Neural Network Circuits for Bionic Associative Memory and Temporal Order Memory Based on DNA Strand Displacement.

Pavlovian associative memory plays an important role in our daily life and work. The realization of Pavlovian associative memory at the deoxyribonucleic acid (DNA) molecular level will promote the development of biological computing and broaden the application scenarios of neural networks. In this article, bionic associative memory and temporal order memory circuits are constructed by DNA strand displacement (DSD) reactions. First, a temporal logic gate is constructed on the basis of DSD circuit and extended to a three-input temporal logic gate. The output of temporal logic gate is used for the weight species of associative memory. Second, the forgetting module and output module based on the DSD circuit are constructed to realize some functions of associative memory, including associative memory with simultaneous stimulus, associative memory with interstimulus interval effect, and the facilitation by intermittent stimulus. In addition, the coding, storage, and retrieval modules are designed based on the analysis and memory capabilities of temporal logic gate for temporal information. The temporal order memory circuit is constructed, demonstrating the temporal order memory ability of DNA circuit. Finally, the reliability of the circuit is verified through Visual DSD software simulation. Our work provides ideas and inspiration to construct more complex DNA bionic circuits and intelligent circuits by using DSD technology.

Enhancing the catalytic efficiency of M32 carboxypeptidase by semi-rational design and its applications in food taste improvement.

BACKGROUND: Carboxypeptidase is an exopeptidase that hydrolyzes amino acids at the C-terminal end of the peptide chain and has a wide range of applications in food. However, in industrial applications, the relatively low catalytic efficiency of carboxypeptidases is one of the main limiting factors for industrialization. RESULTS: The study has enhanced the catalytic efficiency of Bacillus megaterium M32 carboxypeptidase (BmeCPM32) through semi-rational design. Firstly, the specific activity of the optimal mutant, BmeCPM32-M2, obtained through single-site mutagenesis and combinatorial mutagenesis, was 2.2-fold higher than that of the wild type (187.9 versus 417.8 U mg-1), and the catalytic efficiency was 2.9-fold higher (110.14 versus 325.75 s-1 mmol-1). Secondly, compared to the wild type, BmeCPM32-M2 exhibited a 1.8-fold increase in half-life at 60 °C, with no significant changes in its enzymatic properties (optimal pH, optimal temperature). Finally, BmeCPM32-M2 significantly increased the umami intensity of soy protein isolate hydrolysate by 55% and reduced bitterness by 83%, indicating its potential in developing tasty protein components. CONCLUSION: Our research has revealed that the strategy based on protein sequence evolution and computational residue mutation energy led to an improved catalytic efficiency of BmeCPM32. Molecular dynamics simulations have revealed that a smaller substrate binding pocket and increased enzyme-substrate affinity are the reasons for the enhanced catalytic efficiency. Furthermore the number of hydrogen bonds and solvent and surface area may contribute to the improvement of thermostability. Finally, the de-bittering effect of BmeCPM32-M2 in soy protein isolate hydrolysate suggests its potential in developing palatable protein components. © 2024 Society of Chemical Industry.

Interplay of Ferroptosis and Cuproptosis in Cancer: Dissecting Metal-Driven Mechanisms for Therapeutic Potentials.

Iron (Fe) and copper (Cu), essential transition metals, play pivotal roles in various cellular processes critical to cancer biology, including cell proliferation, mitochondrial respiration, distant metastases, and oxidative stress. The emergence of ferroptosis and cuproptosis as distinct forms of non-apoptotic cell death has heightened their significance, particularly in connection with these metal ions. While initially studied separately, recent evidence underscores the interdependence of ferroptosis and cuproptosis. Studies reveal a link between mitochondrial copper accumulation and ferroptosis induction. This interconnected relationship presents a promising strategy, especially for addressing refractory cancers marked by drug tolerance. Harnessing the toxicity of iron and copper in clinical settings becomes crucial. Simultaneous targeting of ferroptosis and cuproptosis, exemplified by the combination of sorafenib and elesclomol-Cu, represents an intriguing approach. Strategies targeting mitochondria further enhance the precision of these approaches, providing hope for improving treatment outcomes of drug-resistant cancers. Moreover, the combination of iron chelators and copper-lowering agents with established therapeutic modalities exhibits a synergy that holds promise for the augmentation of anti-tumor efficacy in various malignancies. This review elaborates on the complex interplay between ferroptosis and cuproptosis, including their underlying mechanisms, and explores their potential as druggable targets in both cancer research and clinical settings.

Towards virtual machine scheduling research based on multi-decision AHP method in the cloud computing platform.

Virtual machine scheduling and resource allocation mechanism in the process of dynamic virtual machine consolidation is a promising access to alleviate the cloud data centers of prominent energy consumption and service level agreement violations with improvement in quality of service (QoS). In this article, we propose an efficient algorithm (AESVMP) based on the Analytic Hierarchy Process (AHP) for the virtual machine scheduling in accordance with the measure. Firstly, we take into consideration three key criteria including the host of power consumption, available resource and resource allocation balance ratio, in which the ratio can be calculated by the balance value between overall three-dimensional resource (CPU, RAM, BW) flat surface and resource allocation flat surface (when new migrated virtual machine (VM) consumed the targeted host's resource). Then, virtual machine placement decision is determined by the application of multi-criteria decision making techniques AHP embedded with the above-mentioned three criteria. Extensive experimental results based on the CloudSim emulator using 10 PlanetLab workloads demonstrate that the proposed approach can reduce the cloud data center of number of migration, service level agreement violation (SLAV), aggregate indicators of energy comsumption (ESV) by an average of 51.76%, 67.4%, 67.6% compared with the cutting-edge method LBVMP, which validates the effectiveness.

A novel damage identification method for flue gas turbine blades based on tip timing.

Tip timing signal analysis has been applied to the online condition monitoring of high-speed blades. However, traditional tip timing analysis methods are not suitable for low-speed flue gas turbines. Therefore, this paper proposes a novel blade tip timing signal analysis method based on an investigation of the dynamic response characteristics of low-speed blades. First, the finite element modal theory is introduced to analyze the characteristics of blade damage. Second, an equivalent cantilever beam analysis model of flue gas turbine blades is established under complex environment and working conditions. In order to monitor the variation of local stiffness, a damage identification method based on the variation of the free end deflection of the equivalent cantilever beam is proposed. Finally, a rotating blade tip timing monitoring testing rig is established to verify the feasibility of the proposed method. The results show that the cracks originating at about 80% of the blade height have the greatest influence on blade stiffness, followed by blade root. The calculated blade damage parameters are 4.8464 mm and 3.7588 mm, and the crack influencing factors are 4.7476 and 3.6822, respectively, indicating that the change trend is consistent with the blade damage rules.

i-CRISPR: a personalized cancer therapy strategy through cutting cancer-specific mutations.

Developing a strategy to specifically kill cancer cells without inducing obvious damage to normal cells may be of great clinical significance for cancer treatment. In the present study, we developed a new precise personalized strategy named "i-CRISPR" for cancer treatment through adding DNA damage repair inhibitors(i) and inducing cancer cell-specific DNA double strand breaks by CRISPR. Through in vitro and in vivo experiments, we confirmed the efficacy of this strategy in multiple cancer models and revealed the mechanism of cell death. Our strategy might provide a novel concept for precise cancer therapy.

First case report of complete paternal isodisomy of chromosome 10 harbouring a novel variant in COL17A1 that causes junctional epidermolysis bullosa intermediate.

BACKGROUND: Uniparental disomy (UPD) is a condition in which both chromosomes are inherited from the same parent, except for imprinting disorders. Uniparental isodisomy (UPiD) may result in a homozygous variant contributing to an autosomal recessive disorder in the offspring of a heterozygous carrier. Junctional epidermolysis bullosa intermediate (JEB intermediate) is an autosomal recessive inherited disease that is associated with a series of gene variants, including those of COL17A1. CASE PRESENTATION: We report the first case of complete paternal UPiD of chromosome 10 harbouring a novel homozygous variant in COL17A1: c.1880(exon23)delG (p.G627Afs*56). This variant led to the clinical phenotype of junctional epidermolysis bullosa intermediate in a 5-year-old child. Trio-whole exome sequencing (Trio-WES) and in silico data analysis were used for variant identification, Sanger sequencing was performed for variant validation, and pathological examination was performed as the gold standard for phenotype confirmation. CONCLUSIONS: We recommend the use of WES as a first-tier test for the diagnosis of epidermolysis bullosa, especially for paediatric patients. Moreover, UPD events should be detected and analysed routinely through WES data in the future.

Circular RNA circ_0008934 promotes hepatocellular carcinoma growth and metastasis through modulating miR-1305/TMTC3 axis.

Circular RNAs (circRNAs) play important roles in the progression of hepatocellular carcinoma (HCC). However, the exact function of circ_0008934 in HCC is unknown. Our study aimed to investigate the expression characteristics of circ_0008934 in HCC and its effects on the proliferation and metastasis of HCC, and to explore the potential mechanism. In this study, circ_0008934 expression was found to be significantly upregulated in HCC tissues and cell lines by qRT-PCR. High level of circ_0008934 is closely associated with higher serum AFP (P < 0.001), larger tumor diameter (P = 0.012), microvascular invasion (P = 0.008) and poorer prognosis (P = 0.007) of HCC patients. Functionally, knockdown of circ_0008934 inhibited HCC cell proliferation, invasion and migration in vitro and vivo. Mechanically, circ_0008934 was a sponge of miR-1305 to facilitate the TMTC3 expression, and the TMTC3 expression in HCC tissues was negatively associated with the survival of HCC patients. Furthermore, rescued assays revealed that the circ_0008934 facilitated HCC proliferation, invasion and migration by regulating miR-1305/ TMTC3 signaling pathways. Overall, these results demonstrate that downregulation of circ_0008934 repress HCC growth and metastasis by upregulating miR-1305 to inhibit TMTC3, suggesting circ_0008934/ miR-1305/ TMTC3 regulatory axis may be a possible novel therapeutic target for HCC.

Optimal stimulation frequency for vibrational optical coherence elastography.

Vibrational optical coherence elastography (OCE) is a promising tool for extracting the mechanical property of soft tissue. Purpose of this study is focusing on settling the optimal frequency range for vibrational OCE with evenly distributed stress filed. A finite element model of 2% agar phantom was built by ANSYS with a vibration stimulation frequency range from 200 to 3000 Hz. Practical experiments were carried out for cross-validation with the same frequencies and sample. Lateral and horizontal stress filed distributions under different frequencies were mathematically evaluated by coefficient of variance and degree of linearity. Results from simulation and practical experiment cross-validated each other and 1000 Hz was set as the maximum ideal frequency for vibrational OCE, while the minimum frequency is set by theoretical calculation with a result of 250 Hz. An ex vivo biological sample was utilised to testify performance of vibrational OCE with excitation frequencies in and out of concluded optimal range, which showed that stiffness was better mapped out in optimal frequency range.

Isolation and identification of EST-SSR markers in Ixonanthes chinensis (Ixonanthaceae).

PREMISE: Ixonanthes (Ixonanthaceae) consists of between three and 19 species, among which I. chinensis and I. khasiana are considered vulnerable. Here, 58 microsatellite markers were developed for further conservation of these two Ixonanthes species. METHODS AND RESULTS: RNA transcripts of I. chinensis were sequenced and assembled into 19,545 unigenes, and 994 simple sequence repeat (SSR) loci were identified from 920 contigs. Based on these, 106 primer pairs were designed, 58 were successfully amplified, and 12 demonstrated polymorphism among five populations. The number of alleles per locus varied from three to 10, and the levels of observed and expected heterozygosity ranged from 0.000 to 1.000 and 0.000 to 0.844, respectively. Further assessment of the transferability of the 58 amplifiable primers reported 30 being successfully cross-amplified in I. icosandra and three in Erythroxylum sinense. CONCLUSIONS: These novel SSR markers will be useful for future genetic conservation studies on these Ixonanthes species.

HBx-related long non-coding RNA 01152 promotes cell proliferation and survival by IL-23 in hepatocellular carcinoma.

Accumulating evidence suggests that long-noncoding RNA (lncRNA) plays important roles in hepatitis B virus (HBV) infections. However, the mechanism underlying how lncRNA regulate hepatocellular carcinoma process remains largely unknown. In this study we found that the expression of LINC01152 was significantly increased in HBV positive HCC tissues and cells and was induced by HBx in vitro. The overexpression of LINC01152 could increases HCC cell proliferation and promotes tumor formation in nude mice. Mechanistically, HBx could increase the transcription of LINC01152. Elevated LINC01152 binds to the promoter region of IL-23, promoting its transcriptional activity and upregulating the levels of Stat3 and p-Stat3. Our findings suggest that LINC01152 plays an important role in HBV-related hepatocellular carcinoma development and may serve as a therapeutic marker for hepatocellular carcinoma.

Learning to Monitor Machine Health with Convolutional Bi-Directional LSTM Networks.

In modern manufacturing systems and industries, more and more research efforts have been made in developing effective machine health monitoring systems. Among various machine health monitoring approaches, data-driven methods are gaining in popularity due to the development of advanced sensing and data analytic techniques. However, considering the noise, varying length and irregular sampling behind sensory data, this kind of sequential data cannot be fed into classification and regression models directly. Therefore, previous work focuses on feature extraction/fusion methods requiring expensive human labor and high quality expert knowledge. With the development of deep learning methods in the last few years, which redefine representation learning from raw data, a deep neural network structure named Convolutional Bi-directional Long Short-Term Memory networks (CBLSTM) has been designed here to address raw sensory data. CBLSTM firstly uses CNN to extract local features that are robust and informative from the sequential input. Then, bi-directional LSTM is introduced to encode temporal information. Long Short-Term Memory networks(LSTMs) are able to capture long-term dependencies and model sequential data, and the bi-directional structure enables the capture of past and future contexts. Stacked, fully-connected layers and the linear regression layer are built on top of bi-directional LSTMs to predict the target value. Here, a real-life tool wear test is introduced, and our proposed CBLSTM is able to predict the actual tool wear based on raw sensory data. The experimental results have shown that our model is able to outperform several state-of-the-art baseline methods.

Skeleton extraction and phase interpolation for single ESPI fringe pattern based on the partial differential equations.

A novel phase extraction method for single electronic speckle pattern interferometry (ESPI) fringes is proposed. The partial differential equations (PDEs) are used to extract the skeletons of the gray-scale fringe and to interpolate the whole-field phase values based on skeleton map. Firstly, the gradient vector field (GVF) of the initial fringe is adjusted by an anisotropic PDE. Secondly, the skeletons of the fringe are extracted combining the divergence property of the adjusted GVF. After assigning skeleton orders, the whole-field phase information is interpolated by the heat conduction equation. The validity of the proposed method is verified by computer-simulated and experimentally obtained poor-quality ESPI fringe patterns.

[Differential expression in ACE2, Ang(1-7) and Mas receptor during progression of liver fibrosis in a rat model].

OBJECTIVE: To investigate the changes in expression of the ACE2/Ang(1-7)/Mas receptor axis' components that occur during progression of liver fibrosis using a rat model system. METHODS: Thirty-six adult male Wistar rats, were randomly assigned to groups of normal control (n = 6; no manipulation) and liver fibrosis (n = 30; given a subcutaneous injection of 40% chronic carbon tetrachloride (CCl4)). At post-injection days 15, 30, 45, 60 and 75, 1 control rat and 6 modeled rats were sacrificed for analysis. Histopathological analysis of liver tissue was performed with hematoxylin-eosin and rapid Masson staining. Protein expression level of Ang(1-7) was determined by enzyme-linked immunosorbent assay, and of ACE2 and Mas receptor was evaluated by immunohistochemistry. Real-time PCR was used to measure the mRNA expression levels of ACE2 and Mas receptor. RESULTS: The expression levels of ACE2, Ang(1-7) and Mas receptor showed a statistically significant upward trend that followed the progression of fibrosis up to post-injection day 60 (P less than 0.01), but the significant increase was not seen from day 60 to day 75. CONCLUSION: Each component of the ACE2/Ang(1-7)/Mas receptor axis shows differential expression during the development of liver fibrosis and may contribute to disease progression.

Anisotropic coupled diffusion filter and binarization for the electronic speckle pattern interferometry fringes.

In this paper novel approaches based on anisotropic coupled diffusion equations are presented to do filter and binarization for ESPI fringes. An advantageous characteristic associated with the proposed technique is that diffusion takes place mainly along the direction of the edge. Therefore, the proposed anisotropic coupled diffusion filter method can avoid blur of the fringe edge and protect the useful information of the fringe patterns. The anisotropic coupled diffusion binarization, which can repair the image boundary anisotropically, is able to avoid the redundant burr. More important, it can be directly applied to the noisy ESPI fringe patterns without much preprocessing, which is a significant advance in fringe analysis for ESPI. The effective of the proposed methods are tested by means of the computer-simulated and experimentally obtained fringe patterns, respectively.

[Studies on the chemical constituents from aerial parts of Gynura divaricata].

OBJECTIVE: To study the chemical constituents from aerial parts of Gynura divaricata. METHODS: The constituents were isolated on silica gel column chromatography, preparative TLC and Sephadex LH-20 column chromatography, identified by physicochemical properties and the structures were elucidated by spectral analysis. RESULTS: 10 compounds were isolated and identified as 2-(1', 2', 3', 4'-tetrahydroxybutyl)-6-(2", 3", 4"-trihydroxybutyl)-pyrazine (1), 2-(1', 2', 3', 4'-tetrahydroxybutyl)-5-(2", 3", 4"-trihydroxybutyl) -pyrazine (2), nicotinic acid (3), 5-hydroxy-picolinic acid(4), methyl-5-hydroxy-2- pyridinecarboxylate (5), adenosine (6), uridine (7), stigmasterol-5-O- beta-D-glucoside (8), dibutyl terephthalate (9), methyl chlorogenate (10). CONCLUSION: Compounds 1, 2, 5, 9, 10 are obtained from this genus for the first time, Compounds 3, 4 are obtained from this plant for the first time.

[Protecting effect of Chaenomeles speciosa broth on immunosuppressive mice induced by cyclophosphamide].

OBJECTIVE: To investigate the effects of Chaenomeles speciosa broth on immunoregulation for anti-tumor chemotherapy. METHODS: Immunosuppressive model was induced by cyclophosphamide (CTX) in mice. The mice were treated with the broth for 15 days. The serum hemolysin was observed in mouse sera. Spleen lymphocyte transformation and gene transcription related to the immunoregulation in spleen lymphocytes were detected. RESULTS: After administrated the broth, the serum hemolysin and lymphocyte transformation rates significantly increased and the mRNA expression of foxp3, TGF-beta, PD1, Fas, Bax were downregulated compared with CTX-group. CONCLUSION: Chaenomeles speciosa broth has protective effects on the immunosuppressive mouse induce by CTX.

A new cerebroside from Gynura divaricata.

A new cerebroside (1) was isolated from the aerial parts of Gynura divaricata DC., along with five known compounds: kaempferol (2), kaempferol 3-O-glucoside (3), kaempferol 3-O-rhamnosyl(1 --> 6)glucoside (4), beta-sitosteryl glucoside-6'-O-heptadecoicate (5) and 2-(1', 2', 3', 4'-tetrahydroxybutyl)-6-(2'', 3'', 4''-trihydroxybutyl)-pyrazine (6), which are isolated for the first time from this species. The structure of 1 was determined to be 1-O-beta-D-glucopyranosyl-(2S, 3S, 4R, 10Z)-2-[(2'R)-2'-hydroxylignocenoyl-amino]-10-octadecene-1,3,4-triol on the basis of chemical and spectroscopic evidence.