The role of hematological parameters in asymptomatic and non-severe cases of Omicron variant infection.

BACKGROUND: Omicron variants are currently the predominant circulating lineage worldwide and most cases are mild or asymptomatic. The Omicron variant is characterized by high transmissibility and immune evasion. Early identification of Omicron cases in clinical settings is crucial for controlling its spread. Previous studies have indicated that changes in hematological parameters can be used to predict the severity of coronavirus disease 2019 (COVID-19). However, the role of hematological parameters in non-severe and asymptomatic cases remains unknown. This study aimed to investigate the role of hematological parameters in non-severe and asymptomatic Omicron variant infections. METHODS: Hematological parameters and results were analyzed and compared in symptomatic (n = 356) and asymptomatic (n = 171) groups respectively, and between these two groups with positive COVID-19 tests. The utility of hematological parameters for predicting positive COVID-19 tests was analyzed using receiver operating characteristic curves. RESULTS: Individuals with non-severe cases exhibited decreased levels of platelets, lymphocytes, eosinophils, basophils, lymphocytes (%), eosinophils (%), and basophils (%), while exhibiting elevated counts of monocytes, neutrophils (%), monocytes (%), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) when compared to suspected cases or asymptomatic carriers. In asymptomatic patients, positive carriers had lower leukocyte, neutrophil, and lymphocyte counts but higher monocyte, monocyte (%), PLR, and CRP levels than negative carriers. Basophil counts combined with lymphocytes or the PLR demonstrated a more significant predictive value in screening non-severe cases earlier compared to other parameters. The combined assessment of the monocyte (%) and the PLR had the highest area under the curve for diagnosing asymptomatic carriers. CONCLUSIONS: Circulating basophils, alone or in combination with other hematological parameters, may be used as efficient biomarkers for early screening of non-severe Omicron cases.

Evolutionary Multiobjective Molecule Optimization in an Implicit Chemical Space.

Optimization techniques play a pivotal role in advancing drug development, serving as the foundation of numerous generative methods tailored to efficiently design optimized molecules derived from existing lead compounds. However, existing methods often encounter difficulties in generating diverse, novel, and high-property molecules that simultaneously optimize multiple drug properties. To overcome this bottleneck, we propose a multiobjective molecule optimization framework (MOMO). MOMO employs a specially designed Pareto-based multiproperty evaluation strategy at the molecular sequence level to guide the evolutionary search in an implicit chemical space. A comparative analysis of MOMO with five state-of-the-art methods across two benchmark multiproperty molecule optimization tasks reveals that MOMO markedly outperforms them in terms of diversity, novelty, and optimized properties. The practical applicability of MOMO in drug discovery has also been validated on four challenging tasks in the real-world discovery problem. These results suggest that MOMO can provide a useful tool to facilitate molecule optimization problems with multiple properties.

Biosynthesis of eriodictyol in citrus waster by endowing P450BM3 activity of naringenin hydroxylation.

The flavonoid naringenin is abundantly present in pomelo peels, and the unprocessed naringenin in wastes is not friendly for the environment once discarded directly. Fortunately, the hydroxylated product of eriodictyol from naringenin exhibits remarkable antioxidant and anticancer properties. The P450s was suggested promising for the bioconversion of the flavonoids, but less naturally existed P450s show hydroxylation activity to C3' of the naringenin. By well analyzing the catalytic mechanism and the conformations of the naringenin in P450, we proposed that the intermediate Cmpd I ((porphyrin)Fe = O) is more reasonable as key conformation for the hydrolyzation, and the distance between C3'/C5' of naringenin to the O atom of CmpdI determines the hydroxylating activity for the naringenin. Thus, the "flying kite model" that gradually drags the C-H bond of the substrate to the O atom of CmpdI was put forward for rational design. With ab initio design, we successfully endowed the self-sufficient P450-BM3 hydroxylic activity to naringenin and obtained mutant M5-5, with kcat, Km, and kcat/Km values of 230.45 min-1, 310.48 µM, and 0.742 min-1 µM-1, respectively. Furthermore, the mutant M4186 was screened with kcat/Km of 4.28-fold highly improved than the reported M13. The M4186 also exhibited 62.57% yield of eriodictyol, more suitable for the industrial application. This study provided a theoretical guide for the rational design of P450s to the nonnative compounds. KEY POINTS: •The compound I is proposed as the starting point for the rational design of the P450BM3 •"Flying kite model" is proposed based on the distance between O of Cmpd I and C3'/C5' of naringenin •Mutant M15-5 with 1.6-fold of activity than M13 was obtained by ab initio modification.

Protein intrinsically disordered region prediction by combining neural architecture search and multi-objective genetic algorithm.

BACKGROUND: Intrinsically disordered regions (IDRs) are widely distributed in proteins and related to many important biological functions. Accurately identifying IDRs is of great significance for protein structure and function analysis. Because the long disordered regions (LDRs) and short disordered regions (SDRs) share different characteristics, the existing predictors fail to achieve better and more stable performance on datasets with different ratios between LDRs and SDRs. There are two main reasons. First, the existing predictors construct network structures based on their own experiences such as convolutional neural network (CNN) which is used to extract the feature of neighboring residues in protein, and long short-term memory (LSTM) is used to extract the long-distance dependencies feature of protein residues. But these networks cannot capture the hidden feature associated with the length-dependent between residues. Second, many algorithms based on deep learning have been proposed but the complementarity of the existing predictors is not fully explored and used. RESULTS: In this study, the neural architecture search (NAS) algorithm was employed to automatically construct the network structures so as to capture the hidden features in protein sequences. In order to stably predict both the LDRs and SDRs, the model constructed by NAS was combined with length-dependent models for capturing the unique features of SDRs or LDRs and general models for capturing the common features between LDRs and SDRs. A new predictor called IDP-Fusion was proposed. CONCLUSIONS: Experimental results showed that IDP-Fusion can achieve more stable performance than the other existing predictors on independent test sets with different ratios between SDRs and LDRs.

The 'Ironclad friendship' of China-Cambodia, lays the first step in the foundation of early diagnosis and treatment of asymptomatic congenital heart Defects- A multi-national screening and intervention project, 2017-2020.

BACKGROUND: Congenital heart disease (CHD) is the leading cause of mortality in childhood worldwide. However, a large number of children with CHD are not diagnosed promptly in low- and middle-income regions, due to limited healthcare resources and lack the ability of prenatal and postnatal ultrasound examinations. The research on asymptomatic CHD in the community is still blank, resulting in a large number of children with asymptomatic CHD can not be found and treated in time. Through the China-Cambodia collaborative health care initiative, the project team conducted research, screened children's CHD through a sampling survey in China and Cambodia, collected relevant data, and retrospectively analyzed the data of all eligible patients. OBJECTIVES: The project aimed to evaluate the prevalence of asymptomatic CHD in a sample population of 3-18years old and effects on their growth status and treatment outcomes. METHODS: We examined the prevalence of 'asymptomatic CHD' among 3-18years old children and adolescents at the township/county levels in the two participating. A total of eight provinces in China and five provinces in Cambodia were analyzed from 2017 to 2020. During 1 year follow-up after treatment, the differences in heights and weights of the treated and control groups were evaluated. RESULTS: Among the 3,068,075 participants screened from 2017 to 2020, 3967 patients with asymptomatic CHD requiring treatment were identified [0.130%, 95% confidence interval (CI) 0.126 -0.134%]. The prevalence rate of CHD ranged from 0.02 to 0.88%, and was negatively related to local per capita GDP (p = 0.028). The average height of 3310 treated CHD patients were 2.23% (95% CI: -2.51%~-1.9%) lower than that of the standard group and the average weight was - 6.41% (95% CI: -7.17%~-5.65%) lower, the developmental gap widening with advancing age. One year after treatment, the relative height difference remained comparable while that, in weight was reduced by 5.68% (95% CI: 4.27% ~7.09%). CONCLUSIONS: Asymptomatic CHD now is often overlooked and is an emerging public health challenge. Early detection and treatment are essential to lower the potential burden of heart diseases in children and adolescents.

Development of information integration in the visual working memory of preschoolers.

Visual working memory (WM) plays a pivotal role in integrating fragments into meaningful units, but no study has addressed how visual WM integration takes place in children. The current study examined whether WM integration emerges once preschoolers master Gestalt cue and can retain two representations in WM (automatic integration hypothesis), or still needs time to mature (maturation-of-integration hypothesis). Four experiments (N = 168, 81 females, 4- to 6-year-olds, Chinese, in Hangzhou, China, from 2016.10 to 2021.11) were conducted. Although 4-year-olds can retain two objects in WM and benefit from Gestalt cues in simultaneous display (Cohen's ds >1.00), they failed when memory arrays were presented sequentially. Meanwhile, 5- and 6-year-olds consistently demonstrated WM integration ability (all Cohen's ds >0.69), supporting the maturation-of-integration hypothesis.

Healthy lifestyle behaviours and all-cause and cardiovascular mortality among 0.9 million Chinese adults.

BACKGROUND: Healthy lifestyle behaviours are effective means to reduce the burden of diseases. This study was aimed to fill the knowledge gaps on the distribution, associated factors, and potential health benefits on mortality of four healthy lifestyle behaviours in China. METHODS: During 2015-2019, participants aged 35-75 years from 31 provinces were recruited by the China PEACE Million Persons Project. Four healthy lifestyle behaviours were investigated in our study, including non-smoking, none or moderate alcohol use, sufficient leisure time physical activity (LTPA), and healthy diet. RESULTS: Among 903,499 participants, 74.1% were non-smokers, 96.0% had none or moderate alcohol use, 23.6% had sufficient LTPA, 11.1% had healthy diet, and only 2.8% had all the four healthy lifestyle behaviours. The adherence varied across seven regions; the highest median of county-level adherence to all the four healthy lifestyle behaviours was in North China (3.3%) while the lowest in the Southwest (0.8%) (p < 0.05). Participants who were female, elder, non-farmers, urban residents, with higher income or education, hypertensive or diabetic, or with a cardiovascular disease (CVD) history were more likely to adhere to all the four healthy lifestyle behaviours (p < 0.001). County-level per capital Gross Domestic Product (GDP) was positively associated with sufficient LTPA (p < 0.05 for both rural and urban areas) and healthy diet (p < 0.01 for urban areas), while negatively associated with none or moderate alcohol use (p < 0.01 for rural areas). Average annual temperature was negatively associated with none or moderate alcohol use (p < 0.05 for rural areas) and healthy diet (p < 0.001 for rural areas). Those adhering to all the four healthy lifestyle behaviours had lower risks of all-cause mortality (HR 0.64 [95% CI: 0.52, 0.79]) and cardiovascular mortality (HR 0.53 [0.37, 0.76]) after a median follow-up of 2.4 years. CONCLUSIONS: Adherence to healthy lifestyle behaviours in China was far from ideal. Targeted health promotion strategies were urgently needed.

PIM1 inhibition attenuated endotoxin-induced acute lung injury through modulating ELK3/ICAM1 axis on pulmonary microvascular endothelial cells.

OBJECTIVE: The dysfunction of pulmonary microvascular endothelial cells (PMVECs) is one of the critical characteristics of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) induced by severe infection. PIM1 is a constitutively active serine/threonine kinase that is involved in multiple biological processes. However, the underlying correlation between PIM1 and PMVECs injury remains unclear. The main purpose of this study was to reveal roles of PIM1 and explore the potential mechanisms during the development of endotoxin-induced ALI induced by intraperitoneal LPS administration. MATERIALS AND METHODS: PIM1 level in the lung tissues of endotoxin-induced ALI mice or plasma derived from cardiopulmonary bypass (CPB)-induced ALI patients were measured. The protective roles of PIM1 specific inhibitor SMI-4a on endotoxin-induced lung injuries were evaluated through histological, permeability, neutrophil infiltration and survival assessment. The relationship between PIM1 and ELK3/ICAM-1 axis was validated in vivo and vitro. The correlation between plasma PIM1 and indicative vascular endothelium injury biomarkers (PaO2/FiO2 ratio, Ang-II, E-selectin and PAI-1) levels derived from CPB-induced ALI patient were analyzed. RESULTS: PIM1 expression in the lung tissues was increased in the mice of endotoxin-induced ALI. The PIM1 specific inhibitor SMI-4a administration relieved the severity of endotoxin-induced ALI. More importantly, PIM1 modulates ICAM1 expression through regulating transcription factor ELK3 expression in vitro. Eventually, plasma PIM1 level was positively correlated with Ang-II and PAI-1 levels but negatively correlated with SpO2/FiO2 ratio among CPB induced ALI patients. CONCLUSION: Our results indicated that PIM1 inhibition carried a protective role against endotoxin-induced ALI by modulating the ELK3/ICAM1 axis on PMVECs. PIM1 may be a potential therapeutic target for endotoxin-induced ALI.

A unified method of detecting core-periphery structure and community structure in networks.

The core-periphery structure and the community structure are two typical meso-scale structures in complex networks. Although community detection has been extensively investigated from different perspectives, the definition and the detection of the core-periphery structure have not received much attention. Furthermore, the detection problems of the core-periphery and community structure were separately investigated. In this paper, we develop a unified framework to simultaneously detect the core-periphery structure and community structure in complex networks. Moreover, there are several extra advantages of our algorithm: our method can detect not only single but also multiple pairs of core-periphery structures; the overlapping nodes belonging to different communities can be identified; different scales of core-periphery structures can be detected by adjusting the size of the core. The good performance of the method has been validated on synthetic and real complex networks. So, we provide a basic framework to detect the two typical meso-scale structures: the core-periphery structure and the community structure.

Participation of Antidiuretic Hormone (ADH) in Asthma Exacerbations Induced by Psychological Stress via PKA/PKC Signal Pathway in Airway-Related Vagal Preganglionic Neurons (AVPNs).

AIMS: Present study was performed to examine whether ADH was implicated in psychological stress asthma and to explore the underlying molecular mechanism. METHODS: We not only examined ADH levels in the cerebrospinal fluid (CSF) via radioimmunoassay, but also measured ADH receptor (ADHR) expression in airway-related vagal preganglionic neurons (AVPNs) through real-time PCR in all experimental mice. Western blotting was performed to evaluate the relationship between ADH and PKA/PKC in psychological stress asthma. Finally, the role of PKA/PKC in psychological stress asthma was analyzed. RESULTS: Marked asthma exacerbations were noted owing to significantly elevated levels of ADH and ADHR after psychological stress induction as compared to OVA alone (asthma group). ADHR antagonists (SR-49095 or SR-121463A) dramatically lowered higher protein levels of PKAα and PKCα induced by psychological stress as compared to OVA alone, suggesting the correlation between ADH and PKA/PKC in psychological stress asthma. KT-5720 (PKA inhibitor) and Go-7874 (PKC inhibitor) further directly revealed the involvement of PKA/PKC in psychological stress asthma. Some notable changes were also noted after employing PKA and PKC inhibitors in psychological stress asthma, including reduced asthmatic inflammation (lower eosinophil peroxidase (EPO) activity, myeloperoxidase (MPO) activity, immunoglobulin E (IgE) level, and histamine release), substantial decrements in inflammatory cell counts (eosinophils and lymphocytes), and decreased cytokine secretion (IL-6, IL-10, and IFN-γ), indicating the involvement of PKA/PKC in asthma exacerbations induced by psychological stress. CONCLUSION: Our results strongly suggested that ADH participated in psychological stress-induced asthma exacerbations via PKA/PKC signal pathway in AVPNs.

CD24 is a genetic modifier for risk and progression of prostate cancer.

CD24 plays an oncogenic role in the onset and progression of various human cancers, including prostate cancer. In the present study, we identified two linkage disequilibrium blocks with four recombination hotspot motifs in human CD24 locus. To elucidate whether genetic variants of CD24 are associated with susceptibility to prostate cancer and its disease status, we conducted a case-control association study with two P170 C/T and P-534 A/C polymorphisms of CD24 in 590 patients with prostate cancer and 590 healthy controls. A significant increased risk of prostate cancer was found in men with the P170T/T genotype over the P170C/C genotype (odd ratio = 1.74, 95% confidence interval = 1.16-2.63, P = 0.008), and in men with the P-534C/C genotype over the P-534A/A genotype (odd ratio = 1.47, 95% CI = 1.18-2.26, P = 0.003). Cochran-Armitage trend analysis showed that the P170T allele was significantly correlated with an increased risk of prostate cancer progression (P = 0.029, trend between genotypes and stages) and this observation was also validated in an independent sample cohort. Next, we found that tumors with P170T or P-534C alleles had more twofold increased protein expressions of CD24 as compared to those with P170C or P-534A alleles, respectively. Likewise, tumors with a combination of P170T/T and P-534C/C genotypes were associated with a high mRNA level of CD24. Our data suggest a significant association of CD24 genetic variants with prostate cancer onset and progression, which provides new insight into molecular genetics of prostate cancer; however, these findings need to be validated in multiple independent cohorts. © 2016 Wiley Periodicals, Inc.

Sevoflurane prevents stroke-induced depressive and anxiety behaviors by promoting cannabinoid receptor subtype I-dependent interaction between ß-arrestin 2 and extracellular signal-regulated kinases 1/2 in the rat hippocampus.

One of the most frequent psychological consequences of stroke is depression. Previous animal studies have demonstrated that post-conditioning with sevoflurane protects against focal cerebral ischemia and reperfusion injury. Thus, we hypothesized that repeated exposure to sevoflurane after transient ischemia can prevent the development of depressive-like behavior. To test this hypothesis, we induced transient cerebral ischemia via transient occlusion of bilateral common carotid arteries and examined the effects of subsequent repeated exposure to sevoflurane on sucrose preference, locomotor activity, and rearing activity in rats. To explore the putative neurobiological mechanisms, we further investigated the roles of hippocampal CB1 receptor in the behavioral effects of sevoflurane. We found that repeated sevoflurane exposures reversed ischemia-induced depressive-like behaviors. Furthermore, CB1 receptor inhibition in the dorsal hippocampus (DH) abolished the effects of sevoflurane exposures on ischemia-induced depressive-like behaviors. In addition, repeated sevoflurane exposures increased CB1 receptor expression and endocannabinoids levels in the DH of ischemic rats. Moreover, repeated sevoflurane exposures enhanced the expression of ß-arrestin 2, increased the activation of extracellular signal-regulated kinases (ERK)1/2, and promoted the interaction of ß-arrestin 2 and ERK1/2 in the DH, and such effects were reversed by CB1 receptor antagonism in the DH. Finally, ß-arrestin 2 expression and ERK1/2 activation in the DH were critical for the preventative effects of sevoflurane exposures on ischemia-induced depressive-like behaviors. Taken together, our results suggested that sevoflurane exposure after brain ischemia may prevent the development of depression, and such preventative effects of sevoflurane are likely ascribed to the activation of CB1 receptor-mediated ß-arrestin 2-ERK1/2 signaling pathways. We propose that the following mechanisms are critical for the preventative effects of sevoflurane against post-stroke depressive and anxiety behaviors: repeated sevoflurane exposure after transient brain ischemia enhances N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) levels and normalize cannabinoid receptor type 1 (CB1) receptor expression in the dorsal hippocampus, which results in enhanced interaction of ß-arrestin 2 and extracellular signal-regulated kinases (ERK1/2) and increased ERK1/2 activation, leading to decreased depressive and anxiety behaviors. We think these findings should provide a new strategy for treatment of post-stroke depression.

Multiplication method for sparse interferometric fringes.

Fringe analysis in the interferometry has been of long-standing interest to the academic community. However, the process of sparse fringe is always a headache in the measurement, especially when the specimen is very small. Through theoretical derivation and experimental measurements, our work demonstrates a new method for fringe multiplication. Theoretically, arbitrary integral-multiple fringe multiplication can be acquired by using the interferogram phase as the parameter. We simulate digital images accordingly and find that not only the skeleton lines of the multiplied fringe are very convenient to extract, but also the main frequency of which can be easily separated from the DC component. Meanwhile, the experimental results have a good agreement with the theoretic ones in a validation using the classical photoelasticity.

Costunolide Induces Apoptosis through Generation of ROS and Activation of P53 in Human Esophageal Cancer Eca-109 Cells.

Costunolide is a sesquiterpene lactone, which possesses potent anti-cancer properties. However, there is little report about its effects on esophageal cancer. In our study, we investigated the effects of costunolide on the cell viability, cell cycle, and apoptosis in human esophageal cancer Eca-109 cells. It was found that costunolide inhibited the growth of Eca-109 cells in a dose-dependent manner, which was associated with the loss of mitochondrial membrane potential (Δψm ) and the production of ROS. Costunolide induced apoptosis of Eca-109 cells as well as cell cycle arrest in G1/S phase by upregulation of P53 and P21. Costunolide triggered apoptosis in esophageal cancer cells via the upregulation of Bax, downregulation of Bcl-2, and significant activation of caspase-3 and poly ADP-ribose polymerase. These effects were markedly abrogated when cells were pretreated with N-acetylcysteine, a specific reactive oxygen specie inhibitor. These results suggest that costunolide is a potential candidate for the treatment of esophageal cancer.

Cepharanthine induces apoptosis through reactive oxygen species and mitochondrial dysfunction in human non-small-cell lung cancer cells.

Cepharanthine is a medicinal plant-derived natural compound which possesses potent anti-cancer properties. However, there is little report about its effects on lung cancer cells. In this study, we investigated the effects of cepharanthine on the cell viability and apoptosis in human non-small-cell lung cancer H1299 and A549 cells. It was found that cepharanthine inhibited the growth of H1299 and A549 cells in a dose-dependent manner which was associated with the generation of reactive oxygen species(ROS) and the dissipation of mitochondrial membrane potential (Δψm). These effects were markedly abrogated when cells were pretreated with N-acetylcysteine (NAC), a specific ROS inhibitor, indicating that the apoptosis-inducing effect of cepharanthine in lung cancer cells was mediated by ROS. In addition, cepharanthine triggered apoptosis in non-small lung cancer cells via the upregulation of Bax, downregulation of Bcl-2 and significant activation of caspase-3 and PARP. These results provide the rationale for further research and preclinical investigation of cepharanthine's anti-tumor effect against human non-small-cell lung cancer.

Alantolactone Induces Apoptosis and Cell Cycle Arrest on Lung Squamous Cancer SK-MES-1 Cells.

Alantolactone, a sesquiterpene lactone compound, has variety of pharmacological properties, including anti-inflammatory and antineoplastic effects. In our study, alantolactone inhibited cancer cell proliferation. To explore the mechanisms underlying its antitumor action, we further examined apoptotic cells and cell cycle distribution using flow cytometry analysis. Alantolactone triggered apoptosis and induced cell cycle G1/G0 phase arrest. Furthermore, the expressions of caspases-8, -9, -3, PARP, and Bax were significantly upregulated, while antiapoptotic factor Bcl-2 expression was inhibited. In addition, the expressions of cyclin-dependent kinase 4 (CDK4), CDK6, cyclin D3, and cyclin D1 were downregulated by alantolactone. Therefore, our findings indicated that alantolactone has an antiproliferative role on lung squamous cancer cells, and it may be a promising chemotherapeutic agent for squamous lung cancer SK-MES-1 cells.

miRNA expression in breast cancer varies with lymph node metastasis and other clinicopathologic features.

Breast carcinoma is the most common malignant tumor in females, and lymph node (LN) status is one of the most important prognostic factors in patients with breast cancer. MiRNAs have been shown to have important role in oncogenesis, invasion, and metastasis via epigenetic post-transcriptional gene regulation. However, lymphatic metastasis-related miRNAs of breast cancer has not been well documented. The aim of this study was to identify and evaluate miRNAs related to breast cancer LN metastasis and to explore the clinical significance of the differentially expressed miRNAs in patients with breast cancer. The expression of miRNAs in patients with primary breast cancer with LN metastasis and that without LN metastases was compared by miRNA microarray. We further validated the miRNAs (miR-185-5p, miR-339-5p, miR-542-5p, and miR-3923) between LN (n = 31) and nonlymph node (NLN; n = 42) group using real-time reverse transcriptase polymerase chain reaction. Furthermore, the relationship between miRNA expression and clinical pathological features was analyzed. The miRNA microarray initially identified that eight miRNAs (miR-206, miR-3923, miR-181a, miR-92a, miR-421, miR-339-5p, miR-3196, and miR-29b) were downregulated in LN metastasis group, whereas five miRNAs (miR-542-5p, miR-200a, miR-564, miR-451, miR-30c, miR-200b, miR-191-3p, miR-142-5p, and miR-185-5p) were upregulated in LN group when compared with those in NLN group. In the validation cohort, the expression levels of miR-185-5p and miR-542-5p were significantly expressed higher in LN group (P = 0.002 and P = 0.001, respectively), and the expression levels of miR-339-5p and miR-3923 were significantly expressed lower in LN group (P = 0.001 and P = 0.001, respectively). Our results indicate the potential role of miR-185-5p, miR-542-5p, miR-339-5p, and miR-3923 in predicting metastasis to the LN and prognosis in breast cancers.

Spiking neural P systems with a generalized use of rules.

Spiking neural P systems (SN P systems) are a class of distributed parallel computing devices inspired by spiking neurons, where the spiking rules are usually used in a sequential way (an applicable rule is applied one time at a step) or an exhaustive way (an applicable rule is applied as many times as possible at a step). In this letter, we consider a generalized way of using spiking rules by "combining" the sequential way and the exhaustive way: if a rule is used at some step, then at that step, it can be applied any possible number of times, nondeterministically chosen. The computational power of SN P systems with a generalized use of rules is investigated. Specifically, we prove that SN P systems with a generalized use of rules consisting of one neuron can characterize finite sets of numbers. If the systems consist of two neurons, then the computational power of such systems can be greatly improved, but not beyond generating semilinear sets of numbers. SN P systems with a generalized use of rules consisting of three neurons are proved to generate at least a non-semilinear set of numbers. In the case of allowing enough neurons, SN P systems with a generalized use of rules are computationally complete. These results show that the number of neurons is crucial for SN P systems with a generalized use of rules to achieve a desired computational power.

On some classes of sequential spiking neural p systems.

Spiking neural P systems (SN P systems) are a class of distributed parallel computing devices inspired by the way neurons communicate by means of spikes; neurons work in parallel in the sense that each neuron that can fire should fire, but the work in each neuron is sequential in the sense that at most one rule can be applied at each computation step. In this work, with biological inspiration, we consider SN P systems with the restriction that at each step, one of the neurons (i.e., sequential mode) or all neurons (i.e., pseudo-sequential mode) with the maximum (or minimum) number of spikes among the neurons that are active (can spike) will fire. If an active neuron has more than one enabled rule, it nondeterministically chooses one of the enabled rules to be applied, and the chosen rule is applied in an exhaustive manner (a kind of local parallelism): the rule is used as many times as possible. This strategy makes the system sequential or pseudo-sequential from the global view of the whole network and locally parallel at the level of neurons. We obtain four types of SN P systems: maximum/minimum spike number induced sequential/pseudo-sequential SN P systems with exhaustive use of rules. We prove that SN P systems of these four types are all Turing universal as number-generating computation devices. These results illustrate that the restriction of sequentiality may have little effect on the computation power of SN P systems.

Spiking neural P systems with thresholds.

Spiking neural P systems with weights are a new class of distributed and parallel computing models inspired by spiking neurons. In such models, a neuron fires when its potential equals a given value (called a threshold). In this work, spiking neural P systems with thresholds (SNPT systems) are introduced, where a neuron fires not only when its potential equals the threshold but also when its potential is higher than the threshold. Two types of SNPT systems are investigated. In the first one, we consider that the firing of a neuron consumes part of the potential (the amount of potential consumed depends on the rule to be applied). In the second one, once a neuron fires, its potential vanishes (i.e., it is reset to zero). The computation power of the two types of SNPT systems is investigated. We prove that the systems of the former type can compute all Turing computable sets of numbers and the systems of the latter type characterize the family of semilinear sets of numbers. The results show that the firing mechanism of neurons has a crucial influence on the computation power of the SNPT systems, which also answers an open problem formulated in Wang, Hoogeboom, Pan, Paun, and Pérez-Jiménez ( 2010 ).