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Over the last two decades, in-person interviewing costs continued to increase while the data quality advantages traditionally identified with this data collection mode have faded. Consequently, some longitudinal surveys have begun transitioning from in-person to web data collection despite risks to data quality and longitudinal comparability. This paper addresses the major issues involved in the transition process and proposes a multi-sample, multi-phase responsive design that attempts to minimize the data quality risks while preserving the considerable cost savings promised by the transition. The paper describes the design as it was applied to the National Longitudinal Study of Adolescent to Adult Health (Add Health)—a nationally representative panel survey of around 20,000 adolescents selected from grades 7 to 12 (typically 13 to 18 years of age) in the 1994–95 school year. Also described are key results from several experiments embedded within the design and the analysis of mode effects. Also presented are some lessons learned and recommendations for other in-person panel surveys that may be contemplating a similar transition to web or mixed-mode data collection.

Rab22a-NeoF fusion protein has recently been reported as a promising target for osteosarcoma lung metastasis. However, how this fusion protein is regulated in cells remains unknown. Here, using multiple screenings, it is reported that Rab22a-NeoF1 fusion protein is degraded by an E3 ligase STUB1 via the autophagy receptor NDP52-mediated lysosome pathway, which is facilitated by PINK1 kinase. Mechanistically, STUB1 catalyzes the K63-linked ubiquitin chains on lysine112 of Rab22a-NeoF1, which is responsible for the binding of Rab22a-NeoF1 to NDP52, resulting in lysosomal degradation of Rab22a-NeoF1. PINK1 is able to phosphorylate Rab22a-NeoF1 at serine120, which promotes ubiquitination and degradation of Rab22a-NeoF1. Consistently, by upregulating PINK1, Sorafenib and Regorafenib can inhibit osteosarcoma lung metastasis induced by Rab22a-NeoF1. These findings reveal that the lysosomal degradation of Rab22a-NeoF1 fusion protein is targetable for osteosarcoma lung metastasis, proposing that Sorafenib and Regorafenib may benefit cancer patients who are positive for the RAB22A-NeoF1 fusion gene.

The existing research on the Internet of Vehicles (IoV) based on blockchain adopts the single chain mode. However, in the face of large-scale data environment, it is difficult to ensure the security and efficiency of large-scale data storage by using single chain. Thus, this paper is devoted to the research on the master-slave multi-chain IoV architecture. In the proposed architecture, there are two major innovations: 1) By defining three different data structures, micro-block, key-block and verification-block, the master-slave multi-chain model based on hash anchoring is designed to break through the data of the whole network. It ensures the consistency and integrity of IoV data, and solves the problem of privacy disclosure caused by insecure data storage; 2) A data upload and access mechanism based on attribute encryption is designed between users and RSU nodes. It solves the problem of privacy disclosure caused by insecure transmission outside the data chain. Finally, we verify that the proposed architecture is more suitable for large-scale data scenario by simulation analysis of system response time and encryption/decryption overhead.

Mental health literacy (MHL) is rarely reported in the Chinese elderly. This study explored the pattern of MHL in the Chinese elderly in relation to depression, anxiety and poor sleep quality.A cross-sectional study was conducted among older adults in Guangzhou, south China. Participants were investigated face-to-face using the Chinese National Mental Health Literacy Scale, the Patient Health Questionnaire-9 item (PHQ-9), the 7-item Generalized Anxiety Disorder (GAD-7) and the Pittsburgh Sleep Quality Index (PSQI). Mental Health Literacy Scale contains three dimensions: mental health knowledge, mental health skills (such as social support, cognitive reappraisal and attentional distraction) and mental health awareness. Multivariate logistic regression was used for examining the association between MHL and mental health.A total of 506 older adults were recruited. The percentage of depression, anxiety, and poor sleep quality were 16.6%, 7.9% and 40.9%, respectively. MHL dimensions independently associated with depression included cognitive reappraisal (OR = 1.95, p .001), attentional distraction (OR = 0.61, p = 0.044) and awareness (OR = 0.56, p = 0.027). MHL dimensions independently associated with anxiety symptoms included cognitive reappraisal (OR = 1.90, p = 0.011) and attentional distraction (OR = 0.44, p = 0.016). MHL dimensions independently associated with poor sleep quality included social support (OR = 0.75, p = 0.022), cognitive reappraisal (OR = 1.55, p = 0.003) and attentional distraction (OR = 0.65, p = 0.016).Given the low MHL and its association with poor mental health in the Chinese elderly, policymakers and health professionals should improve the older adults' MHL, which could be conducive to the prevention and control of their mental health problems.

Background Leukemogenesis is proposed to be a multistep process by which normal hematopoietic stem and progenitor cells are transformed into full-blown leukemic cells, the details of which are not fully understood. Methods We performed serial single-cell transcriptome analyses(10X genomics) of preleukemic and leukemic cells (PLCs) and constructed the cellular and molecular transformation trajectory in a Myc-driven AML model in mice, which represented the transformation course in patients. Another single-cell approach, Smart Seq2, was used to analyze alternative splicing events in leukemic cell. Results We found that the Myc targets were gradually upregulated along the trajectory. Among them were splicing factors, which showed stage-specific prognosis for AML patients. Furthermore, we dissected the detailed gene network of a tipping point for HSPCs to generate initiating PLCs, which was characterized by dramatically increased splicing factors and unusual RNA velocity. In the late stage, PLCs acquired explosive heterogeneity through RNA alternative splicing. Among them, the Hsp90aahi subpopulation was conserved in both human and mouse AML and associated with poor prognosis. Exon 6 skipping of Tmem134 was identified in these cells. While the exon skipping product Tmem134β promoted the cell cycle, full-length Tmem134α delayed tumorigenesis. Conclusion Our study emphasized the critical roles of RNA splicing in the full process of leukemogenesis and identified the role of a novel tumor specific alternative splicing event, Exon 6 skipping of Tmem134, during the occurrence and maintenance of leukemia.

Several clinical trials have investigated the effects of Melissa officinalis (lemon balm) on cardiovascular risk factors, but have yielded conflicting results and had only modest sample sizes. The aim of this pool analysis was to summarize the evidence of the effects of Melissa officinalis supplementation on plasma lipid profiles, body weight, blood pressure and glucose levels. Original randomized controlled trials (RCTs) that assessed the clinical effects of Melissa officinalis consumption in human participants and published before June 2020 were identified by searching online databases, including PubMed, Scopus, Web of Science and Google Scholar databases. The quality of trials was assessed using the Cochrane Risk of Bias Tool. Quantitative data analysis was performed using weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. Standard methods for assessing statistical heterogeneity and publication bias were used, respectively. Four trials with 244 participants were included in the final analysis. Pooling of results showed that Melissa officinalis significantly lowered total cholesterol (TC) (WMD, -7.55 mg/dL; 95% CI -14.99, -0.12; P=0.045), low-density lipoprotein cholesterol (LDL-C) (WMD, -11.33 mg/dL; 95% CI -19.46, -3.21; P=0.006), glycated hemoglobin (HbA1c) (WMD, -0.35 %; 95% CI -0.64, -0.07; P=0.01), and Systolic blood pressure (SBP) (WMD, -0.89 mmHg; 95% CI-1.69, -0.09; P=0.03). The use of Melissa officinalis did not appear to significantly alter any other study endpoints. The present findings showed that supplementation with Melissa officinalis extract were associated with a significant reduction in TC, LDL-C, HbA1c, and SBP in humans.

Understanding how soil phosphorus (P) fractions change is critical to achieve more efficient soil P use in a highly P-sorbing calcareous soil. The fields were managed without or with annual P fertilizer (40 kg P ha− 1), continuously growing sole cropping or intercropping of maize and faba bean. Soil samples (0–200 mm) were collected at the start of the experiment and eight years later, and we evaluated P fractions using sequential fractionation. Maize/faba bean intercropping had an average land equivalent ratio (LER) of 1.2, a similar P content as sole maize, while both acquired more P than sole faba bean. Compared with the original soil P fractions in 2009, three cropping systems, regardless of P fertilization, depleted the labile P pool (Resin-P and NaHCO3-Pi), while Residual-P and NaHCO3-Po accumulated. Eight years of no P input showed sole maize mainly depleted NaOH-Pi and conc. HCl-Pi, sole faba bean depleting NaOH-Po, while intercropping depleted the most abundant P fraction, 1 M HCl-Pi, in addition to NaOH-Pi. However, long-term P application caused the cropping systems to accumulate 1 M HCl-Pi while depleting the conc. HCl-Po fraction; both sole faba bean and intercropping showed accumulation of NaOH-Pi, while depleting NaOH-Po. Long-term appropriate P input enhanced the mineralization of mod-labile and non-labile organic P and accumulation of mod-labile inorganic P. Sole maize consistently depleted inorganic P and sole faba bean without P input depleted organic P, while intercropping accessed P pools varying with P input.

Guided, programmable, and target-activated nucleases, exemplified by Cas in the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) system and Argonaute (Ago), are emerging as a new generation of nucleic acid tests (NATs). A specific approach for comparison of these two nucleases side by side in terms of similarities, differences, and complementarities is instrumental for the sensible design of novel NATs.

To investigate the alterations of topological organization of the whole brain functional networks in hypertension patients with cognitive impairment (HTN-CI) and characterize its relationship with cognitive scores.Fifty-seven hypertension patients with cognitive impairment and 59 hypertension patients with normal cognition (HTN-NC), and 49 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Graph theoretical analysis was used to investigate the altered topological organization of the functional brain networks. The global topological properties and nodal metrics were compared among the three groups. Network-based statistic (NBS) analysis was used to determine the connected subnetwork. The relationships between network metrics and cognitive scores were also characterized.HTN-CI patients exhibited significantly decreased global efficiency, lambda, and increased shortest path length when compared with HCs. In addition, both HTN-CI and HTN-NC groups exhibited altered nodal degree centrality and nodal efficiency in the right precentral gyrus. The disruptions of global network metrics (lambda, Lp) and the nodal metrics (degree centrality and nodal efficiency) in the right precentral gyrus were positively correlated with the MoCA scores in HTN-CI. NBS analysis demonstrated that decreased subnetwork connectivity was present both in the HTN-CI and HTN-NC groups, which were mainly involved in the default mode network, frontoparietal network, and cingulo-opercular network.This study demonstrated the alterations of topographical organization and subnetwork connectivity of functional brain networks in HTN-CI. In addition, the global and nodal network properties were correlated with cognitive scores, which may provide useful insights for the understanding of neuropsychological mechanisms underlying HTN-CI.

It remains unknown for decades how some of the therapeutic fusion proteins positive in a small percentage of cancer cells account for patient outcome. Here, we report that osteosarcoma Rab22a-NeoF1 fusion protein, together with its binding partner PYK2, is sorted into exosomes by HSP90 via its KFERQ-like motif (RVLFLN142). The exosomal Rab22a-NeoF1 fusion protein facilitates the pulmonary pre-metastatic niche formation by recruiting bone marrow-derived macrophages. The exosomal PYK2 activates RhoA in its negative recipient osteosarcoma cells and induces signal transducer and activator of transcription 3 activation in its recipient macrophages to increase M2 phenotype. Consequently, lung metastases of its recipient osteosarcoma cells are promoted by this exosomal Rab22a-NeoF1 fusion protein, and this event can be targeted by disrupting its interaction with PYK2 using a designed internalizing RGD peptide.

Background Gastric cancer is the second leading cancer-related mortality worldwide and more effective treatment strategies are urgently needed to combat the disease. Using lipoteichoic acid (LTA) and miR-27b-3p agomir, we aimed to assess the efficacy of this combination of therapies in treating gastric cancer. Methods The RNA levels of miR-27b-3p, FOXO3, MET, KRAS, vascular endothelial growth factor C (VEGFC), TSC1, and P65 were analyzed by quantified-PCR (Q-PCR) and the cell viability of AGS cells was analyzed by MTT. Confirm Luciferase reporter assays were used to explore the putative miR-27b-3p binding sites and Western blot analyzed the protein level of GAPDH, VEGFC, P65, AKT, and phosphorylated-AKT (p-AKT). The level of P65 in both the cytoplasm and nucleus of AGS cells was visualized by immunofluorescence assay. Subcutaneous xenograft models of gastric cancer were established, and mice were treated with miR-27b-3p agomir, LTA, or both. Hematoxylin-eosin staining and Ki-67 immunohistochemistry analysis of tumor tissues were then performed. Results The results showed that the decreased expression of miR-27b-3p in gastric cancer cell lines inhibited the viability of AGS cells, and VEGFC was confirmed as the target of miR-27b-3p. In addition, ectopic expression of miR-27b-3p significantly inhibited the AKT pathway in AGS and N87 cells, and LTA suppressed the proliferation of gastric cancer cells by inhibiting the NF-κB pathway. In an established xenograft model, both miR-27b-3p agomir alone and LTA treatment alone inhibited tumor growth and treatment which combined the two showed an even stronger inhibitory effect. Conclusions Taken together, the combined use of LTA and miR-27b-3p agomir exhibited a synergistic effect in the treatment of gastric cancer.

Affective materials have always been an important factor in improving the efficiency of affect related research for their ecological validity. In order to achieve high ecological validity in emotion elicitation, this paper proposed a novel Affective Virtual Reality System (AVRS) by utilizing the immersion, privacy and design flexibility of virtual reality. Design elements including subject features, sound features, motion features and color features were extracted by referring to the referenced emotion materials, art works and the existing VR scenes. Affective VR scenes were then designed by Unreal Engine 4.12 and their effectiveness was validated by Self-Assessment Manikin (SAM). Furthermore, arousal was used as an indicator to compare the difference of ecological validity between VR and video emotional materials with an intergroup experiment through Electroencephalography (EEG), Heart Rate (HR), Galvanic Skin Response (GSR), and SAM. Results proved that VR scenes could achieve the same emotion elicitation as video. Especially, there was significant difference in measures of Fearful in SAM evaluation, indicating that VR emotion materials were expected to deliver a good effect on negative emotional scenes. The proposed AVRS as well as the multimodal physiological signal database with valence, arousal and dominance (VAD) labels could help the development of emotion related studies.

Constructing Z-scheme photocatalysts is one of the most effective technologies to enhance the photocatalytic reduction or oxidation ability in artificial photosynthesis. For the BiVO4 photocatalyst, it usually shows limited photocatalytic ability because of the severe bulk recombination of photogenerated carriers and the poor reduction reaction of photogenerated electrons. In this paper, a novel plasmonic Z-scheme Pt-Au/BiVO4 single-crystal photocatalyst was constructed to solve the above issues. Here, Au nanoparticles are selectively deposited on the electron-rich (0 1 0) facet of BiVO4, while Pt nanoparticles are selectively modified on the Au surface. Photocatalytic results indicated that the resultant Pt-Au/BiVO4 Z-scheme photocatalyst exhibits an obviously higher photocatalytic performance than pure BiVO4, Au/BiVO4, randomly deposited BiVO4(Pt-Au/BiVO4(R)) and conventional Pt-Au/BiVO4. More importantly, compared with the well-known Pt/BiVO4(2.0 wt%), the Pt-Au/BiVO4 not only exhibits a higher photocatalytic performance, but also loads a lower amount of high-cost Pt cocatalyst. The excellent photocatalytic activity of the plasmonic Z-scheme Pt-Au/BiVO4 photocatalyst can be attributed to the synergistic effect of crystal-facet engineering and selective loading of Pt-Au, which results in the orientation transfer of photogenerated carriers in the single-crystal BiVO4, the enhanced reduction power of photogenerated electrons, and the rapid oxygen-reduction reaction on Pt cocatalyst.

We use extrapolation acceleration technique to speed up the preconditioned square block matrix splitting iteration method for two-by-two block linear systems. It is shown that for relaxation parameter omega = 4/3, the convergence factor of the iteration method under consideration is 1/3. This yields the robustness and efficiency of the method. Numerical examples confirm the theoretical results and demonstrate the effectiveness of the approach developed.

Osteosarcoma is a type of aggressive malignant bone tumour that frequently metastasizes to lungs, resulting in poor prognosis. However, the molecular mechanisms of lung metastasis of osteosarcoma remain poorly understood. Here we identify exon-intron fusion genes in osteosarcoma cell lines and tissues. These fusion genes are derived from chromosomal translocations that juxtapose the coding region for amino acids 1-38 of Rab22a (Rab22a1-38) with multiple inverted introns and untranslated regions of chromosome 20. The resulting translation products, designated Rab22a-NeoFs, acquire the ability to drive lung metastasis of osteosarcoma. The Rab22a1-38 moiety governs the function of Rab22a-NeoFs by binding to SmgGDS-607, a GTP-GDP exchange factor of RhoA. This association facilitates the release of GTP-bound RhoA from SmgGDS-607, which induces increased activity of RhoA and promotes metastasis. Disrupting the interaction between Rab22a-NeoF1 and SmgGDS-607 with a synthetic peptide prevents lung metastasis in an orthotopic model of osteosarcoma. Our findings may provide a promising strategy for a subset of osteosarcoma patients with lung metastases.

In recent years, the rapid increase in the number and type of Android malware has brought great challenges and pressure to malware detection systems. As a widely used method in android malware detection, static detecting has been a hot topic in academia and industry. However, in order to improve the accuracy of detection, the existing static detecting methods sacrifice the excessively high analysis complexity and time cost. Moreover, the correlation between static features leads to redundancy of a large amount of data. Therefore, this paper proposes a static detecting method of Android malware based on sensitive pattern. It uses an improved FP-growth algorithm to mine frequent combinations of sensitive permissions and API calls in malicious apps and benign apps, which avoids the generation of redundant information. In addition, this paper adopts multi-layered gradient boosting decision trees algorithm to train the detection model. And a dual similarity combination method is proposed to measure the similarity between different sensitive patterns. The experimental results show that our proposed detection method has high accuracy and great generalization ability.

To better understand the formation of biogenic secondary organic aerosol (BSOA), aerosol samples with a 4 h time resolution were collected during summer and wintertime in the southeast of China, along with on-line measurements of trace gases, aerosol chemical compositions, and meteorological parameters. The samples were analyzed by gas chromatography-mass spectrometry for PM2.5-bound SOA tracers, including isoprene (SOAI), α/β-pinene (SOAM), β-caryophyllene (SOAC), and toluene (ASOA). The average concentrations of total SOA tracers in winter and summer were 38.8 and 111.9 ng m−3, respectively, with the predominance of SOAM (70.1 % and 45.8 %), followed by SOAI (14.0 % and 45.6 %), ASOA (11.0 % and 6.2 %) and SOAC (4.9 % and 2.3 %). Compare to those in winter, the majority of BSOA tracers in summer showed significant positive correlations with Ox (O3+NO2), HONO, ultraviolet (UV) and temperature (T), indicating the influence of photochemical oxidation under relatively clean conditions. However, in winter, BSOA tracers were significantly correlated with PM2.5, NO3-, SO42-, and NH3, attributed to the contributions of anthropogenic emissions. Major BSOA tracers in both seasons was linearly correlated with aerosol acidity (pH), liquid water content (LWC) and SO42-. The results indicated that acid-catalyzed reactive uptake onto sulfate aerosol particles enhanced the formation of BSOA. In summer, the clean air mass originated from the ocean, and chlorine depletion was observed. We also found that concentrations of the total SOA tracers was correlated with HCl and chlorine ions in PM2.5, reflecting the contribution of Cl-initiated VOC oxidations to the formation of SOA. In winter, the northeast dominant wind direction brought continental polluted air mass to the monitoring site, affecting the transformation of BSOA tracers. This implied that anthropogenic emissions, atmospheric oxidation capacity and halogen chemistry have significant effects on the formation of BSOA in the southeast coastal area.

Leukemogenesis is proposed to be a multistep process by which normal hematopoietic stem and progenitor cells are transformed into full-blown leukemic cells, the details of which are not fully understood. Here, we performed serial single-cell transcriptome analyses of preleukemic and leukemic cells (PLCs) and constructed the cellular and molecular transformation trajectory in a Myc-driven acute myeloid leukemia (AML) model in mice, which represented the transformation course in patients. We found that the Myc targets were gradually up-regulated along the trajectory. Among them were splicing factors, which showed stage-specific prognosis for AML patients. Furthermore, we dissected the detailed gene network of a tipping point for hematopoietic stem and progenitor cells (HSPCs) to generate initiating PLCs, which was characterized by dramatically increased splicing factors and unusual RNA velocity. In the late stage, PLCs acquired explosive heterogeneity through RNA alternative splicing. Among them, the Hsp90aa1hi subpopulation was conserved in both human and mouse AML and associated with poor prognosis. Exon 4 skipping of Tmem134 was identified in these cells. While the exon skipping product Tmem134β promoted the cell cycle, full-length Tmem134α delayed tumorigenesis. Our study emphasized the critical roles of RNA splicing in the full process of leukemogenesis.

Neuroinflammation is one of the most important pathological processes following brain ischemia. Pulsed electromagnetic fields (PEMFs) protect against brain ischemia, but their role in regulating neuroinflammation remains unclear. In the present study, we investigated the biological effects of PEMF exposure on brain ischemia-induced neuroinflammation through the astrocytic cholinergic anti-inflammatory pathway. PEMF exposure reduced the activation of astrocytes and neuroinflammation following brain ischemia by directly modulating astrocytic injury and inflammatory cytokine release. Inhibition of nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) by a specific antagonist reversed the regulatory effects of PEMF on astrocytes. Furthermore, negative regulation of signal transducer and activator of transcription 3 (STAT3) by α7nAChR was found to be an important downstream mechanism through which PEMF regulates astrocyte-related neuroinflammation. PEMF suppressed STAT3 phosphorylation and nuclear translocation by activating α7nAChR. These results demonstrate that PEMF exerts anti-inflammatory effects in the context of brain ischemia by modulating astrocytic α7nAChR/STAT3 signaling.

Excessive systemic inflammation plays a vital role in pathophysiology of preeclampsia (PE). The aim is to clarify the predictive value of the peripheral blood parameters including white blood cell (WBC), neutrophils, lymphocyte, monocyte, platelet count, mean platelet volume (MPV), plateletcrit, platelet distribution width (PDW), platelet-large cell ratio (PLCR), and the ratio value for PE.This retrospective study enrolled 170 PE patients, 123 healthy control pregnant women, and 122 non-pregnant women. When pregnant women were admitted to the hospital for delivery, peripheral complete blood cell count was detected by an automatic blood cell analyzer. Clinical signs and demographic characteristics were recorded. The receiver operating characteristic (ROC) curve was used to determine the cutoff value and analyze the predictive significances for PE. Furthermore, the risk factors of PE were tested by univariate and stratified analyses.This study showed that WBC, neutrophil count, neutrophil percentage, NLR, NMR, and PLR# were significantly increased in PE patients as compared with pregnant control patients (p0.001), whereas lymphocyte percentage, monocyte percentage, and PNR were decreased. In addition, there was no significant difference in the rest of the peripheral blood parameters between women with and without PE. The ROC curve result revealed that WBC and neutrophil count had a higher AUC value than the rest of peripheral blood variables. WBC and neutrophil count are positively correlated MAP. Moreover, the WBC and neutrophil count were indicated as independent risk factors for the development of PE.This study clarifies that peripheral blood parameters of WBC and neutrophil count have good applied value with high sensitivity and specificity in predicting the development of PE and are also independent risk factors for the development of PE.

Rapid, sensitive and specific detection of bacteria is of great importance. Herein, we developed a versatile biosensing platform for ultrasensitive detection of pathogenic bacteria, termed as SCENT-Cas (Silver nanoCluster Empowered Nucleic acids Test using CRISPR/Cas12a). Simply, the species-specific invA gene of Salmonella typhimurium (S. typhi) was isothermally amplified using LAMP, which subsequently triggered the trans-cleavage of CRISPR/Cas12a. The trans-cleavage degraded any single-stranded DNA (ssDNA) non-specifically. A DNA-templated AgNCs probe was then employed, in which green fluorescence emissive AgNCs effectively converted to red fluorescence emissive AgNCs when placed in close vicinity to a pre-designed converter ssDNA. As such, the trans-cleavage was utilized for shredding converter ssDNA, enabling the green-to-red fluorescent change to form a ratiometric biosensing platform. With this strategy, target nucleic acid was dexterously converted into ratiometric fluorescence that was recorded to detect as low as 1 CFU/mL S. typhi with a dynamic range from 1 to 10