[Retracted] MicroRNA­19b promotes the migration and invasion of ovarian cancer cells by inhibiting the PTEN/AKT signaling pathway.

[This retracts the article DOI: 10.3892/ol.2018.8695.].

RNA Control via Redox-Responsive Acylation.

Incorporating stimuli-responsive components into RNA constructs provides precise spatiotemporal control over RNA structures and functions. Despite considerable advancements, the utilization of redox-responsive stimuli for the activation of caged RNAs remains scarce. In this context, we present a novel strategy that leverages post-synthetic acylation coupled with redox-responsive chemistry to exert control over RNA. To achieve this, we design and synthesize a series of acylating reagents specifically tailored for introducing disulfide-containing acyl adducts into the 2'-OH groups of RNA ("cloaking"). Our data reveal that these acyl moieties can be readily appended, effectively blocking RNA catalytic activity and folding. We also demonstrate the traceless release and reactivation of caged RNAs ("uncloaking") through reducing stimuli. By employing this strategy, RNA exhibits rapid cellular uptake, effective distribution and activation in the cytosol without lysosomal entrapment. We anticipate that our methodology will be accessible to laboratories engaged in RNA biology and holds promise as a versatile platform for RNA-based applications.

SGLT2i improves kidney senescence by down-regulating the expression of LTBP2 in SAMP8 mice.

Senescent kidney can lead to the maladaptive repairment and predispose age-related kidney diseases. Here, we explore the renal anti-senescence effect of a known kind of drug, sodium-dependent glucose transporters 2 inhibitor (SGLT2i). After 4 months intragastrically administration with dapagliflozin on senescence-accelerated mouse prone 8 (SAMP8) strain mice, the physiologically effects (lowering urine protein, enhancing glomerular blood perfusion, inhibiting expression of senescence-related biomarkers) and structural changes (improving kidney atrophy, alleviating fibrosis, decreasing glomerular mesangial proliferation) indicate the potential value of delaying kidney senescence of SGLT2i. Senescent human proximal tubular epithelial (HK-2) cells induced by H2 O2 also exhibit lower senescent markers after dapagliflozin treatment. Further mechanism exploration suggests LTBP2 have the great possibility to be the target for SGLT2i to exert its renal anti-senescence role. Dapagliflozin down-regulate the LTBP2 expression in kidney tissues and HK-2 cells with senescent phenotypes. Immunofluorescence staining show SGLT2 and LTBP2 exist colocalization, and protein-docking analysis implies there is salt-bridge formation between them; these all indicate the possibility of weak-interaction between the two proteins. Apart from reducing LTBP2 expression in intracellular area induced by H2 O2 , dapagliflozin also decrease the concentration of LTBP2 in cell culture medium. Together, these results reveal dapagliflozin can delay natural kidney senescence in non-diabetes environment; the mechanism may be through regulating the role of LTBP2.

Fluorine-tailed glass fibers for adsorption of volatile perfluorinated compounds via F-F interaction.

Perfluorinated compounds (PFCs) and their short-chain derivatives are contaminants found globally. Adsorption research on volatile perfluorinated compounds (VPFCs), which are the main PFCs substances that undergo transfer and migration, is particularly important. In this study, new fluorine-containing tail materials (FCTMs) were prepared by combining fluorine-containing tail organic compounds with modified glass fibers. The adsorption effects of these FCTMs were generally stronger than that of pure activated glass fibers without fluorine- tailed, with an adsorption efficiency of up to 86% based on F-F interactions. The results showed that the FCTMs had improved desorption efficiency and reusability, and higher adsorption efficiency compared with that of polyurethane foam. FTGF was applied to the active sampler, and the indoor adsorption of perfluorovaleric acid was up to 2.45 ng/m3. The adsorption kinetics and isotherm simulation results showed that the adsorption process of typical perfluorinated compounds conformed to the second-order kinetics and Langmuir model. Furthermore, Nuclear Magnetic Resonance (NMR) results showed that the chemical shift in the fluorine spectrum was significantly changed by F-F interactions. This research provides basic theoretical data for the study of VPFCs, especially short-chain VPFCs, facilitating improved scientific support for the gas phase analysis of VPFCs in the environment.

The Comparation of Renal Anti-Senescence Effects and Blood Metabolites between Dapagliflozin and Metformin in Non-Diabetes Environment.

Delaying kidney senescence process will benefit renal physiologic conditions, and prompt the kidney recovering from different pathological states. The renal anti-senescence effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and metformin have been proven in diabetic settings, but the roles of each one and combination of two drugs in natural kidney aging process remain undefined and deserve further research. Senescence-accelerated mouse prone 8 (SAMP8) were orally administered dapagliflozin, metformin, and a combination of them for 16 weeks. Dapagliflozin exhibits better effects than metformin in lowering senescence related markers, and the combination therapy shows the best results. In vitro experiments demonstrate the same results that the combination of dapagliflozin and metformin can exert a better anti-senescence effect. Blood metabolites detection in vivo shows dapagliflozin mainly leads to the change of blood metabolites enriched in choline metabolism, and metformin tends to induce change of blood metabolites enriched in purine metabolism. In conclusion, the results suggest dapagliflozin may have a better renal anti-senescence effect than metformin in non-diabetes environment, and the combination of the two drugs can strengthen the effect. The two drugs can lead to different blood metabolites alteration, which may lead to different systemic effects.

Synergetic Monitoring of both Physiological Pressure and Epidermal Biopotential Based on a Simplified on-Skin-Printed Sensor Modality.

Flexible electronic sensors show great potential for health monitoring but are usually limited to single sensing functionality. To enrich their functions, complicated device configurations, sophisticated material systems, and preparation processes are typically involved, obstructing their large-scale deployment and widespread application. Herein, to achieve a good balance between simplicity and multifunctionality, a new paradigm of sensor modality for both mechanical sensing and bioelectrical sensing is presented based on a single material system and a simple solution processing approach. The whole multifunctional sensors are constructed with a pair of highly conductive ultrathin electrodes (WPU/MXene-1) and an elastic micro-structured mechanical sensing layer (WPU/MXene-2), with the human skin serving as the substrate for the whole sensors. The resultant sensors show high pressure sensitivity and low skin-electrode interfacial impedance, enabling to synergetically monitor both physiological pressure (e.g., arterial pulse signals) and epidermal bioelectrical signals (including electrocardiograph and electromyography). The universality and extensibility of this methodology to construct multifunctional sensors with different material systems are also verified. This simplified sensor modality with enhanced multifunctionality provides a novel design concept to construct future smart wearables for health monitoring and medical diagnosis.

An Android Malware Detection Approach to Enhance Node Feature Differences in a Function Call Graph Based on GCNs.

The smartphone has become an indispensable tool in our daily lives, and the Android operating system is widely installed on our smartphones. This makes Android smartphones a prime target for malware. In order to address threats posed by malware, many researchers have proposed different malware detection approaches, including using a function call graph (FCG). Although an FCG can capture the complete call-callee semantic relationship of a function, it will be represented as a huge graph structure. The presence of many nonsensical nodes affects the detection efficiency. At the same time, the characteristics of the graph neural networks (GNNs) make the important node features in the FCG tend toward similar nonsensical node features during the propagation process. In our work, we propose an Android malware detection approach to enhance node feature differences in an FCG. Firstly, we propose an API-based node feature by which we can visually analyze the behavioral properties of different functions in the app and determine whether their behavior is benign or malicious. Then, we extract the FCG and the features of each function from the decompiled APK file. Next, we calculate the API coefficient inspired by the idea of the TF-IDF algorithm and extract the sensitive function called subgraph (S-FCSG) based on API coefficient ranking. Finally, before feeding the S-FCSG and node features into the GCN model, we add the self-loop for each node of the S-FCSG. A 1-D convolutional neural network and fully connected layers are used for further feature extraction and classification, respectively. The experimental result shows that our approach enhances the node feature differences in an FCG, and the detection accuracy is greater than that of models using other features, suggesting that malware detection based on a graph structure and GNNs has a lot of space for future study.

Bioinspired Tactile Sensation Based on Synergistic Microcrack-Bristle Structure Design toward High Mechanical Sensitivity and Direction-Resolving Capability.

Natural tactile sensation is complex, which involves not only contact force intensity detection but also the perception of the force direction, the surface texture, and other mechanical parameters. Nevertheless, the vast majority of the developed tactile sensors can only detect the normal force, but usually cannot resolve shear force or even distinguish the directions of the force. Here, we present a new paradigm of bioinspired tactile sensors for resolving both the intensity and the directions of mechanical stimulations via synergistic microcrack-bristle structure design and cross-shaped configuration engineering. The microcrack sensing structure gives high mechanical sensitivity to the tactile sensors, and the synergistic bristle structure further amplifies the sensitivity of the sensors. The cross-shaped configuration engineering of the synergistic microcrack-bristle structure further endows the tactile sensors with good capability to detect and distinguish the directions of the applied mechanical forces. The as-fabricated tactile sensors exhibit a high sensitivity (25.76 N-1), low detection limit (5.4 mN), desirable stability (over 2,500 cycles), and good capability to resolve both mechanical intensity and directional features. As promising application scenarios, surface texture recognition and biomimetic path explorations are successfully demonstrated with these tactile sensors. This newly proposed tactile sensation strategy and technology have great potential applications in ingenious tactile sensation and construction of various robotic and bionic prostheses with high operational dexterity.

TSFN: A Novel Malicious Traffic Classification Method Using BERT and LSTM.

Traffic classification is the first step in network anomaly detection and is essential to network security. However, existing malicious traffic classification methods have several limitations; for example, statistical-based methods are vulnerable to hand-designed features, and deep learning-based methods are vulnerable to the balance and adequacy of data sets. In addition, the existing BERT-based malicious traffic classification methods only focus on the global features of traffic and ignore the time-series features of traffic. To address these problems, we propose a BERT-based Time-Series Feature Network (TSFN) model in this paper. The first is a Packet encoder module built by the BERT model, which completes the capture of global features of the traffic using the attention mechanism. The second is a temporal feature extraction module built by the LSTM model, which captures the time-series features of the traffic. Then, the global and time-series features of the malicious traffic are incorporated together as the final feature representation, which can better represent the malicious traffic. The experimental results show that the proposed approach can effectively improve the accuracy of malicious traffic classification on the publicly available USTC-TFC dataset, reaching an F1 value of 99.50%. This shows that the time-series features in malicious traffic can help improve the accuracy of malicious traffic classification.

Recent Progress in Modifications, Properties, and Practical Applications of Glass Fiber.

As a new member of the silica-derivative family, modified glass fiber (MGF) has attracted extensive attention because of its excellent properties and potential applications. Surface modification of glass fiber (GF) greatly changes its performance, resulting in a series of changes to its surface structure, wettability, electrical properties, mechanical properties, and stability. This article summarizes the latest research progress in MGF, including the different modification methods, the various properties, and their advanced applications in different fields. Finally, the challenges and possible solutions were provided for future investigations of MGF.

Transcriptomic and metabolomic insights into the defense response to HFRs in Arabidopsis.

Tetrabromobisphenol A (TBBPA), Tetrachlorobisphenol A (TCBPA), Tetrabromobisphenol S (TBBPS) and their derivatives as the most widely used halogenated flame retardants (HFR), had been employed in the manufacturing industry to raise fire safety. HFRs have been shown to be developmentally toxic to animals and also affect plant growth. However, little was known about the molecular mechanism responded by when plants were treated with these compounds. In this study, when Arabidopsis was exposed to four HFRs (TBBPA, TCBPA, TBBPS-MDHP, TBBPS), the stress of these compounds had different inhibitory effects on seed germination and plant growth. Transcriptome and metabolome analysis showed that all four HFRs could influence the expression of transmembrane transporters to affect ion transport, Phenylpropanoid biosynthesis, Plant-pathogen interaction, MAPK signalling pathway and other pathways. In addition, the effects of different kinds of HFR on plants also have variant characteristics. It is very fascinating that Arabidopsis shows the response of biotic stress after exposure to these kinds of compounds, including the immune mechanism. Overall, the findings of the mechanism recovered by methods of transcriptome and metabolome analysis supplied a vital insight into the molecular perspective for Arabidopsis response to HFRs stress.

Core-binding factor fusion downregulation of ADAR2 RNA editing contributes to AML leukemogenesis.

Adenosine-to-inosine RNA editing, which is catalyzed by adenosine deaminases acting on RNA (ADAR) family of enzymes, ADAR1 and ADAR2, has been shown to contribute to multiple cancers. However, other than the chronic myeloid leukemia blast crisis, relatively little is known about its role in other types of hematological malignancies. Here, we found that ADAR2, but not ADAR1 and ADAR3, was specifically downregulated in the core-binding factor (CBF) acute myeloid leukemia (AML) with t(8;21) or inv(16) translocations. In t(8;21) AML, RUNX1-driven transcription of ADAR2 was repressed by the RUNX1-ETO additional exon 9a fusion protein in a dominant-negative manner. Further functional studies confirmed that ADAR2 could suppress leukemogenesis specifically in t(8;21) and inv16 AML cells dependent on its RNA editing capability. Expression of 2 exemplary ADAR2-regulated RNA editing targets coatomer subunit α and component of oligomeric Golgi complex 3 inhibits the clonogenic growth of human t(8;21) AML cells. Our findings support a hitherto, unappreciated mechanism leading to ADAR2 dysregulation in CBF AML and highlight the functional relevance of loss of ADAR2-mediated RNA editing to CBF AML.

SIRT3 inhibition suppresses hypoxia-inducible factor 1α signaling and alleviates hypoxia-induced apoptosis of type B spermatogonia GC-2 cells.

Hypoxia has been reported to be an important factor leading to male infertility, and it has been reported that hypoxia can induce the apoptosis of mouse spermatogenic cells. Sirtuin 3 (SIRT3) has been reported to promote the degradation of hypoxia-inducible factor 1α (HIF-1α), and thus, we hypothesized that SIRT3 may influence hypoxia-induced apoptosis of spermatogonia. In this study, we overexpressed or inhibited SIRT3 in mouse type B spermatogonia GC-2 cells and then subjected the cells to hypoxia or normoxia, before examining hypoxia-responsive gene expression and cell viability. We report that SIRT3 stabilizes hypoxia-inducible factor 1α (HIF-1α) and activates its downstream target gene expression in GC-2 cells. We also show that the SIRT3 inhibitor 3-TYP suppresses HIF-1α target gene expression and alleviates hypoxia-induced apoptosis of GC-2 cells. Our study reveals the critical role and underlying mechanisms of SIRT3 in hypoxia-induced apoptosis of mouse type B spermatogonia GC-2 cells.

Adherence to High Dietary Diversity and Incident Cognitive Impairment for the Oldest-Old: A Community-Based, Nationwide Cohort Study.

BACKGROUND AND AIMS: Dietary diversity change is associated with cognitive function, however, whether the effect still exists among the oldest-old (80+) is unclear. Our aim was to examine the effect of dietary diversity changes on cognitive impairment for the oldest-old in a large prospective cohort. METHODS: Within the Chinese Longitudinal Healthy Longevity Study, 6237 adults older than 80 years were included. The dietary diversity score (DDS) was assessed by a simplified food frequency questionnaire (FFQ). Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score lower than 18 points. Cognitive decline was defined as a reduction of total MMSE score ≥3 points, and cognitive decline of different subdomains was defined as a reduction of ≥15% in the corresponding cognitive domain. The multivariate-adjusted Cox proportional hazard model evaluated the effects of DDS change on cognitive decline. The linear mixed-effect model was used to test subsequent changes in MMSE over the years. RESULTS: During 32,813 person-years of follow-up, 1829 participants developed cognitive impairment. Relative to the high-high DDS change pattern, participants in the low-low and high-low patterns were associated with an increased risk of cognitive impairment with a hazard ratio (95% confidential interval, CI) of 1.43 (1.25, 1.63) and 1.44 (1.24, 1.67), and a faster decline in the MMSE score over the follow-up year. Participants with the low-high pattern had a similar incidence of cognitive impairment with HRs (95% CI) of 1.03 (0.88, 1.20). Compared with the stable DDS status group (-1-1), the risk of cognitive impairment was higher for those with large declines in DDS (≤-5) and the HR was 1.70 (95% CI: 1.44, 2.01). CONCLUSIONS: Even for people older than 80, dietary diversity change is a simple method to identify those who had a high risk of cognitive decline. Keeping high dietary diversity is beneficial for cognitive function and its subdomain even in the final phase of life, especially for females and the illiterate oldest-old.

The optimal exercise modality and intensity for hemodialysis patients incorporating Bayesian network meta-analysis and systematic review.

Background: Physical inactivity is highly prevalent in patients with hemodialysis, and a large body of evidence reported the positive effect of different exercise modalities on their health outcomes. However, the effective dosage of exercise for hemodialysis patients still requires verification. Objective: We aimed to determine the most effective exercise intensity and modality for improvements in physical function, blood pressure control, dialysis adequacy, and health-related quality of life for hemodialysis patients. Design: Systematic review with network meta-analysis of randomized trials. Data sources: Five electronic databases (PubMed, EMBASE, Web of Science, Cochrane CENTRAL, and Scopus) were searched for randomized controlled trials. Data extraction and quality appraisal were conducted by two authors independently. Data were analyzed by the R (version.3.6.2) and the Stata (version.15.0). Result: We included 1893 patients involving four exercise modalities and six exercise intensities. Combined training (aerobic exercise plus resistance exercise) has been the top-ranking exercise modality for improving the 6-min walk test (6MWT) (surface under the cumulative ranking curve analysis (SUCRA) score, 90.63), systolic blood pressure control (SUCRA score, 77.35), and diastolic pressure control (SUCRA score, 90.56). Moreover, the top-ranking exercise intensity was moderate-vigorous for 6MWT (SUCRA score, 82.36), systolic blood pressure (SUCRA score, 77.43), and diastolic blood pressure (SUCRA score, 83.75). Regarding dialysis adequacy and health-related quality of life, we found no exercise modality or intensity superior to the placebo. Conclusion: This network meta-analysis indicated that combined training and moderate-vigorous intensity might be the most effective interventions to improve 6MWT and blood pressure control. This finding helps further guide clinical exercise prescriptions for hemodialysis patients. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021268535].

[Effect of Xingnao Kaiqiao acupuncture on safety of rt-PA intravenous thrombolysis in patients with cerebral infarction: a randomized controlled trial].

OBJECTIVE: To assess the effect of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on the efficacy and safety of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with cerebral infarction. METHODS: A total number of 142 patients of cerebral infarction undergoing rt-PA intravenous thrombolysis were randomized into an acupuncture-medication group (71 cases) and a western medication group (71 cases, 1 case dropped off). In the western medication group, rt-PA intravenous thrombolysis was given. In the acupuncture-medication group, besides the intervention as the control group, Xingnao Kaiqiao acupuncture was provided at Shuigou (GV 26), Neiguan (PC 6), Sanyinjiao (SP 6), Jiquan (HT 1), etc. once daily. One treatment session contained 6 treatments and 1 session was required. Before and after treatment, the score of the National Institute of Health stroke scale (NIHSS), the levels of the relevant indexes of symptomatic intracerebral hemorrhage (sICH) (platelet [PLT], D-dimer and fibrinogen), the incidences of sICH and adverse effect were compared between groups. The efficacy was assessed in two groups. RESULTS: After treatment, NIHSS scores and the levels of D-dimer were reduced compared with those before treatment in both groups (P<0.05), and those in the acupuncture-medication group were lower than the western medication group (P<0.05). The level of fibrinogen in the acupuncture-medication group was increased in comparison with that before treatment (P<0.05), and also higher than the western medication group (P<0.05). The incidence of sICH was 0% (0/71) in the acupuncture-medication group, lower than 8.6% (6/70) in the western medication group (P<0.05). The effective rate was 97.2% (69/71) in the acupuncture-medication group, higher than 87.1% (61/70) in the western medication group (P<0.05). The incidence of adverse effect was 2.8% (2/71) in the acupuncture-medication group, lower than 12.9% (9/70) in the western medication group (P<0.05). CONCLUSION: Xingnao Kaiqiao acupuncture may improve the efficacy of rt-PA intravenous thrombolysis in the patients with cerebral infraction and decrease the incidences of sICH and adverse effect. The mechanism may be related to the regulation of fibrinogen and D-dimer levels.

Slowed down nitrogen mineralization under bacterial community-driven conditions by adding inhibitors during rice straw composting.

The aim of this paper was to confirm the role of inhibitors addition, namely adenosine triphosphate (ATP) and malonic acid (MA), on nitrogen availability during rice straw (RS) composting. The results showed that inhibitors addition slowed down the mineralization of ammonium nitrogen and nitrate nitrogen compared to CK. Meanwhile, amino sugar nitrogen and hydrolysable unknown nitrogen contents in ATP and MA treatments were higher, indicating that their addition improved the retention of organic nitrogen components. Furthermore, inhibitors additions attenuated the responsive relationship between bacterial communities and nitrogen components. The main reason was that the addition changed the bacterial community structure of RS compost. The final structural equation verified that inhibitors addition enhanced conversion between nitrogen components, that was, to complex nitrogen components to improve the quality of compost, and the remodeling of bacterial community played an important role. Therefore, adding inhibitors had a driving effect on promoting nitrogen sequestration.

Multilayered control of splicing regulatory networks by DAP3 leads to widespread alternative splicing changes in cancer.

The dynamic regulation of alternative splicing requires coordinated participation of multiple RNA binding proteins (RBPs). Aberrant splicing caused by dysregulation of splicing regulatory RBPs is implicated in numerous cancers. Here, we reveal a frequently overexpressed cancer-associated protein, DAP3, as a splicing regulatory RBP in cancer. Mechanistically, DAP3 coordinates splicing regulatory networks, not only via mediating the formation of ribonucleoprotein complexes to induce substrate-specific splicing changes, but also via modulating splicing of numerous splicing factors to cause indirect effect on splicing. A pan-cancer analysis of alternative splicing across 33 TCGA cancer types identified DAP3-modulated mis-splicing events in multiple cancers, and some of which predict poor prognosis. Functional investigation of non-productive splicing of WSB1 provides evidence for establishing a causal relationship between DAP3-modulated mis-splicing and tumorigenesis. Together, our work provides critical mechanistic insights into the splicing regulatory roles of DAP3 in cancer development.

ADARs act as potent regulators of circular transcriptome in cancer.

Circular RNAs (circRNAs) are produced by head-to-tail back-splicing which is mainly facilitated by base-pairing of reverse complementary matches (RCMs) in circRNA flanking introns. Adenosine deaminases acting on RNA (ADARs) are known to bind double-stranded RNAs for adenosine to inosine (A-to-I) RNA editing. Here we characterize ADARs as potent regulators of circular transcriptome by identifying over a thousand of circRNAs regulated by ADARs in a bidirectional manner through and beyond their editing function. We find that editing can stabilize or destabilize secondary structures formed between RCMs via correcting A:C mismatches to I(G)-C pairs or creating I(G).U wobble pairs, respectively. We provide experimental evidence that editing also favors the binding of RNA-binding proteins such as PTBP1 to regulate back-splicing. These ADARs-regulated circRNAs which are ubiquitously expressed in multiple types of cancers, demonstrate high functional relevance to cancer. Our findings support a hitherto unappreciated bidirectional regulation of circular transcriptome by ADARs and highlight the complexity of cross-talk in RNA processing and its contributions to tumorigenesis.

Platelet-biomimetic nanoparticles for in vivo targeted photodynamic therapy of breast cancer.

Nanocarrier-based photodynamic therapy (PDT) has emerged as a promising treatment in cancer therapy. However, the PDT therapeutic efficacy is limited by the lack of specificity, limited intracellular cytotoxic reactive oxygen species (ROS) generation, and the immunosuppressive tumor microenvironment. Herein, a platelet membrane (Pm) decorated and chlorin e6 loaded liposome (Pm/Lps/Ce6) is developed to improve specific tumor-targeting capability and antitumor responses. Pm/Lps/Ce6 could efficiently improve the cellular internalization of Ce6. Under 660-nm laser irradiation, enough ROS was produced to suppress the growth of tumor cells in vitro. In vivo, the Pm decoration increased cellular uptake of the Ce6 loaded liposome in cancer cells by the tumor-targeting and immune escape capacity and produced a satisfactory inhibitory effect on breast cancer. Our study provides a biomimetic strategy via the biological properties of Pm to improve the antitumor performance of photodynamic therapy for treating breast cancer.