of the proposed method is demonstrated on the wind turbine bearing dataset. Experimental results indicate that the model proposed can reach high diagnostic accuracy with limited annotation data, which outperforms many advanced deep learning models.

Decrypting the dynamics of receptor dimerization on cell membranes bears great importance in identifying the mechanisms regulating diverse cellular activities. In this regard, long-term monitoring of single-molecule behavior during receptor dimerization allows deepening insight into the dimerization process and tracking of the behavior of individual receptors, yet this remains to be realized. Herein, real-time observation of the receptor tyrosine kinases family (RTKs) at single-molecule level based on plasmon rulers was achieved for the first time, which enabled precise regulation and dynamic monitoring of the dimerization process by DNA programming with excellent photostability. Additionally, those nanoprobes demonstrated substantial application in the regulation of RTKs protein dimerization/phosphorylation and activation of downstream signaling pathways. The proposed nanoprobes hold considerable potential for elucidating the molecular mechanisms of single-receptor dimerization as well as the conformational transitions upon dimerization, providing a new paradigm for the precise manipulation and monitoring of specific single-receptor crosslink events in biological systems.

ObjectiveLong diagnostic delay remains an unsolved problem in many autoimmune rheumatic diseases (ARDs). One of the major contributing factors is poor symptom appraisal and the resulting delays in help-seeking by patients themselves. We therefore aimed to understand the symptom appraisal and help-seeking experience among patients with ARDs in a multiethnic urban Asian population and to explore its influencing factors.MethodsSemistructured interviews with 33 patients with ARDs were audio recorded and transcribed verbatim. We coded the transcripts deductively using the reported 3 stages of symptom appraisal (detection, interpretation, and response) as the framework, and inductively for newly emerging themes and subthemes.ResultsAll 3 stages of the symptom appraisal and help-seeking journey (ie, symptom detection [by self and by others], symptom interpretation [causes, consequences, and required actions] and symptom response [no action, self-management, seeking help from nonhealthcare professionals, and seeking help from healthcare professionals]) were observed among patients. Interactions among these 3 stages were also observed: symptom interpretation was found to influence subsequent symptom detection, and the outcome of symptom response was found to influence both subsequent symptom detection and symptom interpretation. Various personal and socioenvironmental factors (eg, knowledge and cultural beliefs about the symptom) that influenced symptom appraisal and help-seeking were identified from the interviews.ConclusionThe symptom appraisal and help-seeking journey of patients with ARDs is an iterative process of detection, interpretation, and response, and is influenced by various personal and socioenvironmental factors. Addressing modifiable factors could shorten the symptom appraisal and help-seeking interval and improve patient outcomes.

The nucleus is considered the most important organelle in the cell as it plays a central role in controlling cell reproduction, metabolism, and the cell cycle. The successful delivery of drugs into the nucleus can achieve excellent therapeutic effects, which reveals the potential of nucleus-targeted therapy in precision medicine. However, the transportation of therapeutics into the nucleus remains a significant challenge due to various biological barriers. Herein, we summarize the recent progress in the nucleus-targeted drug delivery system (NDDS). The structures of the nucleus and nuclear envelope are first described in order to understand the mechanisms by which drugs cross the nuclear envelope. Then, various drug delivery strategies based on the mechanisms and their applications are discussed. Finally, the challenges and solutions in the field of nucleus-targeted drug delivery are raised for developing a more efficient NDDS and promoting its clinical transformation.

Photo-Fenton catalytic oxidation is considered economical and eco-friendly technology for energy development and environmental protection. However, high-performance catalysts are vital in this process. Thus, in this study, an Fe-doped porous g-C3N4(Fe/PCN) nanomaterial was prepared viaa one-step self-assembly strategy, which showed a large specific surface area, relatively negative conduction potential and intense visible light utilization, exhibiting an enhanced catalytic performance. As expected, in the photo-Fenton catalytic system, 99.24% oxytetracycline (OTC) degraded over Fe/PCN within 60 min, and the photo-Fenton degradation rate constant was up to 0.076 min−1. Furthermore, a thimbleful of hydrogen peroxide (H2O2) could meet the requirement in this photo-Fenton reaction system. The catalytic mechanism of Fe/PCN was discussed in depth, where Fe/PCN not only activated H2O2to generate hydroxyl radicals (OH), but also photo-generated superoxide radicals (O2−) due to its more negative conduction potential (−0.78 eV vs.NHE) than E0(O2/O2−) (−0.33 eV vs.NHE). Besides, the stability experiment showed that the precipitation of iron salts was prevented, which is conductive for practical applications. The possible degradation pathway of OTC was proposed and proven to be green according to the toxicity estimation software tool (TEST). The low consumption of H2O2, high tolerance to pH changes and coexisting ions and green degradation pathway of the prepared Fe/PCN make it a potential candidate for OTC removal. This work proposes a simple method to modulate the morphology and structure of g-C3N4to enhance the catalytic activity of Fenton-like reactions.

Due to the complex working conditions, it is difficult to accurately extract the periodic pulse component of the rolling bearing vibration signal. The Ramanujan subspace (RS) theory has a good ability to extract periodic components (PCs). However, the theory divides signals by fixed period length, which means that the effect of extracting quasi-periodic signals is poor. Therefore, this article proposes an optimized periodic mode decomposition (OPMD) method to improve the defect and apply it to bearing fault diagnosis. First, the window length of the intercepted data segment is determined by periodicity measurement. Then, the pulse phase corresponding to each data segment is detected by correlation to divide the data segment, and cubic spline interpolation is used for phase compensation. Finally, the periodic pulse is extracted from the reconstructed signal. Simulation and experimental results show that compared with the existing RS methods, OPMD can extract better periodic pulses, reduce the impact of quasi-periodic signals on the extraction effect, and improve the adaptability of the algorithm.

Background: The utility of nailfold capillaroscopy in the evaluation of patients without Raynaud’s phenomenon is unclear.Objective: This study aims to compare the utility of nailfold capillaroscopy for the early diagnosis of the scleroderma-spectrum of diseases in patients who present with Raynaud’s phenomenon, undifferentiated non-Raynaud’s phenomenon features and positive systemic sclerosis-associated antibodies without scleroderma-spectrum of disease features.Methods: Eligible patients were divided into three referral criteria groups: (I) Raynaud’s phenomenon; (II) Undifferentiated non-Raynaud’s phenomenon features and (III) Positive systemic sclerosis-associated autoantibodies without features to suggest scleroderma-spectrum of diseases. This includes systemic sclerosis, mixed connective tissue disease and dermatomyositis. The association between baseline scleroderma pattern on nailfold capillaroscopy (systemic sclerosis–nailfold capillaroscopy) and final diagnosis at follow-up was determined using logistic regression analysis. Test characteristics of nailfold capillaroscopy were compared and stratified by referral groups.Results: Of 95 patients followed-up for a mean of 1.6 years, 28 (29.5%) patients developed scleroderma-spectrum of diseases, 36 (37.9%) patients had suspected/other connective tissue disease and 27 (28.4%) patients had no connective tissue disease. Baseline systemic sclerosis-nailfold capillaroscopy was significantly associated with the development of scleroderma-spectrum of diseases in patients from Group I (odds ratio, 7.1, p= 0.01) and Group II (odds ratio 7.3, p= 0.005). In Group II patients, nailfold capillaroscopy had a sensitivity, specificity, positive and negative predictive values of 71.4%, 76.5%, 55.6% and 86.7%, respectively. Specificity (81.8%) and PPV (69.2%) were the highest in Group I patients. Nailfold capillaroscopy had the highest negative predictive value in Group III (100%), followed by Group II (86.7%) and Group I (78.3%) patients.Conclusion: In addition to evaluating patients with Raynaud’s phenomenon, nailfold capillaroscopy was useful in the evaluation and exclusion of scleroderma-spectrum of diseases in patients with undifferentiated non-Raynaud phenomenon features and those with systemic sclerosis-associated antibodies without features to suggest scleroderma-spectrum of diseases.

To assess work productivity, identify associated factors and evaluate the economic burden of systemic sclerosis (SSc) in a multiethnic Asian population. Data on employment status and work productivity loss were collected. Associations between demographic and disease characteristics and unemployment status, work productivity loss, and activity impairment were examined using logistic and linear regression analyses, as appropriate. Costs of unemployment and work productivity loss were estimated using the human capital approach. Of 111 patients with a mean disease duration of 9.1 years, 33 (29.7%) were unemployed. Their mean age at unemployment was 44.2 years, equating to 22.8 years of lost employment. No demographic and disease characteristics were significantly associated with unemployment status in multivariable analysis. Of 73 employed patients, 39 (53.4%) reported work productivity loss, accounting for 45.9% of the working week. The presence of hyperlipidemia (coefficient –19.01, P= 0.03) was associated with work productivity loss in multivariable analysis. In total, 37 of 78 employed patients (47.4%) and 19 of 33 unemployed patients (57.6%) reported activity impairment, accounting for 42.2% and 50.0%, respectively, of the preceding week. The presence of hyperlipidemia (coefficient –18.56, P< 0.01) was associated with activity impairment in multivariable analysis. Annual cost of unemployment and work productivity loss were estimated to be $53,244 and $13,045 (Singapore dollar) per patient, respectively. SSc imposes significant unemployment and work productivity loss and causes a substantial economic burden to both affected individuals and society. Modifying the identified factors associated with unemployment and work productivity loss may reduce the burden of SSc.

Objectives: To delineate the disease-causing mutations of the Stargardt disease-related genes in Chinese patients diagnosed with Stargardt disease or retinitis pigmentosa (RP) by whole exome sequencing analysis. Methods: A total of 123 sporadic RP or Stargardt disease patients and 2 Stargardt disease families were recruited. All sporadic patients and the probands of the families were subjected to whole exome sequencing analysis. The candidate mutations were verified by direct sequencing based on the cosegregation pattern and in 200 control subjects and by the bioinformatics analyses. Results: A total of three reported ABCA4mutations were identified in the probands of the two Stargardt disease families. The probands and the affected family members with either homozygous or compound heterozygous mutations showed typical Stargardt disease features, which was absent in their unaffected family members. The cosegregation pattern confirmed the mode of recessive inheritance. Moreover, two sporadic Stargardt disease patients were identified to carry two novel ABCA4and one PROM1mutations. In addition, 13 novel variants were found in 119 sporadic RP patients in 7 Stargardt disease-related genes, and 8 novel missense variants were conserved across different species and predicted to be damaging to the protein. All 15 novel variants were absent in our 200 control subjects. Conclusions: This study revealed 22.4% study subjects carrying Stargardt disease-related gene mutations with total 15 novel variants in seven Stargardt disease-related genes, assuring that targeted next-generation sequencing analysis is a high throughput strategy to facilitate the clinical diagnosis from suspicious patients and recommended as a routine examination for inherited retinal dystrophies.

Inappropriate tillage practices and nitrogen (N) management have become seriously limitations for maize (Zea maysL.) yield and N use efficiency (NUE) in the North China Plain (NCP). In the current study, we examined the effects of strip deep rotary tillage (ST) combined with controlled-release (CR) urea on maize yield and NUE, and determined the physiological factors involved in yield formation and N accumulation during a 2-year field experiment. Compared with conventional rotary tillage (RT) and no-tillage (NT), ST increased the soil water content and soil mineral N content (Nmin) in the 20–40 cm soil layer due to reduction by 10.5 and 13.7% in the soil bulk density in the 0–40 cm soil layer, respectively. Compared with the values obtained by common urea (CU) fertilization, CR increased the Nminin the 0–40 cm soil layers by 12.4 and 10.3% at the silking and maturity stages, respectively. As a result, root length and total N accumulation were enhanced under ST and CR urea, which promoted greater leaf area and dry matter (particularly at post-silking), eventually increasing the 1 000-kernel weight of maize. Thus, ST increased the maize yield by 8.3 and 11.0% compared with RT and NT, respectively, whereas CR urea increased maize yield by 8.9% above the values obtained under CU. Because of greater grain yield and N accumulation, ST combined with CR urea improved the NUE substantially. These results show that ST coupled with CR urea is an effective practice to further increase maize yield and NUE by improving soil properties and N supply, so it should be considered for sustainable maize production in the NCP (and other similar areas worldwide).

P-Aminophenol (PAP), a potentially toxic and mutagenic compound, is widely distributed in water and soil and has serious side effects on human health. This study presents a convenient, sensitive, and effective dual-signal assay for the detection of PAP in the environment. Two-dimensional manganese dioxide (MnO2) nanosheets were used as the carrier and quencher for fluorophore-labelled DNA to form a dual-signal nanoprobe, MnO2–DNA. Based on a specific redox reaction between the MnO2nanosheets and target PAP, the corresponding absorption intensity of the product and the fluorescence intensity were both “turn-on” and also exhibited excellent correlation with the concentration of PAP. This strategy not only remarkably simplifies the detection process but also improves the reliability of results due to the dual-signal response, which has promising applications in environmental, clinical, and industrial research fields.

Kluyveromyces marxianusis expected to be used in the production of yeast extracts due to its good fermentation ability and nutritional properties. Yeast autolysis is a key process to produce yeast extract and vacuum negative pressure stress can be used as an effective way to assist autolysis. However, the molecular mechanism of initiating Kluyveromyces marxianusautolysis induced by vacuum negative pressure and the higher temperature is still unclear. In this study, RNA-seq technology was performed mainly to analyze autolytic processes in Kluyveromyces marxianusstrains. Considerable differentially expressed genes (DEGs) of downregulation were significantly enriched in 7 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to synthesis and transport of RNA and ribosome, which indicated that abnormal protein translations had already occurred in autolytic process. Interestingly, due to obvious change of related DEGs, endoplasmic reticulum-associated degradation (ERAD) and autophagy were activated and cell wall integrity pathway was hindered. Under the continuous influence of the external stress environment, the long-term changes of the above pathways triggered a vicious circle of gradual damage to yeast cells, which is the main cause of yeast autolysis. These results may provide important clues for the in-depth interpretation of the yeast autolytic mechanism.

Background: Conventional therapy may be inadequate for many patients with axial spondyloarthritis (axSpA). Traditional Chinese medicine (TCM) may be a viable alternative, but its effectiveness for axSpA is unknown. We are currently conducting a pragmatic randomised controlled trial (RCT) to investigate the effectiveness of a TCM collaborative model of care (TCMCMC), which combines usual rheumatologic care with acupuncture for patients with axSpA. This nested qualitative sub-study aims to identify facilitators of and barriers to the implementation of the TCMCMC.Methods: We conducted individual in-depth interviews with participants who had completed the acupuncture regimen to elicit opinions on the facilitators of and barriers to the implementation of the TCMCMC. The interviews were transcribed and analysed using thematic analysis.Results: Twelve participants were included, with data saturation occurring after 10 interviews. The analysis revealed both a number of important ‘facilitators’ and ‘barriers’. Facilitators to the implementation of the TCMCMC included effectiveness of TCM to relieve symptoms, inadequacy of conventional treatment and positive social perceptions of TCM. Barriers included scepticism towards TCM, inability of TCM to provide instant relief, needle-related discomfort, variable effectiveness of TCM influenced by physicians’ skills and experience and the high cost of TCM. Recommendations to overcome barriers included further patient education about TCM.Conclusion: Policymakers should take into account the various feasibility factors identified in this study when developing and implementing a TCMCMC.Trial registration number: NCT03420404 (ClinicalTrials.gov)

A simple process, rich information, and intelligent response are the goals pursued by cancer diagnosis and treatment. Herein, we developed a core–shell plasmonic nanomaterial (Au@MnO2-DNA), which consisted of a AuNP core with an outer shell MnO2nanosheet decorated with fluorophore modified DNA, to achieve the aforementioned aims. On the basis of the unique optical properties of plasmonic nanoparticles and the oxidability of the shell MnO2, scattering signal and fluorescence (FL) signal changes were both related to the expression level of glutathione (GSH), for which a dual-mode imaging analysis was successfully achieved on single optical microscope equipment with one-key switching. Meanwhile, the product of Mn2+from the reaction between MnO2and GSH not only served as a smart chemodynamic agent to initiate Fenton-like reaction for achieving chemodynamic therapy (CDT) of cancer cells but also relieved the side effect of intracellular GSH in cancer therapy. Therefore, the core–shell plasmonic nanomaterials with dual modal switching features and diagnostic properties act as excellent probes for achieving bioanalysis of aberrant levels of intracellular GSH and simultaneously activating the CDT of cancer cells based on the in situ reactions in cancer cells.

Chondroitin sulfate-mediated albumin corona nanoparticles were readily prepared without any chemical reaction, and their active tumor targeting and therapeutic effects were examined. Negatively charged chondroitin sulfate (CS) and positively charged doxorubicin (DOX) self-assembled into nanoparticles (CS-DOX-NPs) via electrostatic interactions. Bovine serum albumin (BSA) was then adsorbed on the surface of CS-DOX-NPs to form albumin corona nanoparticles (BC-DOX-NPs) protected from endogenous proteins. Due to the dual effect of BSA and CS, BC-DOX-NPs interacted with the gp60, SPARC and CD44 receptors on tumor cells, facilitating their rapid and efficient transcytosis and improving their accumulation and uptake within tumor tissues. The simultaneous presence of BSA and CS also allowed BC-DOX-NPs to target CD44 efficiently, leading to greater cellular uptake and cytotoxicity against 4T1 cells than CS-DOX-NPs or free DOX. Intravenous injection of BC-DOX-NPs into orthotopic 4T1 tumor-bearing mice led to greater drug accumulation at the tumor site than with CS-DOX-NPs or free DOX, resulting in significant inhibition of tumor growth and lower exposure of major organs to the drug.

The searching for new nonvolatile memories with the ability of working in harsh environments such as high temperature or humidity will be significant for industrial automation. Herein, a thermochromic polyoxometalate-based metal–organic framework (POMOF) constructed from Keggin-type polyoxometalates and metalloviologen has been fabricated as a nonvolatile memory device, which can exhibit stable nonvolatile memory behavior both at room and high temperature (150 °C) with stable cycle performance. Furthermore, its extreme working temperature can be monitored by color change from yellow to black, which stems from the reversible thermochromism of the POMOF. Importantly, the crystal structures at room and high temperature (150 °C) have been determined, which illustrates that the Keggin-type POM (α-GeW12O40)4–anions are anchored in the metalloviologen cationic [Co2(bpdo)4(H2O)6]n4n+cavities through numerous C–H···OPOMhydrogen bonds. The high temperature could not destroy its framework but remove its three lattice water molecules; in addition, more condensed structures with shorter Ge/W/Co–O lengths, stronger hydrogen bonds, and more distorted terminal bpdo ligands can be observed. Consequently, better cycling stability with a more uniform high-resistance state/low-resistance state can be achieved. Finally, the charge transport mechanism in this POMOF-based device during the resistive switching process has been discussed. In all, the combination of electron-poor metalloviologen with electron reservoir POM can give rise to the enhanced nonvolatile memory and better thermal stability accompanied with observable chromism.

ABSTRACTThe effects of polyaspartic acid and different controlled-release fertilizers with urea on dry matter accumulation and distribution, nitrogen absorption and accumulation, and the activities of enzymes involved nitrogen metabolism and yield of corn were studied by using xianyu (XY688), a maize nitrogen efficient cultivar, and Jifeng NO.2 (JF2), a maize nitrogen-inefficient cultivar, as experimental materials and through random blocks experimental design in 2019. For XY688, polyaspartic acid chelated nitrogen fertilizer (PASPN) had the highest yield, which was 21.34% higher than N0 treatment. For JF2, it also had the highest yield under PASPN combined urea treatment, which was 23.44% higher than N0 (no nitrogen fertilizer), and JF2 had a 9.7% lower yield under XY688 treatment. For XY688, PASPN treatment had the largest nitrogen uptake in grain, up to 3.14 kg/hm2, and PASPN treatment increased 17.4% compared with N0. For JF2, grain nitrogen uptake was also the highest under PASPN treatment, which was significantly different from other treatments. Nitrogen uptake was 3.16 kg/hm2, which increased 37.4% compared with N0. Compared with JF2, XY688 showed higher nitrogen uptake efficiency, nitrogen utilization efficiency, and partial nitrogen productivity. For XY688, the highest nitrogen absorption efficiency was SU3 (slow-release urea and ordinary urea) treatment (0.36 kg/kg). The partial nitrogen productivity and harvest index of PASPN treatment were the highest and significantly different from other treatments. The partial nitrogen productivity of PASPN treatment was 57.02 kg/kg. These results can provide help for the further researches of the rational utilization and absorption of nitrogen fertilizer.

Hsp90 is a potential therapeutic target for tumor, as it maintains the stability of a variety of proteins related to tumor development and progression. Autophagy is a self-degradation process to maintain cellular homeostasis and autophagy inhibitors can suppress tumor growth. In this study, we identified DCZ5248, a triazine derivative, was a dual inhibitor of both Hsp90 and late-autophagy with potent antitumor activity against colon cancer cells in vitro and in vivo. We showed that DCZ5248 (0.1–10 μM) induced dose-dependent degradation of Hsp90 client proteins (AKT, CDK4, CDK6 and RAF-1) in HCT 116 colon cancer cells through a proteasome-dependent pathway. Meanwhile, DCZ5248 (0.3 μM) induced cytoplasmic vacuole formation, LC3 II conversion, p62 protein upregulation, and inhibited autophagy at the late stage in the colon cancer cell lines tested. We further revealed that the inhibition of autophagy was achieved by impairing lysosomal functions through induction of lysosomal acidification and attenuation of lysosomal cathepsin activity. The modulation of autophagy by DCZ5248 was independent of Hsp90 inhibition as the autophagy inhibition was not blocked by Hsp90 knockdown. Importantly, inhibition of both Hsp90 function and autophagy by DCZ5248 induced G1-phase cell cycle arrest, apoptosis, and exerted potent antitumor activity against colon cancer cells both in vitro and in vivo. These findings demonstrate that DCZ5248 is a novel dual inhibitor of Hsp90 and autophagy with potential for colon cancer therapy.

To date, plasmon resonance energy transfer (PRET)-based analytical approaches still inevitably suffer from limitations, such as lack of appropriate acceptor–donor pairs and the extra requirements of active groups of acceptors, which place great obstacles in extending the application of such methods, especially in the area of living cell studies. Herein, we design and fabricate a kind of “loading-type” plasmonic nanomaterials constituting gold nanoparticles as donors of PRET coated with mesoporous silicon, in which organic small molecules (CHCN) as acceptors of PRET were loaded (Au@MSN-CHCN). This “loading-type” strategy could conveniently integrate acceptor–donor pairs into one nanoparticle, so as to achieve the goal of sensitive detection of biomolecules in a complex physiological microenvironment. Based on the change of PRET efficiency of Au@MSN-CHCN induced by the specific reaction between CHCN and peroxynitrite (ONOO–), ONOO–, which plays an irreplaceable role in a series of physiological and pathological processes, is sensitively and selectively detected. Furthermore, in situ imaging of exogenous and endogenous ONOO–in living cells was achieved even at a single nanoparticle level. This work provides a general approach to construct PRET probes for visualizing various biomolecules in living cells.

We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n= 22) vs. progression-free (n= 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n= 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565–6.628; p< 0.001), disease-free survival (DFS: HR 3.148, 95% CI 1.857–5.339; p< 0.001), and overall survival (OS: HR 3.790, 95% CI 2.237–6.423; p< 0.001) compared with low-risk patients. The prognostic accuracy of the classifier was validated in the internal testing (n= 84) and independent validation cohorts (n= 360). A prognostic nomogram consisting of five independent variables including the classifier, lactate dehydrogenase levels, ECOG-PS, central nervous system involvement, and NOTCH1/FBXW7status showed significantly greater prognostic accuracy than each single variable alone. The addition of a five-miRNA-based signature further enhanced the accuracy of this nomogram. Furthermore, patients with a nomogram score ≥154.2 significantly benefited from the BFM protocol. In conclusion, our nomogram comprising the 11-gene-based classifier may make contributions to individual prognosis prediction and treatment decision-making.

Purpose: To determine the expressions of SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2) genes in human and mouse ocular cells and comparison to other tissue cells. Methods: Human conjunctiva and primary pterygium tissues were collected from pterygium patients who underwent surgery. The expression of ACE2and TMPRSS2genes was determined in human primary conjunctival and pterygium cells, human ocular and other tissue cell lines, mesenchymal stem cells as well as mouse ocular and other tissues by reverse transcription-polymerase chain reaction (RT-PCR) and SYBR green PCR. Results: RT-PCR analysis showed consistent expression by 2 ACE2gene primers in 2 out of 3 human conjunctival cells and pterygium cell lines. Expression by 2 TMPRSS2gene primers could only be found in 1 out of 3 pterygium cell lines, but not in any conjunctival cells. Compared with the lung A549 cells, similar expression was noted in conjunctival and pterygium cells. In addition, mouse cornea had comparable expression of Tmprss2gene and lower but prominent Ace2 gene expression compared with the lung tissue. Conclusion: Considering the necessity of both ACE2 and TMPRSS2 for SARS-CoV-2 infection, our results suggest that conjunctiva would be less likely to be infected by SARS-CoV-2, whereas pterygium possesses some possibility of SARS-CoV-2 infection. With high and consistent expression of Ace2and Tmprss2in cornea, cornea rather than conjunctiva has higher potential to be infected by SARS-CoV-2. Precaution is necessary to prevent possible SARS-CoV-2 infection through ocular surface in clinical practice.

Metal-assisted deoxyribozyme catalysis (DNAzyme) has been a general platform for constructing highly sensitive and selective detection sensors of metal ions. However, the “always on” mode of the traditional DNAzyme sensors greatly limits their application in the visual analysis of endogenous metal ions in a complex physiological microenvironment. To overcome this obstacle, a smart acid-switchable DNAzyme nanodevice is designed to control the DNAzyme activity in living cells and achieve simultaneous visualization of metal ions (Zn2+and Pb2+) in situ. This nanodevice is built on DNAzyme precursors (DPs) and acid-switchable DNA (SW-DNA), precisely responding to pH variations in the range of 4.5–7.0, and the state of the three-strand hybridization of DPs successfully renders the DNAzymes inactive before being transported into cells. Once the nanodevice is taken up into living cells, the SW-DNA will change the configuration from linear to triplex in the acidic intracellular compartments (lysosomes, pH ∼4.5 to 5.0) and then the strands hybridized with the SW-DNA are liberated and subsequently react with DPs to form the active DNAzyme, which can further realize multi-imaging of intracellular metal ions. Moreover, this strategy has broad prospects as a powerful platform for constructing various acid-switchable nanodevices for visual analysis of multiple biomolecules in living cells.

Despite great achievements in sensitive and selective detection of important biomolecules in living cells, it is still challenging to develop smart and controllable sensing nanodevices for cellular studies that can be activated at desired time in target sites. To address this issue, we have constructed a remote-controlled “lock–unlock” nanosystem for visual analysis of endogenous potassium ions (K+), which employed a dual-stranded aptamer precursor (DSAP) as recognition molecules, SiO2based gold nanoshells (AuNS) as nanocarriers, and near-infrared ray (NIR) as the remotely applied stimulus. With the well-designed and activatable DSAP-AuNS, the deficiencies of traditional aptamer-based sensors have been successfully overcome, and the undesired response during transport has been avoided, especially in complex physiological microenvironments. While triggered by NIR, the increased local temperature of AuNS induced the dehybridiztion of DSAP, realized the “lock–unlock” switch of the DSAP-AuNS nanosystem, activated the binding capability of aptamer, and then monitored intracellular K+via the change of fluorescence signal. This DSAP-AuNS nanosystem not only allows us to visualize endogenous ions in living cells at a desired time but also paves the way for fabricating temporal controllable nanodevices for cellular studies.

Background: The risk factors for skin injuries remain poorly understood in cancer patients with peripherally inserted central catheters (PICC). We herein aimed at exploring the effect of clinical factors on the risk of PICC-related skin injuries.Methods: We included 1245 cancer patients with PICC from 16 hospitals in Suzhou, China. The study outcome was in-hospital skin injuries, including contact dermatitis, skin (epidermal) stripping, tension injury, allergic dermatitis, skin tear, maceration, folliculitis, and pressure injury.Results: During hospitalization, 274 patients (22.0%) developed skin injuries after prolonged use of an indwelling catheter. Univariable logistic regression analysis identified several risk factors for PICC-related skin injuries; multivariable logistic regression analysis showed that the following factors independently and significantly (p< 0.05) associated with the risk of PICC-related skin injuries: body mass index (BMI, >25 kg/m2versus <18.5 kg/m2: odds ratio (OR), 1.79; 95% confidence interval (CI), 1.03–3.11), skin condition (humid vs normal: OR, 2.96; 95% CI, 1.62–5.43), skin indentation (OR, 4.67; 95% CI, 3.31–6.58), allergic history (OR, 2.11; 95% CI, 1.21–3.66), history of dermatitis (OR, 3.05; 95% CI, 1.00–9.28), history of eczema (OR, 3.36; 95% CI, 1.20–9.43), catheter insertion site (under elbow vs. upper arm: OR, 3.32; 95% CI, 1.12–9.90), and PICC maintenance interval (4–5 days vs ⩽3 days: OR, 0.06; 95% CI, 0.01–0.50; 5–7 days vs ⩽3 days: OR, 0.07; 95% CI, 0.02–0.31; 7–9 days vs ⩽3 days: OR, 0.10; 95% CI, 0.02–0.57).Conclusions: BMI, skin condition, skin indentation, allergic history, history of dermatitis, history of eczema, catheter insertion site, and PICC maintenance interval were independent risk factors for PICC-related skin injuries in cancer patients. This knowledge will guide future studies with formulating optimal treatment strategies for improving the skin health of cancer patients with PICC.

Phosphatidic acid (PA) is a multifunctional lipid with important metabolic and signaling functions, and efforts to dissect its pleiotropy demand strategies for perturbing its levels with spatiotemporal precision. Previous membrane editing approaches for generating local PA pools used light-mediated induced proximity to recruit a PA-synthesizing enzyme, phospholipase D (PLD), from the cytosol to the target organelle membrane. Whereas these optogenetic PLDs exhibited high activity, their residual activity in the dark led to undesired chronic lipid production. Here, we report ultralow background membrane editors for PA wherein light directly controls PLD catalytic activity, as opposed to localization and access to substrates, exploiting a light–oxygen–voltage (LOV) domain-based conformational photoswitch inserted into the PLD sequence and enabling their stable and nonperturbative targeting to multiple organelle membranes. By coupling organelle-targeted LOVPLD activation to lipidomics analysis, we discovered different rates of metabolism for PA and its downstream products depending on the subcellular location of PA production. We also elucidated signaling roles for PA pools on different membranes in conferring local activation of AMP-activated protein kinase signaling. This work illustrates how membrane editors featuring acute, optogenetic conformational switches can provide new insights into organelle-selective lipid metabolic and signaling pathways.

Rolling element bearings are key components of mechanical equipment. The bearing fault characteristics are affected by the interaction in the vibration signals. The low harmonics of the bearing characteristic frequencies cannot be usually observed in the Fourier spectrum. The frequency loss in the bearing vibration signal is presented through two independent experiments in this paper. The existence of frequency loss phenomenon in the low frequencies, side band frequencies and resonant frequencies and revealed. It is demonstrated that the lost frequencies are actually suppressed by the internal action in the bearing fault signal rather than the external interference. The amplitude and distribution of the spectrum are changed due to the interaction of the bearing fault signal. The interaction mechanism of bearing fault signal is revealed through theoretical and practical analysis. Based on mathematical morphology, a new method is provided to recover the lost frequencies. The multi-resonant response signal of the defective bearing are decomposed into low frequency and high frequency response, and the lost frequencies are recovered by the combination morphological filter (CMF). The effectiveness of the proposed method is validated on simulated and experimental data.

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n= 75) and fetal thymus tissues (n= 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433–8.499, p< 0.001; overall survival (OS): HR 5.030, 95% CI 2.407–10.513, p< 0.001). This classifier displayed good performance in the internal testing set (n= 106) and the independent external set (n= 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127–2.488, p= 0.011; OS: HR 1.602, 95% CI 1.055–2.433, p= 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290–3.379, p= 0.003; OS: HR 1.996, 95% CI 1.203–3.311, p= 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.

Over-use of N fertilizer in crop production has resulted in a series of environmental problems in the North China Plain (NCP). Thus, improvement of nitrogen use efficiency (NUE) in summer maize has become an effective strategy for promoting sustainable agriculture in this region. Using twenty maize cultivars, plant dry matter production, N absorption and accumulation, yield formation, and NUE in summer maize were investigated under three N levels in two growing seasons. Based on their yield and yield components, these maize cultivars were categorized into four groups including efficient-efficient (EE) cultivars, high-nitrogen efficient (HNE) cultivars, low-nitrogen efficient (LNE) cultivars and nonefficient-nonefficient (NN) cultivars. In both two seasons, the EE cultivars improved grain yield together with increased plant biomass, and enhanced accumulative amounts as well as higher average grain yields than the other cultivar groups under deficient-N conditions. Significant correlations were observed between yield and kernel numbers (KN), dry matter (DM) amount and N accumulation at both post-silking and maturity stages. DM and N accumulation at late growth stage (i.e., from silking to maturity) contributed largely to the enhanced yield capacity and improved NUE under N-deficient conditions. Compared with the NN cultivars, the EE cultivars also showed increased N assimilation amount (NAA) and N remobilization content (NRC), and elevated N remobilization efficiency (NRE), NUE and nitrogen partial factor productivity (PFPN). Our investigation has revealed N-associated physiological processes and may provide guidance for cultivation and breeding of high yield and NUE summer maize under limited N conditions in the NCP.

Metal ion synergistically enhanced chemotherapy is a promising strategy for cancer treatment. However, targeting delivery of ions toward cancer cells remains challenging for decades. Herein, we developed a novel folic acid-nanogel (termed as FA-nanogel) with alkane chains as diffusion barriers for targeted transmembrane delivery of calcium ions into cancer cells. With the aid of hydrophobic diffusion barriers, the FA-nanogel showed a reduced and sustained speed for release of calcium ions, significantly prolonging the ion effect. Moreover, a pH-sensitive injectable hydrogel-loaded FA-nanogel and chemotherapeutic drug 5-fluorouracil (5-Fu) was synthesized for investigating the synergistic effect of nanogel on chemotherapy. Both in vitro and in vivo experiments confirmed that the intracellular calcium ions were continuously increased because of the targeted delivery ability and ion sustained release ability of the smart FA-nanogel, and the tumor growth was effectively inhibited by the ion synergistic chemotherapy. This study not only provides a powerful nanoplatform for sustained transmembrane delivery of ions into malignant cells but also creates better conditions for improving the therapeutic efficacy of chemotherapy.

BRAF and MEK inhibitors have shown remarkable clinical efficacy in BRAF-mutant melanoma; however, most patients develop resistance, which limits the clinical benefit of these agents. In this study, we found that the human melanoma cell clones, A375-DR and A375-TR, with acquired resistance to BRAF inhibitor dabrafenib and MEK inhibitor trametinib, were cross resistant to other MAPK pathway inhibitors. In these resistant cells, phosphorylation of ribosomal protein S6 (rpS6) but not phosphorylation of ERK or p90 ribosomal S6 kinase (RSK) were unable to be inhibited by MAPK pathway inhibitors. Notably, knockdown of rpS6 in these cells effectively downregulated G1phase-related proteins, including RB, cyclin D1, and CDK6, induced cell cycle arrest, and inhibited proliferation, suggesting that aberrant modulation of rpS6 phosphorylation contributed to the acquired resistance. Interestingly, RSK inhibitor had little effect on rpS6 phosphorylation and cell proliferation in resistant cells, whereas P70S6K inhibitor showed stronger inhibitory effects on rpS6 phosphorylation and cell proliferation in resistant cells than in parental cells. Thus regulation of rpS6 phosphorylation, which is predominantly mediated by BRAF/MEK/ERK/RSK signaling in parental cells, was switched to mTOR/P70S6K signaling in resistant cells. Furthermore, mTOR inhibitors alone overcame acquired resistance and rescued the sensitivity of the resistant cells when combined with BRAF/MEK inhibitors. Taken together, our findings indicate that RSK-independent phosphorylation of rpS6 confers resistance to MAPK pathway inhibitors in BRAF-mutant melanoma, and that mTOR inhibitor-based regimens may provide alternative strategies to overcome this acquired resistance.

Innovative techniques to measure microRNA (miRNA) in vivo could greatly improve the fundamental understanding of complex cellular processes. Herein, we report a novel method for real-time, quantitative miRNA detection inside living cells based on core–satellite plasmon rulers (PRs). This approach allows for the statistical analysis of single hybridization event caused by target miRNA. We investigated hundreds of satellite leaving events and found that the distribution of the time range for one strand displacement event is miRNA concentration-dependent, which obeyed Poisson statistics. Probing several such PRs under dark-field microscopy would provide precise determination of miRNA in vitro and in living cells, without photobleaching or blinking of the fluorophores. We believe the simple and practical approach on the basis of dynamic PRs with single-molecule sensitivity combined with statistical analysis hold promising potential to visualize native nucleic acids with short sequence and low-abundance.

The objective of this study was to investigate the effects of ultrasound‐guided injection of ultrasound contrast agents (UCAs) and the p53gene on the treatment of rats with breast cancer (BC). Assembly of the p53expression vector as well as that of a rat model with BC consisted of 200 successfully modeled rats randomly divided into 5 groups: p53gene introduction, p53gene introduction + ultrasound irradiation, p53gene introduction + UCAs, p53gene introduction + UCA + ultrasound irradiation, and UCA + ultrasound irradiation groups. Expression of p53was detected via quantitative real‐time polymerase chain reaction (qRT‐PCR), western blotting and immunohistochemical staining. In the p53gene introduction + ultrasound irradiation group, we observed increased tumor volume with blood flow signals around and necrotic tumor tissues with an inhibition rate of 36.30%, as well as higher expression of p53than that in the p53gene introduction group and p53gene introduction + UCA group. In the p53gene introduction + UCA + ultrasound irradiation group, tumor volume increased slightly with reduced blood flow signals and massive degenerative necrosis of tumor cells was identified with inhibition rate of 62.62%, and expression of p53was higher than that in the rest groups. Taken together, the key findings obtained from the present study elucidate that injection of p53gene and UCA microbubbles guided by ultrasound could increase the expression of p53, thus inhibiting the tumor growth in rats with BC.

The objective of this study was to investigate the effects of ultrasound-guided injection of ultrasound contrast agents (UCAs) and the p53gene on the treatment of rats with breast cancer (BC). Assembly of the p53expression vector as well as that of a rat model with BC consisted of 200 successfully modeled rats randomly divided into 5 groups: p53gene introduction, p53gene introduction + ultrasound irradiation, p53gene introduction + UCAs, p53gene introduction + UCA + ultrasound irradiation, and UCA + ultrasound irradiation groups. Expression of p53was detected via quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemical staining. In the p53gene introduction + ultrasound irradiation group, we observed increased tumor volume with blood flow signals around and necrotic tumor tissues with an inhibition rate of 36.30%, as well as higher expression of p53than that in the p53gene introduction group and p53gene introduction + UCA group. In the p53gene introduction + UCA + ultrasound irradiation group, tumor volume increased slightly with reduced blood flow signals and massive degenerative necrosis of tumor cells was identified with inhibition rate of 62.62%, and expression of p53was higher than that in the rest groups. Taken together, the key findings obtained from the present study elucidate that injection of p53gene and UCA microbubbles guided by ultrasound could increase the expression of p53, thus inhibiting the tumor growth in rats with BC.

Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health1. Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS)2–10. Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96–98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013–2016, predominantly in horseshoe bats (Rhinolophusspp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.

Lung cancer in never smokers (LCNS) has been considered as a separate disease and the 7thcause of cancer-related death worldwide. However, limited research has focused on “female” cohorts, which have presented a higher incidence rate. In this study, the microarray data of lung cancer tissues derived from 54 female lung cancer patients, consisting of 43 nonsmokers and 11 smokers, were selected from GSE2109 dataset. A total of 249 differentially expressed genes (DEGs) including 102 up- and 147 down-regulated genes were identified and further analyzed for gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment. By constructing protein–protein interaction (PPI) network and calculating key modules, 10 hub genes were screened out. The module analysis of the PPI network presented that the progression of female LCNS was significantly associated with immune response as chemokine activity and lipopolysaccharide response, and these biological processes (BP) might be mediated by chemokine signaling pathway and cytokine-cytokine receptor interaction. Then, survival analysis by Kaplan–Meier (K–M) Plotter online platform presented down-regulated gene colony stimulating factor 2 receptor beta common subunit (CSF2RB) of female LCNS might be involved in poor clinical outcome. Female LCNS with high expression of CSF2RB might be relevant with relative risk reduction of mortality, longer median survival time and higher 5-year survival rate, while female LCNS with low expression of CSF2RB might be implicated in a poor clinical outcome. In short, our results support CSF2RB to be a candidate survival predictor for female LCNS.

The high-density defect states existing at the grain boundaries and heterojunction interfaces induce nonradiative charge recombination and ion migration processes within perovskite film, which seriously impair the device efficiency and stability. Here, we propose a novel synergistic ion-anchoring passivation (SIP) strategy for high-performance perovskite solar cells, by designing a multifunctional molecule to heal the charged defects via electrostatic interactions. The anion and cation species of the multifunctional molecule are rationally screened via high-throughput DFT simulation and experimental verification, which act as efficient surface passivation agents to heal the lead- and iodine-related defects. As a result, the defect-less perovskite films deliver encouraging device power conversion efficiency >24% with negligible hysteresis. A remarkable open-circuit voltage (Voc) of 1.17 V was obtained with a Vocdeficit of 370 mV, featuring the outstanding defect-passivation capability of the SIP strategy. Moreover, the SIP-treated devices show exceptional ambient stability and maintain 70% of the initial efficiency after 150 h of high humidity exposure (relative humidity 70%–80%). Our results highlight the importance of the rational design of passivation agents to realize high-performance perovskite electronics.

Willed-movement training has been demonstrated to be a promising approach to increase motor performance and neural plasticity in ischemic rats. However, little is known regarding the molecular signals that are involved in neural plasticity following willed-movement training. To investigate the potential signals related to neural plasticity following willed-movement training, littermate rats were randomly assigned into three groups: middle cerebral artery occlusion, environmental modification, and willed-movement training. The infarct volume was measured 18 d after occlusion of the right middle cerebral artery. Reverse transcription-polymerase chain reaction (PCR) and immunofluorescence staining were used to detect the changes in the signal transducer and activator of transcription 3 (STAT3) mRNA and protein, respectively. A chromatin immunoprecipitation was used to investigate whether STAT3 bound to plasticity-related genes, such as brain-derived neurotrophic factor (BDNF), synaptophysin, and protein interacting with C kinase 1 (PICK1). In this study, we demonstrated that STAT3 mRNA and protein were markedly increased following 15-d willed-movement training in the ischemic hemispheres of the treated rats. STAT3 bound to BDNF, PICK1, and synaptophysin promoters in the neocortical cells of rats. These data suggest that the increased STAT3 levels after willed-movement training might play critical roles in the neural plasticity by directly regulating plasticity-related genes.

PLGA, poly (lactic-co-glycolic-acid), is a kind of biodegradable functional macromolecular organic compounds. PLGA, certified by the Food and Drug Administration (FDA), possesses desirable features of biocompatibility, nontoxicity and no immune response, and is being widely applied to human clinical medical research. Because of its biodegradability, simple synthetic methods, controllability of degrading rate and desirable plasticity, PLGA was applied in large quantity into the carrier materials which is to control the release in recent years, gradually propelling PLGA microsphere controlled release system to be the most ideal drug-carrier system at present. As the carrier of drug and genes, PLGA is mainly researched on its features as the carrier, synthetic methods, different surface modification methods, and the applications on different drugs, genetic treatments and genetic vaccines.

IMPORTANCE: Hypertension is a leading cause of premature death in China, but limited evidence is available on the prevalence and management of hypertension and its effect on mortality from cardiovascular disease (CVD). OBJECTIVES: To examine the prevalence, diagnosis, treatment, and control of hypertension and to assess the CVD mortality attributable to hypertension in China. DESIGN, SETTING AND PARTICIPANTS: This prospective cohort study (China Kadoorie Biobank Study) recruited 500 223 adults, aged 35 to 74 years, from the general population in China. Blood pressure (BP) measurements were recorded as part of the baseline survey from June 25, 2004, to August 5, 2009, and 7028 deaths due to CVD were recorded before January 1, 2014 (mean duration of follow-up: 7.2 years). Data were analyzed from June 9, 2014, to July 17, 2015. EXPOSURES: Prevalence and diagnosis of hypertension (systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or receiving treatment for hypertension) and treatment and control rates overall and in various population subgroups. MAIN OUTCOMES AND MEASURES: Cox regression analysis yielded age- and sex-specific rate ratios for deaths due to CVD comparing participants with and without uncontrolled hypertension, which were used to estimate the number of CVD deaths attributable to hypertension. RESULTS: The cohort included 205 167 men (41.0%) and 295 056 women (59.0%) with a mean (SD) age of 52 (10) years for both sexes. Overall, 32.5% of participants had hypertension; the prevalence increased with age (from 12.6% at 35-39 years of age to 58.4% at 70-74 years of age) and varied substantially by region (range, 22.7%-40.7%). Of those with hypertension, 30.5% had received a diagnosis from a physician; of those with a diagnosis of hypertension, 46.4% were being treated; and of those treated, 29.6% had their hypertension controlled (ie, systolic BP &lt;140 mm Hg; diastolic BP &lt;90 mm Hg), resulting in an overall control rate of 4.2%. Even among patients with hypertension and prior CVD, only 13.0% had their hypertension controlled. Uncontrolled hypertension was associated with relative risks for CVD mortality of 4.1 (95% CI, 3.7-4.6), 2.6 (95% CI, 2.4-2.9) and 1.9 (95% CI, 1.8-2.0) at ages 35 to 59, 60 to 69, and 70 to 79 years, respectively, and accounted for about one-third of deaths due to CVD (approximately 750 000) at 35 to 79 years of age in 2010. CONCLUSIONS AND RELEVANCE: About one-third of Chinese adults in this national cohort population had hypertension. The levels of diagnosis, treatment, and control were much lower than in Western populations, and were associated with significant excess mortality.

Respiratory pathogens transmit primarily through particles such as droplets and aerosols. Although often overlooked, the resuspension of settled droplets is also a key facilitator of disease transmission. In this review, we discuss the three main mechanisms of aerosol generation: direct generation such as coughing and sneezing, indirect generation such as medical procedures, and resuspension of settled droplets and aerosols. The size of particles and environmental factors influence their airborne lifetime and ability to cause infection. Specifically, humidity and temperature are key factors controlling the evaporation of suspended droplets, consequently affecting the duration in which particles remain airborne. We also suggest material‐based approaches for effective prevention of disease transmission. These approaches include electrostatically charged virucidal agents and surface coatings, which have been shown to be highly effective in deactivating and reducing resuspension of pathogen‐laden aerosols. Virus dissemination through droplets or aerosols is a predominant transmission mode of respiratory infections. This review summarizes direct and indirect mechanisms of aerosol generation with an emphasis on infection risks presented by the resuspension of settled droplets. Material‐based approaches, including nanotechnology, to contain bioaerosol‐mediated virus transmission are highlighted in this review.

Objective: To reveal the cutoff point and influencing factors in the dynamic change in phenotypic group in patients with stable angina pectoris (SAP) after Xinxuekang capsule treatment. Methods: Five hundred and seventy-six SAP patients were randomly assigned to receive Xinxuekang (XXK) capsules or Compound Danshen (CDS) tablets for 8 weeks. Global similarity degree analysis and nonlinear mixed effects modeling (NONMEM) were employed to reveal the cutoff points and influencing factors in dynamic changes in the SAP phenotypic group. The phenotypic group was defined as the six phenotypes in SAP, including angina, choking sensation in the chest, palpitations, dark purple lips, ecchymosis on the tongue, and fine-choppy pulse, which were quantitatively evaluated on Days 0, 14, 28, 42, and 56. Results: Variation in the six individual phenotypes and distribution of the SAP phenotypic profile were similar between the two experimental groups, but cutoff points for changes in the SAP phenotypic group were 7.28 and 10.73 weeks in XXK and CDS groups, respectively. Degree of severity of SAP as well as study site significantly affected the tendency for change in the SAP Xueyu Zheng in both XXK and CDS treatment groups. Different Chinese patent drugs affected the tendency for change in phenotypic group in patients with SAP. XXK was superior to CDS in controlling a clinical phenotypic group. Conclusion: Based on global similarity degree analysis and NONMEM, the cutoff point and influencing factors in phenomic variation of SAP may be determined, to improve the development and modification of treatment regimens.

Chitosan is a kind of natural polymer commonly applied for nanomaterials, which is affluent in nature with favorable biodegradability and biocompatibility and free of toxicity or odor. In clinic it can be used as a drug carrier for the treatment of cancer, and also it is a kind of new pharmaceutical excipient. To prepare chitosan nanomaterial, various method are used, such as ionic crosslinking, covalent crosslinking, precipitation, free radical polymerization, reverse micelle, spray drying, and self-assembly. Furthermore, plenty of anti-tumor drugs, including adriamycin, epirubicin, taxol, 5-fluorouracil, norcantharidin, folic acid, and so on, are also attempted to load on these chitosan nanocarriers. In addition, the mechanism for those nanocarriers carrying anti-tumor drugs acting on tumor cell were explored, and the formulation mainly include electric charge adhesion effect, suppressing the proliferation of tumor cells, adjusting or enhancing immune ability of the body and inducing apoptosis. This paper compared the characteristics of different preparation methods on chitosan as a nanodrug carrier, summarized the types of packaged drugs, analyzed the mechanism of the chitosan as nanodrug carriers. It can provide valuable reference for researchers' further work.