Optimal time point for neutrophil-to-lymphocyte ratio to predict stroke-associated pneumonia.

PURPOSE: This study aimed at the population receiving thrombolytic therapy and to explore the optimal time point for neutrophil-to-lymphocyte ratio (NLR) in predicting stroke-associated pneumonia (SAP). METHODS: We assessed patients undergoing intravenous thrombolysis (IVT) for acute ischemic stroke. Blood parameters were sampled before thrombolysis (within 30 min after admission) and within 24-36 h after thrombolysis, respectively. The primary outcome measure was the occurrence of SAP. Multivariate logistic regression analysis was performed to analyze the association between admission blood parameters and the event of SAP. We also used receiver operating characteristic (ROC) curve analysis to assess the discriminative ability of blood parameters measured at different times in predicting SAP. RESULTS: Among the 388 patients, SAP occurred in 60 (15%) patients. Multivariate logistic regression analysis showed that NLR was significantly associated with SAP (NLR before IVT: aOR = 1.288; 95%CI = 1.123-1.476; p < 0.001; NLR after IVT: (aOR = 1.127, 95%CI = 1.017-1.249; p = 0.023). The ROC curve showed that the predictive ability of NLR after IVT was better than NLR before IVT, not only in predicting the occurrence of SAP but also in predicting short-term and long-term functional outcomes, hemorrhagic transformation, and 1-year mortality. CONCLUSION: Increased NLR measured within 24-36 h after IVT has a significant predictive effect on the occurrence of SAP and can be used to predict short-term and long-term poor functional outcomes, hemorrhagic transformation, and 1-year mortality.

A Secured Proxy-Based Data Sharing Module in IoT Environments Using Blockchain.

Access and utilization of data are central to the cloud computing paradigm. With the advent of the Internet of Things (IoT), the tendency of data sharing on the cloud has seen enormous growth. With data sharing comes numerous security and privacy issues. In the process of ensuring data confidentiality and fine-grained access control to data in the cloud, several studies have proposed Attribute-Based Encryption (ABE) schemes, with Key Policy-ABE (KP-ABE) being the prominent one. Recent works have however suggested that the confidentiality of data is violated through collusion attacks between a revoked user and the cloud server. We present a secured and efficient Proxy Re-Encryption (PRE) scheme that incorporates an Inner-Product Encryption (IPE) scheme in which decryption of data is possible if the inner product of the private key, associated with a set of attributes specified by the data owner, and the associated ciphertext is equal to zero 0 . We utilize a blockchain network whose processing node acts as the proxy server and performs re-encryption on the data. In ensuring data confidentiality and preventing collusion attacks, the data are divided into two, with one part stored on the blockchain network and the other part stored on the cloud. Our approach also achieves fine-grained access control.

Molecular cloning and functional analysis of tumor necrosis factor receptor-associated factor 6 (TRAF6) in thick shell mussel, Mytilus coruscus.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is one of the key adapter molecules in Toll-like receptor signal transduction that triggers downstream cascades involved in innate immunity. Despite of the well study in vertebrates, there is few data ascribe to this TRAF member in invertebrates, especially in bivalves. In the present study, a novel TRAF6 homologue termed McTRAF6 was firstly characterized in Mytilus coruscus. Like its counterparts in mammals, McTRAF6 shared the domain topology containing one RING domain, two zinc finger domains, one coiled-coil region and a MATH domain. McTRAF6 transcripts predominantly expressed in gills, digestive glands and hemocytes in M. coruscus, and were significantly up-regulated in hemocytes after challenge with lipopolysaccharide (LPS) and polyinosine-polycytidylic acid (poly I:C). Further, the subcellular localization in cytoplasm and the activation of Nk-κB or ISRE luciferase reporter by overexpressed McTRAF6 were identified in HEK293T cells. These results collectively indicate that McTRAF6 is a member of TRAF6 subfamily and plays a potential role in immune defense system against pathogenic agents invasions in thick shell mussel. To our knowledge, this is the first report on component of TLR signaling pathway in thick shell mussel, providing further evidence for the existence of TLR pathway in M. coruscus and contribute to clarify the innate immune system of thick shell mussel.

Identification and functional characterization of three myeloid differentiation factor 88 (MyD88) isoforms from thick shell mussel Mytilus coruscus.

Myeloid differentiation factor 88 (MyD88) is a pivotal adapter protein that involved in interleukin-1 receptor/toll-like receptor (IL-1R/TLR) signal transduction, which could spur downstream cascades and eventually drawn into innate immune response. MyD88 has been extensively studied in vertebrates, however, the information ascribe to MyD88 in invertebrates is still very scarce especially its function annotation remains extremely obscure. At here, three novel MyD88 isoforms termed McMyD88a, McMyD88b and McMyD88c were firstly cloned from thick shell mussel Mytilus coruscus. McMyD88a, McMyD88b and McMyD88c shared domain topology containing the Death domain (DD) and TIR domain (TIR) with its counterparts in mammals. All three McMyD88s were ubiquitously expressed in examined tissues in thick shell mussel, with the higher expression levels in immune-related tissues such as haemocytes, gills and digestive glands. Upon Vibrio alginolyticus, polyinosine-polycytidylic acid (poly I:C) and lipopolysaccharide (LPS) challenge, McMyD88a, McMyD88b and McMyD88c transcripts were significantly induced in haemocytes despite of differential expression levels and responsive time points. Overexpression of McMyD88a, McMyD88b and McMyD88c showed a dose-dependent induction to NF-κB or ISRE in mammalian cell lines. Taken together, these results suggested that McMyD88a, McMyD88b and McMyD88c are members of MyD88 family and play potential roles in innate immune response to pathogenic invasions in thick shell mussel. Moreover, these results suggested indirectly the existence of a MyD88-dependent signaling pathway in thick shell mussel, and provide insight into the immunoregulatory effect in molluscs.

Effects of low concentrations copper on antioxidant responses, DNA damage and genotoxicity in thick shell mussel Mytilus coruscus.

For the aim to study potential detrimental effects induced by Cu exposure at low, environmentally relevant concentrations, the in vivo activities at different levels of biological organisations of thick shell mussel Mytilus coruscus exposed to two levels of copper were assessed. Cu-induced stresses were evaluated through antioxidant responses, DNA damage and genotoxicity. The results revealed significant higher SOD and CAT activities, and MDA concentration in haemocytes of M. coruscus with Cu exposure at 8 µg/L, while only significant accumulation in CAT activity with Cu exposure at 2 µg/L and no significant changes with SOD activity and MDA concentration at this level of Cu exposure. Copper exposure induced DNA damage as induction of OTM value in a time- and concentration-dependent manner. In addition, copper exposure could significantly induced the expressions of MT-10, Hsp70, Hsp90 and C3. The present results deepen the mussels as a suitable model marine invertebrate species to study potential detrimental effects induced by possible toxicants, in combinations at different levels of biological organisations.

Effects of dietary toxic cyanobacteria and ammonia exposure on immune function of blunt snout bream (Megalabrama amblycephala).

Cyanobacterial blooms caused by water eutrophication have become a worldwide problem. During the degradation of toxic cyanobacterial blooms, elevated ammonia and microcystins concentrations co-occur and exert toxicity on fish. Up to now, the combined effect of microcystins and ammonia on fish immunotoxicity has not been reported. The present study investigated immune responses of blunt snout bream (Megalabrama amblycephala) to dietary toxic cyanobacteria and ammonia exposure. Megalobrama amblycephala were exposed to solutions with different concentrations of NH3-N (0, 0.06, 0.12 mg/L) and fed with diets containing 15% and 30% of toxic cyanobacteria lyophilized powder for 30 d. The microcystins concentration in different organs of Megalobrama amblycephala was in the following sequence: head kidney > liver > intestine > gonad > spleen > gill > trunk kidney > brain > muscle > heart. In both head kidney and spleen, the MC-LR and MC-RR concentration increased significantly with increasing NH3-N concentration. It indicates that NH3-N maybe promote the accumulation of microcystins in immune organs of Megalobrama amblycephala. Meanwhile, broadened peripheral interspace of lymphocytes, nucleus shrivel and edematous mitochondria were observed in head kidney lymphocyte of toxic treatment fish. Moreover, there were significant interactions between dietary toxic cyanobacteria and ammonia exposure on head kidney macrophage phagocytosis activity, respiratory burst activities, total number of white blood cells and the transcriptional levels of sIgM, mIgD and sIgZ genes. Our data clearly demonstrated that dietary toxic cyanobacteria combined with ammonia exposure showed a synergistic effect on Megalobrama amblycephala immunotoxicity.

Determination of Risk Factors and Establishment of a Prediction Model for Immediate Technical Failure during Endovascular Treatment of Femoropopliteal Occlusive Disease.

BACKGROUND: For long femoropopliteal occlusive lesions, the immediate technical failure (ITF) of endovascular treatment (EVT) is relatively high. Therefore, this study aims to reveal risk factors and establish a prediction model of ITF of EVT in femoropopliteal occlusive disease (FPOD) patients based on preoperative clinical date that may be helpful to the clinical procedures. METHODS: A retrospective analysis of 1,563 FPOD patients who underwent above-the-knee EVT was undertaken. Univariate analysis with chi-squared test was used to screen risk factors from preoperative clinical data. Multivariable analysis with logistic regression was used to generate a model for predicting the ITF rate of EVT, which was evaluated through the receiver operating characteristic curve and another independent cohort of 242 FPOD patients. RESULTS: Risk factors for ITF during EVT in FPOD included age (>80 years, X1), the absence of diabetes mellitus (X2), low-density lipoprotein (>160 mg/dL, X3), lesion calcification (X4), lesion length (>20 cm, X5), ostial occlusion of superficial femoral artery (SFA) (X6), and SFA lesion involving the popliteal artery (X7). A logistic regression model was established based on the equation: -6.504 + 1.236X1 + 0.945X2 + 1.406X3 + 1.136X4 + 1.059X5 + 2.307X6 + 2.194X7. Scores were given to risk factors as follows: X1 (yes = 12, no = 0), X2 (yes = 9, no = 0), X3 (yes = 14, no = 0), X4 (yes = 11, no = 0), X5 (yes = 11, no = 0), X6 (yes = 23, no = 0), and X7 (yes = 22, no = 0). We determined that the optimal comprehensive score for predicting EVT failure was 39, with a sensitivity of 0.847 and a specificity of 0.8. Among these 242 peripheral arterial disease patients, 12 of 14 patients who had failed EVT had a comprehensive score of >39. CONCLUSIONS: We identified a number of risk factors of ITF during the above-the-knee EVT and established a prediction model that may be used for guidance in clinical practice.

Multi-piecewise quadratic nonlinearity memristor and its 2N-scroll and 2N + 1-scroll chaotic attractors system.

In this paper, two kinds of novel ideal active flux-controlled smooth multi-piecewise quadratic nonlinearity memristors with multi-piecewise continuous memductance function are presented. The pinched hysteresis loop characteristics of the two memristor models are verified by building a memristor emulator circuit. Using the two memristor models establish a new memristive multi-scroll Chua's circuit, which can generate 2N-scroll and 2N+1-scroll chaotic attractors without any other ordinary nonlinear function. Furthermore, coexisting multi-scroll chaotic attractors are found in the proposed memristive multi-scroll Chua's circuit. Phase portraits, Lyapunov exponents, bifurcation diagrams, and equilibrium point analysis have been used to research the basic dynamics of the memristive multi-scroll Chua's circuit. The consistency of circuit implementation and numerical simulation verifies the effectiveness of the system design.

Effects of toxic cyanobacteria and ammonia on flesh quality of blunt snout bream (Megalobrama amblycephala).

BACKGROUND: Toxic cyanobacterial blooms result in the production of an organic biomass containing cyanotoxins (e.g. microcystins) and an elevated ammonia concentration in the water environment. The ingestion of toxic cyanobacteria and exposure to ammonia are grave hazards for fish. The present study assessed the effects of dietary toxic cyanobacteria and ammonia exposure on the flesh quality of blunt snout bream (Megalobrama amblycephala). RESULTS: Dietary toxic cyanobacteria and ammonia exposure had no impact on fish growth performance, fillet proximate composition and drip loss, whereas it significantly decreased fillet total amino acids, total essential amino acids, hardness and gumminess, and increased fillet ultimate pH as well as malondialdehyde content. However, there was no significant interaction between dietary toxic cyanobacteria and ammonia exposure on these parameters. Additionally, dietary toxic cyanobacteria significantly increased fillet initial pH, thaw loss and protein carbonyl content, whereas ammonia exposure did not. CONCLUSION: The results of the present study indicate that dietary toxic cyanobacteria and ammonia exposure reduced the quality of blunt snout bream fillet. © 2016 Society of Chemical Industry.

The effect of Aeromonas hydrophila infection on the non-specific immunity of blunt snout bream (Megalobrama amblycephala).

Aeromonas hydrophila is the main reason of epidemic septicaemia for freshwater fish. In the present study, the effect of Aeromonas hydrophila infection on the non-specific immunity of blunt snout bream (Megalobrama amblycephala) was studied. After Aeromonas hydrophila challenge, lysozyme activity was significantly increased at 4 h, 1 d, 3 d, 5 d, 14 d and 21 d. An increased level of lysozyme activity indicated a natural protective mechanism in fish. The significant increases of superoxide dismutase activity and catalase activity in treatment group were detected at 4 h, 1 d, 3 d, 5 d, 14 d and 21 d after Aeromonas hydrophila challenge. Increase in the superoxide anion and H2O2 is considered to be beneficial for self-protection from disease. Acid phosphatase activity increased significantly at 1 d, 3 d and 5 d after Aeromonas hydrophila challenge. Alkaline phosphatase activity in treatment group showed significant increase at 4 h, 1 d, 3 d, 5 d, 14 d and 21 d compared to control group. Increased phosphatase activity indicates higher breakdown of the energy reserve, which is utilized for the growth and survival of fish. These results revealed that the non-specific immunity of fish played an important role in self-protection after pathogens infection.

sIgZ exhibited maternal transmission in embryonic development and played a prominent role in mucosal immune response of Megalabrama amblycephala.

IgZ is considered to be the last immunoglobulin discovered in vertebrate species. In this study, the structure of secreted form of blunt snout bream (Megalabrama amblycephala) IgZ (sIgZ) heavy chain gene is VH-Cζ1-Cζ2-Cζ3-Cζ4, in which Cζ4 provides the specificity to the IgZ isotype. The deduced amino acid sequence of sIgZ shows highest similarity with that of Ctenopharyngodon idella (79%). The ontogeny of sIgZ gene expression showed a V-shape change pattern: decreased initially from unfertilized egg stage to 16-cell embryos and increased significantly from blastula stage, which exhibited maternal transmission effects. Compared with the juvenile fish, sIgZ mRNA level was higher in head kidney, spleen, trunk kidney, liver, intestine and gill of adult fish. In both juvenile and adult fish, sIgZ mRNA was detected in intestine and gill. Aeromonas hydrophila challenge experiment showed that sIgZ transcription significantly increased in skin, gill and intestine, indicating a prominent mucosal immune response. The results of Western blot also verified the protein alterations of sIgZ in mucosal organs in M. amblycephal. Our studies indicate a prominent role of IgZ in mucosa-associated lymphoid tissue immunity and further support the specialized role of IgZ in teleost mucosal immune responses.

Spatio-temporal expression of blunt snout bream (Megalobrama amblycephala) mIgD and its immune response to Aeromonas hydrophila.

The function of IgD in fish and mammals has not been fully understood since its discovery. In this study, we have isolated and characterized the cDNA that encodes membrane-bound form of the immunoglobulin D heavy chain gene (mIgD) of blunt snout bream (Megalobrama amblycephala) using RT-PCR and rapid amplification of cDNA ends (RACE). The full-length cDNA of mIgD consisted of 3313 bp, encoding a putative protein of 943 amino acids. The structure of blunt snout bream mIgD is VDJ-µ1-δ1-δ2-δ3-δ4-δ5-δ6-δ7-TM. Multiple alignment and phylogenetic analyses indicated that blunt snout bream mIgD clusters with the homologues of cyprinid fish and that its highest identity is with that of C. idella (82%). The mIgD expression in early different developmental stages showed that the level of mIgD mRNA decreased dramatically from the unfertilized egg stage to the 32-cell stage, suggesting that mIgD mRNA was maternally transferred. As cell differentiation initially took place in the blastula stage, the mIgD expression increased significantly from the blastula stage to prelarva, which might be attributed to embryonic stem cell differentiation processes. Compared with juvenile fish, the expression and tissue distribution patterns of mIgD in adult individuals exhibited considerable variation. After the injection of Aeromonas hydrophila, mIgD expression was up-regulated in various tissues, reaching the peak expression at 5 d, 14 d or 21 d (depending on the tissue type). The present study provides a theoretical basis for further research of the teleost immune system.

Molecular cloning and expression analysis of immunoglobulin M heavy chain gene of blunt snout bream (Megalobrama amblycephala).

Immunoglobulins (Igs), which bind antigens with high specificity, are essential molecules in adaptive immune system of jawed vertebrates. In this study, cDNA encoding the secreted form of the immunoglobulin heavy chain of IgM (sIgM) was cloned from the mesonephros of blunt snout bream (Megalabrama amblycephala) using RT-PCR and rapid amplification of cDNA ends (RACE). The full-length cDNA of sIgM heavy chain gene has 1961 nucleotides encoding a putative protein of 569 amino acids, constant region shares high amino acid identity with that of Ctenopharyngodon idella (80%), Carassius auratus langsdorfii (65%) and Danio rerio (59%). Multiple protein sequence alignment revealed that blunt snout bream sIgM was clustered with the homologues of cyprinid fish and constructed one clade. Using quantitative real-time PCR (qRT-PCR) analysis, the level of sIgM mRNA was determined, with a V-shape change pattern: decreased initially from unfertilized egg stage to 4 cells stage and increased from 16 cells stage to prelarva. This sharp drop indicates that sIgM mRNA is maternally transferred, and was continuously degraded until 16 cells stage. The drastic rising in sIgM level from blastula stage to prelarva might be attributed to embryonic stem cell differentiation procedure. Compared with juvenile fish, the expression of sIgM was significantly higher in pronephros, liver, spleen, gill and muscle of adult fish. After the injection of Aeromonas hydrophila, the expression pattern of sIgM was found first down-regulated at 4 h, then up-regulated and reached the peak at 7 d and 21 d in mesonephros, spleen, liver and gill, respectively.

Application of Repetitive Sequences in Fish Cell Depletion as a Target for the CRISPR/Cas9 System.

Specific cell depletion is a common means to study the physiological function of cell lineages and tissue regeneration. However, 100% depletion is difficult to achieve with existing cell depletion strategies. With the increasing maturity of CRISPR/Cas9 technology, it is increasingly used for the depletion of various cells. However, even with this technology, it is difficult to complete the depletion of specific gene knockout cells. For this reason, cell depletion with the use of repetitive sequences as the target of CRISPR/Cas9 was explored using zebrafish. All cells were used as the target cells for the first set of experiments. The results showed that injection of a mixture of DANA-gRNA and Cas9 mRNA into zygotes resulted in substantial cell apoptosis. Cells are almost invisible in the embryonic animal pole during the dome stage. The activities of the caspase-3 and caspase-9 proteins and the mRNA level of the P53 gene were significantly increased. Then, primordial germ cells (PGCs) in embryos were used as the target cells in subsequent experiments. To specifically knock out PGCs, we injected the mix of DANA-gRNA, pkop: Cas9 plasmid (the kop promotor allows Cas9 expression only in PGCs), and eGFP-nos3'UTR mRNA into zebrafish fertilized eggs. The results revealed that the activity of the caspase-3 protein was significantly increased, and the mRNA levels of P53, ku70, and ku80 were significantly upregulated, while the number of PGCs decreased gradually. Few PGCs labeled with GFP could be seen 20 h post-fertilization (hpf), and no PGCs could be seen at the germinal ridge 24 hpf. Therefore, the combination of CRISPR/Cas9 technology and repetitive sequences can achieve efficient cell depletion regardless of whether there is generalized expression or expression in specific cells. These results indicate that it is feasible to eliminate cells by using repeat sequences as CRISPR/Cas9 system target sites.

Blockchain-secure patient Digital Twin in healthcare using smart contracts.

Modern healthcare has a sharp focus on data aggregation and processing technologies. Consequently, from a data perspective, a patient may be regarded as a timestamped list of medical conditions and their corresponding corrective interventions. Technologies to securely aggregate and access data for individual patients in the quest for precision medicine have led to the adoption of Digital Twins in healthcare. Digital Twins are used in manufacturing and engineering to produce digital models of physical objects that capture the essence of device operation to enable and drive optimization. Thus, a patient's Digital Twin can significantly improve health data sharing. However, creating the Digital Twin from multiple data sources, such as the patient's electronic medical records (EMR) and personal health records (PHR) from wearable devices, presents some risks to the security of the model and the patient. The constituent data for the Digital Twin should be accessible only with permission from relevant entities and thus requires authentication, privacy, and provable provenance. This paper proposes a blockchain-secure patient Digital Twin that relies on smart contracts to automate the updating and communication processes that maintain the Digital Twin. The smart contracts govern the response the Digital Twin provides when queried, based on policies created for each patient. We highlight four research points: access control, interaction, privacy, and security of the Digital Twin and we evaluate the Digital Twin in terms of latency in the network, smart contract execution times, and data storage costs.

The Quality Evaluation of Highland Barley and Its Suitability for Chinese Traditional Tsampa Processing.

The physicochemical traits of highland barley prominently affect the quality of Tsampa. To find out the relevance between the physicochemical properties of raw material and the texture parameters of processed products, twenty-five physicochemical traits and ten quality parameters for seventy-six varieties of highland barley were measured and analyzed. The results showed that there was a significant difference between the physicochemical indexes for highland barleys of various colors. The dark highland barley generally has more fat, protein, total dietary fiber, phenolic, Mg, K, Ca, and Zn and less amylose, Fe, Cu, and Mo than light colored barley. Then, these highland barleys were made into Tsampa. A comprehensive quality evaluation model based on the color and texture parameters of Tsampa was established through principal component analysis. Then, cluster analysis was used to classify the tested samples into three edible quality grades predicated on the above evaluation model. At last, the regression analysis was applied to establish a Tsampa quality predictive model according to the physicochemical traits of the raw material. The results showed that amylose, protein, ß-Glucan, and a* and b* could be used to predict the comprehensive quality of Tsampa. The predicted results indicated that 11 of 14 validated samples were consistent with the actual quality, and the accuracy was above 78.57%. Our study built the approach of the appropriate processing varieties evaluation. It may provide reference for processing specific highland barley.

ChrII-Encoded DNA Helicase: A Preliminary Study.

BACKGROUND: DNA helicases are unwinding enzymes that are essential for many cellular processes. Research has suggested that both the model microorganisms of a single chromosome and the model microorganisms of multiple chromosomes adopt DNA helicases encoded by chromosome I. Therefore, studying DNA helicases encoded by chromosome II may lay some foundation for understanding nucleic acid metabolism processes. OBJECTIVE: To prove the existence of DNA helicase encoded by chromosome II and to reveal its difference compared to DNA helicase encoded by chromosome I. METHODS: The DNA helicases of Pseudoalteromonas spongiae JCM 12884T and Pseudoalteromonas tunicata DSM 14096T were analyzed by sequence alignment and phylogenetic relationships with other known DNA helicases. Then, proteins of P. spongiae JCM 12884T and P. tunicata DSM 14096T were obtained by heterologous expression. N-terminal sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were performed to confirm the form of proteins. A fluorescence resonance energy transfer (FRET) assay was used to measure the activity of helicases. RESULTS: DnaB-pspo and DnaB-ptun belong to the same family, the PRK08840 superfamily, and form a branch with helicases encoded by chromosome I. YwqA-pspo and YwqA-ptun have similar domains and form another branch with helicases encoded by chromosome II. All four helicases have DNA unwinding activity. YwqA is more efficient than DnaB for DNA unwinding, especially YwqA-pspo, which is encoded by bidirectional replication chromosome II. CONCLUSION: This is the first study to show that the existence of a DNA helicase encoded by chromosome II, and DNA helicase encoded by chromosome II is more efficient than chromosome I for DNA unwinding.

Investigation of a Novel Ultra-Low-Frequency Rotational Energy Harvester Based on a Double-Frequency Up-Conversion Mechanism.

Due to their lack of pollution and long replacement cycles, piezoelectric energy harvesters have gained increasing attention as emerging power generation devices. However, achieving effective energy harvesting in ultra-low-frequency (<1 Hz) rotational environments remains a challenge. Therefore, a novel rotational energy harvester (REH) with a double-frequency up-conversion mechanism was proposed in this study. It consisted of a hollow cylindrical shell with multiple piezoelectric beams and a ring-shaped slider with multiple paddles. During operation, the relative rotation between the slider and the shell induced the paddles on the slider to strike the piezoelectric beams inside the shell, thereby causing the piezoelectric beams to undergo self-excited oscillation and converting mechanical energy into electrical energy through the piezoelectric effect. Additionally, by adjusting the number of paddles and piezoelectric beams, the frequency of the piezoelectric beam struck by the paddles within one rotation cycle could be increased, further enhancing the output performance of the REH. To validate the output performance of the proposed REH, a prototype was fabricated, and the relationship between the device's output performance and parameters such as the number of paddles, system rotation speed, and device installation eccentricity was studied. The results showed that the designed REH achieved a single piezoelectric beam output power of up to 2.268 mW, while the REH with three piezoelectric beams reached an output power of 5.392 mW, with a high power density of 4.02 µW/(cm3 Hz) under a rotational excitation of 0.42 Hz, demonstrating excellent energy-harvesting characteristics.

[Effects of bosutinib on the malignant behavior of thyroid papillary carcinoma B-CPAP cells and its mechanisms].

Objective: To investigate the effects of bosutinib on the malignant behavior of thyroid papillary carcinoma B-CPAP cells and its possible mechanisms. Methods: Thyroid papillary carcinoma B-CPAP cells were cultured in vitro with a concentration gradient of(1、2、3、4 and 5 µmol/L)bosutinib intervened for 24 hours, DMSO was used as the control group. Five parallel compound holes were set in each group. Cell counting kit (CCK-8 method) method was used to detect cell proliferation. Transwell assay and cell wound healing assay were used to detect cell invasion and migration. TUNEL staining assay and flow cytometry were used to detect cell apoptosis. Western blot was used to detect the expressions of autophagic proteins (Beclin-1, LC3, p62) and signal pathway proteins (SIK2, p-mTOR, mTOR, p-ULK1, ULK1). Results: Compared with the control group, the cell proliferation activity, migration ability and invasion ability were decreased (P＜0.01), while the cell apoptosis rate was increased (P＜0.01) in the bosutinib concentration groups of 2, 3, 4 and 5 µmol/L . In the concentration groups of 4 and 5 µmol/L, the expression of Beclin-1 (P＜0.05), LC3- Ⅱ/LC3- Ⅰ (P＜0.05), SIK2 (P＜0.01) and p-ULK1 (P＜0.01) protein was decreased, while the expression of p62 (P＜ 0.05) and p-mTOR (P＜0.01) protein was increased. Conclusion: Bosutinib may inhibit the autophagy of thyroid papillary carcinoma cells through SIK2-mTOR-ULK1 signaling pathway to inhibit their proliferation, invasion and migration and promote apoptosis, thereby weakening their malignant behavior.

Smp24, a Scorpion-Venom Peptide, Exhibits Potent Antitumor Effects against Hepatoma HepG2 Cells via Multi-Mechanisms In Vivo and In Vitro.

Scorpion-venom-derived peptides have become a promising anticancer agent due to their cytotoxicity against tumor cells via multiple mechanisms. The suppressive effect of the cationic antimicrobial peptide Smp24, which is derived from the venom of Scorpio Maurus palmatus, on the proliferation of the hepatoma cell line HepG2 has been reported earlier. However, its mode of action against HepG2 hepatoma cells remains unclear. In the current research, Smp24 was discovered to suppress the viability of HepG2 cells while having a minor effect on normal LO2 cells. Moreover, endocytosis and pore formation were demonstrated to be involved in the uptake of Smp24 into HepG2 cells, which subsequently interacted with the mitochondrial membrane and caused the decrease in its potential, cytoskeleton reorganization, ROS accumulation, mitochondrial dysfunction, and alteration of apoptosis- and autophagy-related signaling pathways. The protecting activity of Smp24 in the HepG2 xenograft mice model was also demonstrated. Therefore, our data suggest that the antitumor effect of Smp24 is closely related to the induction of cell apoptosis, cycle arrest, and autophagy via cell membrane disruption and mitochondrial dysfunction, suggesting a potential alternative in hepatocellular carcinoma treatment.