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The spread of rumors has an important impact on the production and life of human society. Moreover, in the process of rumor propagation, individuals with different educational levels show different degrees of trust and ability to spread rumors. Therefore, a new rumor propagation model was established, which considers the influence of education level on rumor propagation. Initially, the basic reproduction number of the model was calculated. Then, we analyzed the existence and stability of the rumor equilibrium point. Next, based on the principle of Pontryagin's maximum value, we obtained a control strategy, which effectively reduced the spread of rumors. Numerical simulations verified the results of theoretical analysis. The results showed that the higher the education level of the population, the slower the spread of rumors to a certain extent, but it could not prevent the spread of rumors. In addition, through the support of the government and the propaganda of the official media, strengthening education can improve people's education level to a certain extent, and then minimize the speed of rumor propagation.

Abstract Knowledge diffusion in regional innovation ecosystems is an important factor that influences the regional innovation efficiency. In regional innovation ecosystems under digital empowerment, the knowledge diffusion enables the optimal allocation of innovation resources and promotes the sustainable development and ecological evolution of regional innovation ecosystems. In this paper, a SEIR (Susceptible–Exposed–Infected–Recovered) model is proposed for knowledge diffusion in regional innovation ecosystems under digitization. The basic reproduction number of the proposed model is calculated and its stability is validated. Finally, the expressions for the optimal control system and the optimal control parameters are presented. According to the research conclusions of this paper, the knowledge-diffusion ability of innovation agents in an innovation ecosystem affects the knowledge diffusion in a system; the contact rate between innovation agents affects the efficiency of knowledge diffusion in the system and the structure of the system; the digital transmission ability of innovation agents affects the breadth of knowledge diffusion in the system; and the self-learning ability of innovation agents affects the efficiency of knowledge diffusion in the system.The digital technologies help heterogeneous innovation agents in regional innovation ecosystems to break down the knowledge silos. At the same time, the digital technologies enhance the ability of innovation agents to absorb and learn knowledge in regional innovation ecosystems under digitization, thereby increasing the infection rate of knowledge diffusion in such systems.These conclusions extend the theoretical boundaries of innovation ecosystems and knowledge diffusion and offer management implications for enterprises and governments in decision-making.

Currently, most of the wells in X Oilfield are self-flowing wells. In order to adjust the production system of oil wells in time according to the production requirements of oilfields, it is necessary to predict the ceasing–flowing time. Therefore, how to accurately predict the ceasing–flowing time is the main problem faced by the self-flowing well. As the conventional prediction methods only consider the influence of a single variable, the prediction results are not ideal. Combining the production prediction based on the long short-term memory (LSTM) neural network and the inflow and outflow dynamic curves, this study proposes a comprehensive method for predicting the ceasing–flowing time of a flowing well by considering multiple factors. Using the minimum wellhead pressure prediction method, the changes in bottom hole flowing pressure and reservoir pressure are also considered. The practical application results in X Oilfield show that the calculated and predicted results are highly consistent with the actual production data, verifying the reliability of this method. This study can provide a reference for the prediction of oil well ceasing–flowing in other oilfields.

Abstract Cuproptosis is an emerging cell death pathway that depends on the intracellular Cu ions. Elesclomol (ES) as an efficient Cu ionophore can specifically transport Cu into mitochondria and trigger cuproptosis. However, ES can be rapidly removed and metabolized during intravenous administration, leading to a short half‐life and limited tumor accumulation, which hampers its clinical application. Here, the study develops a reactive oxygen species (ROS)‐responsive polymer (PCP) based on cinnamaldehyde (CA) and polyethylene glycol (PEG) to encapsulate ES‐Cu compound (EC), forming ECPCP. ECPCP significantly prolongs the systemic circulation of EC and enhances its tumor accumulation. After cellular internalization, the PCP coating stimulatingly dissociates exposing to the high‐level ROS, and releases ES and Cu, thereby triggering cell death via cuproptosis. Meanwhile, Cu2+‐stimulated Fenton‐like reaction together with CA‐stimulated ROS production simultaneously breaks the redox homeostasis, which compensates for the insufficient oxidative stress treated with ES alone, in turn inducing immunogenic cell death of tumor cells, achieving simultaneous cuproptosis and immunotherapy. Furthermore, the excessive ROS accelerates the stimuli‐dissociation of ECPCP, forming a positive feedback therapy loop against tumor self‐alleviation. Therefore, ECPCP as a nanoplatform for cuproptosis and immunotherapy improves the dual antitumor mechanism of ES and provides a potential optimization for ES clinical application.

Neuroscientists have recognized the importance of astrocytes in regulating neurological function and their influence on the release of glial transmitters. Few studies, however, have focused on the effects of general anesthetic agents on neuroglia or astrocytes. Astrocytes can also be an important target of general anesthetic agents as they exert not only sedative, analgesic, and amnesic effects but also mediate general anesthetic-induced neurotoxicity and postoperative cognitive dysfunction. Here, we analyzed recent advances in understanding the mechanism of general anesthetic agents on astrocytes, and found that exposure to general anesthetic agents will destroy the morphology and proliferation of astrocytes, in addition to acting on the receptors on their surface, which not only affect Ca2+ signaling, inhibit the release of brain-derived neurotrophic factor and lactate from astrocytes, but are even involved in the regulation of the pro- and anti-inflammatory processes of astrocytes. These would obviously affect the communication between astrocytes as well as between astrocytes and neighboring neurons, other neuroglia, and vascular cells. In this review, we summarize how general anesthetic agents act on neurons via astrocytes, and explore potential mechanisms of action of general anesthetic agents on the nervous system. We hope that this review will provide a new direction for mitigating the neurotoxicity of general anesthetic agents.

Abstract Investor sentiment contagion has a profound influence on economic and social development. This paper explores the diverse influences of various investor sentiments in modern society on the economy and society. It also investigates the interference of various uncertain factors on investor sentiments in the modern economy and society. On this basis, the dual-system stochastic SPA2G2R model was constructed, incorporating positive and negative sentiments, as well as a supervision and isolation mechanism. The global existence of positive solutions was established, and sufficient conditions for the disappearance and steady distribution of investor sentiment were calculated. An optimal control strategy for the stochastic model was put forward, with numerical simulation supporting the theoretical analysis results. A comparison with parameter changes in the deterministic model was also conducted. The research reveals a competitive relationship between different investor sentiments. Enhancing societal guidance mechanisms promotes positive investor sentiment contagion. Timely control by the supervisory department effectively curbs the spread of investor sentiment. Additionally, white noise promotes investor sentiment contagion, suggesting effective regulation through control of noise intensity and disturbance parameters.

Abstract Background Prolonged length of stay in post-anesthesia care unit (PLOS in PACU) is a combination of risk factors and complications that can compromise quality of care and operating room efficiency. Our study aimed to develop a nomogram to predict PLOS in PACU of patients undergoing elective surgery. Methods Data from 24017 patients were collected. Least absolute shrinkage and selection operator (LASSO) was used to screen variables. A logistic regression model was built on variables determined by a combined method of forward selection and backward elimination. Nomogram was designed with the model. The nomogram performance was evaluated with the area under the receiver operating characteristic curve (AUC) for discrimination, calibration plot for consistency between predictions and actuality, and decision curve analysis (DCA) for clinical application value. Results A nomogram was established based on the selected ten variables, including age, BMI < 21 kg/m2, American society of Anesthesiologists Physical Status (ASA), surgery type, chill, delirium, pain, naloxone, operation duration and blood transfusion. The C-index value was 0.773 [95% confidence interval (CI) = 0.765 - 0.781] in the development set and 0.757 (95% CI = 0.744-0.770) in the validation set. The AUC was > 0.75 for the prediction of PLOS in PACU. The calibration curves revealed high consistencies between the predicted and actual probability. The DCA showed that if the threshold probability is over 10% , using the models to predict PLOS in PACU and implement intervention adds more benefit. Conclusions This study presented a nomogram to facilitate individualized prediction of PLOS in PACU for patients undergoing elective surgery.

Variations in the tumor genome can result in allelic changes compared to the reference profile of its homogenous body source on genetic markers. This brings a challenge to source identification of tumor samples, such as clinically collected pathological paraffin-embedded tissue and sections. In this study, a probabilistic model was developed for calculating likelihood ratio (LR) to tackle this issue, which utilizes short tandem repeat (STR) genotyping data. The core of the model is to consider tumor tissue as a mixture of normal and tumor cells and introduce the incidence of STR variants (φ) and the percentage of normal cells (Mxn) as a priori parameters when performing calculations. The relationship between LR values and φ or Mxn was also investigated. Analysis of tumor samples and reference blood samples from 17 colorectal cancer patients showed that all samples had Log10(LR) values greater than 1014. In the non-contributor test, 99.9% of the quartiles had Log10(LR) values less than 0. When the defense’s hypothesis took into account the possibility that the tumor samples came from the patient’s relatives, LR greater than 0 was still obtained. Furthermore, this study revealed that LR values increased with decreasing φ and increasing Mxn. Finally, LR interval value was provided for each tumor sample by considering the confidence interval of Mxn. The probabilistic model proposed in this paper could deal with the possibility of tumor allele variability and offers an evaluation of the strength of evidence for determining tumor origin in clinical practice and forensic identification.

High sensitivity and selectivity and short response and recovery times are important for practical conductive polymer gas sensors. However, poor stability, poor selectivity, and long response times significantly limit the applicability of single-phase conducting polymers, such as polypyrrole (PPy). In this study, PPy/MoS2 composite films were prepared via chemical polymerization and mechanical blending, and flexible thin-film resistive NO2 sensors consisting of copper heating, fluorene polyester insulating, and PPy/MoS2 sensing layers with a silver fork finger electrode were fabricated on a flexible polyimide substrate using a flexible electronic printer. The PPy/MoS2 composite films were characterized using X-ray diffraction, Fourier-transform infrared spectroscopy, and field-emission scanning electron microscopy. A home-built gas sensing test platform was built to determine the resistance changes in the composite thin-film sensor with temperature and gas concentration. The PPy/MoS2 sensor exhibited better sensitivity, selectivity, and stability than a pure PPy sensor. Its response to 50 ppm NO2 was 38% at 150 °C, i.e., 26% higher than that of the pure PPy sensor, and its selectivity and stability were also higher. The greater sensitivity was attributed to p–n heterojunction formation after MoS2 doping and more gas adsorption sites. Thus, PPy/MoS2 composite film sensors have good application prospects.

Information dissemination has a significant impact on social development. This paper considers that there are many stochastic factors in the social system, which will result in the phenomena of information cross-dissemination and variation. The dual-system stochastic susceptible-infectious-mutant-recovered model of information cross-dissemination and variation is derived from this problem. Afterward, the existence of the global positive solution is demonstrated, sufficient conditions for the disappearance of information and its stationary distribution are calculated, and the optimal control strategy for the stochastic model is proposed. The numerical simulation supports the results of the theoretical analysis and is compared to the parameter variation of the deterministic model. The results demonstrate that cross-dissemination of information can result in information variation and diffusion. Meanwhile, white noise has a positive effect on information dissemination, which can be improved by adjusting the perturbation parameters.

Introduction Focal segmental glomerulosclerosis (FSGS) is a common glomerulopathy with unclear mechanism. The demand for FSGS clinical diagnostic biomarkers has not yet been met. Circular RNA (circRNA) is a novel non-coding RNA with multiple functions, but its diagnostic value for FSGS remains unexplored. This study aimed to identify circRNAs that could aid in early clinical diagnosis and to investigate their mechanisms in podocyte injury. Methods The signature of plasma circRNAs for FSGS was identified by circRNA microarray. The existence of circRNAs was confirmed by qRT-PCR, RNase R assay, and DNA sequencing. Plasma levels of circRNAs were evaluated by qRT-PCR. The diagnostic value was appraised by receiver operating characteristic curve. The circRNA-miRNA-mRNA network was built with Cytoscape 7.3.2. Statistically significant differences were calculated by the Mann-Whitney U-test. Results A total of 493 circRNAs (165 upregulated, 328 downregulated) were differentially expressed in the plasma of FSGS patients (n = 3) and normal controls (n = 3). Eight candidate circRNAs were demonstrated to be circular and stable transcripts. Among them, hsa_circ_0001230 and hsa_circ_0023879 were significantly upregulated in FSGS patients (n = 29) compared to normal controls (n = 51). The areas under the curve value of hsa_circ_0001230 and hsa_circ_0023879 were 0.668 and 0.753, respectively, while that of two-circRNAs panel was 0.763. The RNA pull-down analysis revealed that hsa_circ_0001230 and hsa_circ_0023879 could sponge hsa-miR-106a. Additionally, hsa_circ_0001230 and hsa_circ_0023879 positively regulated hsa-miR-106a target genes phosphatase and tensin homolog (PTEN) and Bcl-2-like protein 11 (BCL2L11) in podocytes. Conclusion Hsa_circ_0001230 and hsa_circ_0023879 are novel blood biomarkers for FSGS. They may regulate podocyte apoptosis by competitively binding to hsa-miR-106a.

Prostate specific antigen (PSA), as a biomarker, plays important roles in early diagnosis of male prostate diseases, especially prostate cancer. In this study, a novel electrochemical probe polymer of poly(ferriporphyrin-co-acrylamide) was synthesized, by further combined with reduced graphene oxide and gold nanoparticles, and oriented immobilization of PSA antibody, a label-free electrochemical immunosensor was obtained, and then successfully applied in the determination of PSA in 10 % non-antigen serum system. The prepared biosensor expressed high selectivity toward PSA, with a LOD of 0.001 ng mL−1, a linear range of 0.01–110 ng mL−1, and a sensitivity of 15.78 µA mL ng−1. What’s more, it showed good stability, well repeatability and high selectivity in the real PSA sample detection. This work provided certain references for the design of the new electrochemical probes and the detection of tumor markers.

Abstract The 2022 heatwave in China featured record‐shattering high temperatures, raising questions about its origin and possible link to global warming. Here we show that the maximum temperature anomalies over Central China reached 13.1°C in the summer of 2022, which is ∼4.2σ above the 1981–2010 mean with a return period of tens of thousands of years. Our results suggested that the persistent high‐pressure anomaly and associated extreme heatwave likely resulted mainly from internal variability, although anthropogenic warming has increased the probability of such extreme heatwaves. We also estimate that the 2022‐like heatwave becomes six to seven times more likely under persistent high‐pressure conditions when compared to stochastic circulation states. Due to a shift toward warmer mean temperatures and a flattening of the probability distribution function, such rare extreme heatwaves are projected to become much more common at a global warming level of 4°C, occurring once about every 8.5 years.

Abstract FMR1, a new m6A reader, is known to be involved in the regulation of cancer progression. However, its role, regulatory mechanism, and clinical significance in colorectal cancer (CRC) are elusive. Here, we showed that FMR1 was upregulated in CRC, and it promoted proliferation and metastasis of CRC cells in vitro and in vivo. Mechanically, FMR1 recognized the m6A-modification site in EGFR mRNA, a key molecule in cancer occurrence and targeted therapy, sustained its stability and maintained its expression in an m6A-dependent manner, thereby promoting the tumorigenesis and metastasis of CRC. And the effect of FMR1 knockdown in CRC cells could be abolished by METTL3. Furthermore, FMR1 shRNA plasmid carried by attenuated Salmonella has an effective anti-tumor effect in vivo. Collectively, we identified the METTL3/FMR1/EGFR axis in the progression of CRC. This novel mechanism indicated that the METTL3/FMR1/EGFR axis is a potential target for early therapeutic intervention in CRC progression.

Colorectal cancer (CRC) is a lethal malignancy worldwide. Exosomes are extracellular vesicles derived from the endosomal pathway of nearly all cells and can be found in body fluids. They can be considered an intercellular system in the human body that can mediate near- and long-distance intercellular communication due to their features and functions. Investigations have revealed that exosomes are participated in different processes, physiologically and pathologically, especially in cancer. However, the clinical value of exosomes and their mechanisms of action in CRC are unclear and have not been systematically assessed. The purpose of this review is to discuss how exosomes play a role in the occurrence and development of CRC, with a particular focus on the functions and underlying mechanisms of tumor-derived exosomes as well as non-tumor-derived exosomes. We also describe the evidence that exosomes can be used as diagnostic and prognostic markers for CRC. In addition, the possibilities of exosomes in CRC clinical transformation are also discussed.

Environmental factors in social systems affect information spreading at all times. This paper proposes a stochastic S2EIR model that considers the presence of super-spreaders and implicit exposers in information spreading, as well as the stochastic perturbation of model parameters. The existence of a global positive solution using the Itô′s formula is then demonstrated. Sufficient conditions for information disappearance and smooth distribution of information are calculated by using the Borel–Cantelli lemma and the strong law of large numbers. Furthermore, the optimal control strategy for the stochastic model is proposed using the Hamiltonian function. The results of the theoretical analysis are supported by numerical simulations and compared to the parameter variations of the deterministic model. The results of this study indicate that white noise facilitates the spread of information. The intensity of perturbation is proportional to the fluctuation of information spreading. Controlling random parameters can effectively facilitate the spread of information. For positive information, the randomness and complexity of the social system should be utilized to increase the spread of information. In contrast, for negative information, randomness in the social system should be suppressed to the greatest extent possible to limit information dissemination.

Abstract Cross-transmission of information has a profound influence on the progress of science and technology and the discipline integration in the field of education. In this work, knowledge gained from the viral recombination and variation in COVID-19 transmission is applied to information transmission. Virus recombination and virus variation are similar to the crossing and information fusion phenomena in information transmission. An S2I4MR model with information crossing and variation is constructed. Then, the local and global asymptotic stabilities of the information-free equilibrium and information-existence equilibrium are analyzed. Additionally, the basic reproduction number $$R_0$$ R 0 of the model is calculated. As such, an optimal control strategy is hereby proposed to promote the cross-transmission of information and generate variant information. The numerical simulations support the results of the theoretical analysis and the sensitivity of the system towards certain control parameters. In particular, the results show that strengthening information crossing promotes the generation of variant information. Furthermore, encouraging information exchange and enhancing education improve the generation of information crossing and information variation.

Leaf and tuber extracts of Curcuma wenyujin contain a mixture of curcuminoids. However, the curcuminoid constituents and their molecular mechanisms are poorly understood, and the relevant curcumin synthases remain unclear. In this study, we comprehensively compared the metabolite profiles of the leaf and tuber tissues of C. wenyujin. A total of 11 curcuminoid metabolites were identified and exhibited differentially changed contents in the leaf and tuber tissues. An integrated analysis of metabolomic and transcriptomic data revealed the proposed biosynthesis pathway of curcuminoid. Two candidate type Ⅲ polyketide synthases (PKSs) were identified in the metabolically engineering yeasts, indicating that CwPKS1 and CwPKS2 maintained substrate and product specificities. Especially, CwPKS1 is the first type Ⅲ PKS identified to synthesize hydrogenated derivatives of curcuminoid, dihydrocurcumin and tetrehydrocurcumin. Interestingly, the substitution of the glycine at position 219 with aspartic acid (G219D mutant) resulted in the complete inactivation of CwPKS1. Our results provide the first comparative metabolome analysis of C. wenyujin and functionally identified type Ⅲ PKSs, giving valuable information for curcuminoids biosynthesis.

Boosting transcorneal permeability and pharmacological activity of drug poses a great challenge in the field of ocular drug delivery. In the present study, we propose a drug-peptide supramolecular hydrogel based on anti-inflammatory drug, dexamethasone (Dex), and Arg-Gly-Asp (RGD) motif for boosting transcorneal permeability and pharmacological activity via the ligand-receptor interaction. The drug-peptide (Dex-SA-RGD/RGE) supramolecular hydrogel comprised of uniform nanotube architecture formed spontaneously in phosphate buffered saline (PBS, pH = 7.4) without external stimuli. Upon storage at 4 °C, 25 °C, and 37 °C for 70 days, Dex-SA-RGD in hydrogel did not undergo significant hydrolysis, suggesting great long-term stability. In comparison to Dex-SA-RGE, Dex-SA-RGD exhibited a more potent in vitro anti-inflammatory efficacy in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages via the inhibition of nuclear factor кB (NF-κB) signal pathway. More importantly, using drug-peptide supramolecular hydrogel labeled with 7-nitro-2,1,3-benzoxadiazole (NBD), the Dex-SA-K(NBD)RGD showed increased performance in terms of integrin targeting and cellular uptake compared to Dex-SA-K(NBD)RGE, as revealed by cellular uptake assay. On topical instillation in rabbit's eye, the proposed Dex-SA-K(NBD)RGD could effectively enhance the transcorneal distribution and permeability with respect to the Dex-SA-K(NBD)RGE. Overall, our findings demonstrate the performance of the ligand-receptor interaction for boosting transcorneal permeability and pharmacological activity of drug.

Abstract Humanoid robots, intelligent machines resembling the human body in shape and functions, cannot only replace humans to complete services and dangerous tasks but also deepen the own understanding of the human body in the mimicking process. Nowadays, attaching a large number of sensors to obtain more sensory information and efficient computation is the development trend for humanoid robots. Nevertheless, due to the constraints of von Neumann‐based structures, humanoid robots are facing multiple challenges, including tremendous energy consumption, latency bottlenecks, and the lack of bionic properties. Memristors, featured with high similarity to the biological elements, play an important role in mimicking the biological nervous system. The memristor‐based nervous system allows humanoid robots to obtain high energy efficiency and bionic sensing properties, which are similar properties to the biological nervous system. Herein, this article first reviews the biological nervous system and memristor‐based nervous system thoroughly, including the structures and also the functions. The applications of memristor‐based nervous systems are introduced, the difficulties that need to be overcome are put forward, and future development prospects are also discussed. This review can hopefully provide an evolutionary perspective on humanoid robots and memristor‐based nervous systems.

Abstract The Tol–Pal system of Gram-negative bacteria is necessary for maintaining outer membrane integrity. It is a multiprotein complex of five envelope proteins, TolQ, TolR, TolA, TolB, and Pal. These proteins were first investigated in E. coli, and subsequently been identified in many other bacterial genera. However, the function of the Tol–Pal system in Salmonella Choleraesuis pathogenesis is still unclear. Here, we reported the role of three of these proteins in the phenotype and biology of S. Choleraesuis. We found that mutations in tolA, tolB, and tolR caused severe damage to the cell wall, which was supported by observing the microstructure of spherical forms, long chains, flagella defects, and membrane blebbing. We confirmed that all the mutants significantly decreased S. Choleraesuis survival when exposed to sodium deoxycholate and exhibited a high sensitivity to vancomycin, which may be explained by the disruption of envelope integrity. In addition, tolA, tolB, and tolR mutants displayed attenuated virulence in a mouse infection model. This could be interpreted as a series of defective phenotypes in the mutants, such as severe defects in envelope integrity, growth, and motility. Further investigation showed that all the genes participate in outer membrane vesicles (OMVs) biogenesis. Interestingly, immunization with OMVs from ΔtolB efficiently enhanced murine viability in contrast to OMVs from the wild-type S. Choleraesuis, suggesting its potential use in vaccination strategies. Collectively, this study provides an insight into the biological role of the S. Choleraesuis Tol–Pal system.

Carbon fiber–reinforced polymers (CFRPs) have excellent tensile strength and great resistance to chloride ion corrosion. In the 21st century of rapid development in marine construction, the composite structure of CFRP and coral aggregate concrete (CAC) has broad development prospects and great research value. This paper proposes a CFRP–confined coral aggregate concrete (CCAC) column as a novel composite column suitable for use in marine environments. Eighteen CCAC circular stub columns were constructed, and compression tests were carried out under axial and eccentric loads. The compression behavior, including the load–carrying capacity, stress–strain relationship, and ductility of CCAC stub columns was investigated. Test results show that the CFRP sheets greatly improve the load–carrying capacity and ductility of the CAC stub columns. Among the three influencing factors, the influence on the load–carrying capacity and ductility of the CCAC stub columns is eccentric distance, the number of CFRP layers, and the CAC strength in descending order. Finally, the load–carrying capacity calculation method and the stress–strain relationship of CCAC stub columns under axial compression were established, and an eccentric reduction coefficient was proposed to calculate the load–carrying capacity of CCAC columns under different eccentric distances.

BackgroundSevoflurane exposure at brain developmental stages has been reported to induce neurotoxicity and, subsequently, results in learning deficits at the juvenile age. In this study, we aimed to investigate the effects of prior early-age sevoflurane exposure on locomotor activity, anxiety, CA1-dependent learning, and spatial memory, as well as synapse changes in mice.MethodsTotally, 3% sevoflurane was given to neonatal mice at postnatal day 7 for 4 h. These sevoflurane-treated mice were later subjected to open field and Morris water maze tests at their adult age (postnatal days 60–90) to assess their motor activity and spatial learning ability, respectively. The brain slices of sevoflurane-treated and control mice were examined for dendritic spine density and long-term potentiation (LTP) features following behavior tests (postnatal day 60). Protein levels of N-methyl-D-aspartate (NMDA) receptor subtypes and PSD95 in brain lysate were measured by using immunoblotting at the same age (postnatal day 60).ResultsPrior early-age sevoflurane exposure increased the overall moving distance, prolonged the central-area lingering time, and increased the central-area entries of adult mice. Sevoflurane-treated mice spent more time in the target quadrant during the probe test. An increase of the spine density of pyramidal neurons in the CA1 region was observed in sevoflurane-treated mice. NMDA receptor GluN2A subunit, but not the GluN2B or PSD95, was increased in the brain lysate of sevoflurane-treated mice compared with that of control mice. LTP in the hippocampus did not significantly differ between sevoflurane-treated and control mice.ConclusionExposure to sevoflurane for mice during an early brain developmental stage (P7) induces later-on hyperactivity, anxiety-free, and enhancement of memory retention. These observations shed light on future investigations on the underlying mechanisms of sevoflurane’s effect on neuronal development.

Tumor-infiltrating immune cells are associated with prognosis and immunotherapy targets in colorectal cancer (CRC). The recently developed CIBERSORT method allows immune cell analysis by deconvolution of high-throughput data onto gene expression. In this study, we analyzed the relative proportions of immune cells in GEO (94 samples) and TCGA (522 samples) CRC data based on the CIBERSORT method. A total of 22 types of tumor-infiltrating immune cells were evaluated. Combined with GEO and TCGA data, it was found that naive B cells, M2 macrophages, and resting mast cells were highly expressed in normal tissues, while M0 macrophages, M1 macrophages, activated mast cells, and neutrophils were highly expressed in tumors. Moreover, we constructed a prognostic model by infiltrating immune cells that showed high specificity and sensitivity in both the training (AUC of 5-year survival = 0.699) and validation (AUC of 5-year survival = 0.844) sets. This provides another basis for clinical prognosis. The results of multiple immunofluorescence detection showed that there were differences in the results of bioinformatics analysis. Neutrophils were highly expressed in normal tissues, and M2 macrophages were highly expressed in tumor tissues. Collectively, our data suggested that infiltrating immune cells in CRC may be an important determinant of prognosis and immunotherapy.

Federated Learning (FL) is a newly emerged federated optimization technique for distributed data in a federated network. The participants in FL that train the model locally are classified into client nodes. The server node assumes the responsibility to aggregate local models from client nodes without data moving. In this regard, FL is an ideal solution to protect data privacy at each node of the network. However, the raw data generated on each node are unlabeled, making it impossible for FL to apply these data directly to train a model. The large volume of data annotating work prevents FL from being widely applied in the real world, especially for online scenarios, where the data are generated continuously. Meanwhile, the data generated on different nodes tend to be differently distributed. It has been proved theoretically and experimentally that non-independent and identically distributed (non-IID) data harm the performance of FL. In this article, we design a semi-federated active learning (semi-FAL) framework to tackle the annotation and non-IID problems jointly. More specifically, the server node can provide (i) a pre-trained model to help each client node annotate the local data uniformly and (ii) an estimation of the global gradient to help correct the local gradient. The evaluation results demonstrate our semi-FAL framework can efficiently handle unlabeled online network data and achieves high accuracy and fast convergence.

Colorectal cancer (CRC) is the most common malignancy of the gastrointestinal, however, the underlying mechanisms of CRC remain largely unknown. New evidence suggests that the PI3K/AKT/mTOR pathway is closely related to CRC. PI3K/AKT/mTOR is a classical signaling pathway that is involved in a variety of biological processes, such as regulating cellular metabolism, autophagy, cell cycle progression, cell proliferation, apoptosis, and metastasis. Therefore, it plays a crucial role in the occurrence and development of CRC. In this review, we focus on the role of the PI3K/AKT/mTOR pathway in CRC, and its application of to the treatment of CRC. We review the importance of the PI3K/AKT/mTOR signaling pathway in tumorigenesis, proliferation and progression, and pre-clinical and clinical experience with several PI3K/AKT/mTOR pathway inhibitors in CRC.

Nodal shape functions and their gradients are vital in transferring physical information within the material point method (MPM). Their continuity is related to numerical stability and accuracy, and their support domain size affects computational efficiency. In this paper, a scheme of aggregated and smoothed Bernstein functions is proposed to improve the MPM. In detail, the Bernstein polynomials are smoothed with a convolution reformation to eliminate the cell crossing error, and an aggregation strategy is implemented to cut down the node amount required for field probing. Hierarchical MPM variants are obtained with choices of original Bernstein polynomials and degrees of smoothing. Numerical examples show that mass, momentum, and energy conservations are all well met, and no cell crossing noise exists. In addition, solution accuracy and numerical stability are significantly improved in large deformation problems.

Optical fiber sensing is a novel sensing technology with the advantages of anti-electromagnetic interference, anti-corrosion and high sensitivity suiting for many special applications. In this paper, a Michelson optical fiber voice monitoring system is introduced and a novel sound extraction algorithm is proposed to improve the noise stability of it. The voice demodulated by a traditional algorithm based on $3\times 3$ fiber coupler has unstable background noise intensity with the change of the working point of the interferometer. The unstable noise comes from the shot noise of photodetectors. The sound extraction method proposed in this paper uses the relation between shot noise and light intensity to smooth the unstable noise and does not affect the quality of voice monitoring. Voice monitoring systems using this algorithm have stable monitoring quality without any working point control technology. The fluctuation range of noise intensity in 300~3500 Hz decrease from 10 dB to less than 2 dB compared with the traditional demodulation algorithm. Such a method and system can be widely used in many special voice monitoring application fields such as prison, underground utility tunnel.

Abstract Background Septic-acute respiratory distress syndrome (ARDS), characterized by the acute lung injury (ALI) secondary to aberrant systemic inflammatory response, has high morbidity and mortality. Despite increased understanding of ALI pathogenesis, the therapies to prevent lung dysfunction underlying systemic inflammatory disorder remain elusive. The high density lipoprotein (HDL) has critical protective effects in sepsis and its dysfunction has a manifested contribution to septic organ failure. However, the adverse changes in HDL composition and function in septic-ARDS patients are large unknown. Methods To investigate HDL remodeling in septic-ARDS, we analyzed the changes of HDL composition from 40 patients with septic-ARDS (A-HDL) and 40 matched normal controls (N-HDL). To determine the deleterious functional remodeling of HDL, A-HDL or N-HDL was administrated to C57BL/6 and apoA-I knock-out (KO) mice after cecal ligation and puncture (CLP) procedure. Mouse lung microvascular endothelial cells (MLECs) were further treated by these HDLs to investigate whether the adverse effects of A-HDL were associated with endothelial dysfunction. Results Septic-ARDS patients showed significant changes of HDL composition, accompanied with significantly decreased HDL-C. We further indicated that A-HDL treatment aggravated CLP induced ALI. Intriguingly, these deleterious effects of A-HDL were associated with pulmonary endothelial dysfunction, rather than the increased plasma lipopolysaccharide (LPS). Further in vitro results demonstrated the direct effects of A-HDL on MLECs, including increased endothelial permeability, enhanced expressions of adhesion proteins and pro-inflammatory cytokines via activating NF-κB signaling and decreased junction protein expression. Conclusions Our results depicted the remodeling of HDL composition in sepsis, which predisposes lung to ARDS via inducing ECs dysfunction. These results also demonstrated the importance of circulating HDL in regulating alveolar homeostasis.

Information transmission significantly impacts social stability and technological advancement. This paper compares the phenomenon of "Super transmission" and "Asymptomatic infection" in COVID-19 transmission to information transmission. The former is similar to authoritative information transmission individuals, whereas the latter is similar to individuals with low acceptance in information transmission. It then constructs an S2EIR model with transmitter authority and individual acceptance levels. Then, it analyzes the asymptotic stability of information-free and information-existence equilibrium on a local and global scale, as well as the model's basic reproduction number, R0. Distinguished with traditional studies, the population density function and Hamiltonian function are constructed by taking proportion of "Super transmitter" and proportion of hesitant group turning into transmitters as optimization control variables. Based on the Pontryagin maximum principle, an optimal control strategy is designed to effectively facilitate information transmission. The numerical simulation corroborates the theoretical analysis results and the system's sensitivity to control parameter changes. The research results indicate that the authoritative "Super transmitter" has a beneficial effect on information transmission. In contrast, the "Asymptomatic infected individual" with poor individual acceptance level negatively affects information transmission.

Media reports and the number of rumors in the media have an important impact on the spread of rumors. Currently, studies that consider these two factors comprehensively on rumor propagation are uncommon. It is better to consider both effects comprehensively than to consider one of them alone. In this paper, we established a new propagation model, which regards the number of rumors in the media as a subclass that changes with time, and then comprehensively considered the effect of these two factors on the process of rumor propagation. We proved the existence and stability of equilibrium points of the model. Then, we selected two reasonable control variables: science popularization intensity and punishment intensity. We find that the control effects are optimal when these two control variables take the maximum value. Theoretical analysis and numerical simulation results showed that positive media publicity can reduce the spread of rumors, but cannot stop the spread of rumors. And under the parameters given in this paper, the optimal control parameter values satisfying the constraints can be calculated through quantitative analysis. This method provided a new idea for studying the optimal control of rumor propagation.

To evaluate the effects of gelatin and starch encapsulated vitamin A on growth performance, immune status and antioxidant capacity in weaned piglets, a total of 96 weaned piglets (body weight = 9.11 ± 0.03 kg, 30-d-old) were randomly allotted to 3 treatments with 4 replications of 8 piglets each. The 3 treatments were control diet (basal diet without addition of vitamin A), gelatin vitamin A diet (basal diet + 13,500 IU/kg gelatin encapsulated vitamin A), and starch vitamin A diet (basal diet + 13,500 IU/kg starch encapsulated vitamin A), respectively. The results showed that piglets fed starch vitamin A diet had significantly higher final body weight and average daily gain compared to those in control and gelatin vitamin A groups (P

The novel pleuromutilin derivative, which showed excellent in vitro antibacterial activity against MRSA, 22-(2-(2-(4-((4-(4-nitrophenyl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)acetamido)phenyl)thioacety-l-yl-22-deoxypleuromutilin (Z33), was synthesized and characterized in our previous work. In this study, the preliminary pharmacodynamics and safety of Z33 were further evaluated. In in vitro antibacterial activity assays, Z33 was found to be a potent bactericidal antibiotic against MRSA that induced dose-dependent growth inhibition and long-term post-antibiotic effect (PAE). The drug-resistance test demonstrated that Z33 possessed a narrow mutant selection window and lower propensities to select resistance than that of tiamulin. Cytochrome P450 (CYP450) inhibition assay determined that the inhibitory effect of Z33 was similar to that of tiamulin against the activity of CYP3A4, and was lower than that of tiamulin on the activity of CYP2E1. Toxicity determination showed that both Z33 and tiamulin displayed low cytotoxicity of RAW264.7 cells. Furthermore, Z33 was found to be a high-security compound with a 50% lethal dose (LD50) above 5000 mg/kg in the acute oral toxicity test in mice. In an in vivo antibacterial activity test, Z33 displayed better therapeutic effectiveness than tiamulin in the neutropenic mouse thigh infection model. In summary, Z33 was worthy of further development as a highly effective and safe antibiotic agent against MRSA infection.

Purpose: This study evaluated the efficacy of retrobulbar ropivacaine plus dexmedetomidine compared with systemic fentanyl in pediatric vitreoretinal (VR) surgery. Methods: This prospective double-blind, randomized controlled study was performed in 60 children undergoing VR surgery, age from 2 to 7 years. After general anesthesia, the following procedure was administrated: (1) retrobulbar block with 0.5% ropivacaine plus dexmedetomidine 1 μg/kg (group RD, n = 20), (2) retrobulbar block with 0.5% ropivacaine (group RB, n = 20), and (3) control group with general anesthesia only (group F, n = 20). Hemodynamics, postoperative pain scores, anesthetics consumption (remifentanil, propofol, fentanyl), and emergence agitation were recorded. Results: Respiratory depression was observed in 7 of the 20 patients in group F after the laryngeal mask airway was removed in the operating room, compared with none in groups RD and RB. All patients in group F required intraoperative rescue fentanyl (average intraoperative fentanyl consumption, 26.6 ± 12.6 μg per patient). Some rescue fentanyl was required in group RB (three patients required one dose of rescue fentanyl). Patients in group RD required none. Groups RD and RB reported lower pain scores than group F at 4 h postoperatively (RD group: P < 0.001; RB group: P =0.002); pain scores in group RD were lower than that in group F at 6 h postoperatively (P < 0.001). Conclusion: Retrobulbar dexmedetomidine as an adjuvant to ropivacaine is a safe and effective alternative to systemic fentanyl. This regimen provides better pain management, hemodynamic stability, and stress response suppression in pediatric VR surgery.

Positioning the pixels of ground control points (GCPs) in drone images is an issue of great concern in the field of drone photogrammetry. The current mainstream automatic approaches are based on standardized markers, such as circular coded targets and point coded targets. There is no denying that introducing standardized markers improves the efficiency of positioning GCP pixels. However, the low flexibility leads to some drawbacks, such as the heavy logistical input in placing and maintaining GCP markers. Especially as drone photogrammetry steps into the era of large scenes, the logistical input in maintaining GCP markers becomes much more costly. This paper proposes a novel positioning method applicable for non-standardized GCPs. Firstly, regions of interest (ROIs) are extracted from drone images with stereovision technologies. Secondly, the quality of ROIs is evaluated using image entropy, and then the outliers are filtered by an adjusted boxplot. Thirdly, pixels of interest are searched with a corner detector, and the precise imagery coordinates are obtained by subpixel optimization. Finally, the verification was carried out in an urban scene, and the results show that this method has good applicability to the GCPs on road traffic signs, and the accuracy rate is over 95%.

Abstract The research about nanofluids has been explosively increasing due to their fascinating properties in heat or mass transportation, fluidity, and dispersion stability for energy system applications (e.g., solar collectors, refrigeration, heat pipes, and energy storage). This second part of the review summarizes recent research on application of TiO2 nanofluids and identifies the challenges and opportunities for the further exploration of TiO2 nanofluids. It is expected that the two exhaustive reviews could be a helpful reference guide for researchers to update the knowledge on research status of TiO2 nanofluids, and the critical comments, challenges, and recommendations could be useful for future study directions.

Abstract As a new generation of working fluid, nanofluid has long been regarded as a hot research topic in the past three decades. Many review papers have provided comprehensive and systematic summaries on the development and state-of-the-art of nanofluids. As of today, it is becoming increasingly difficult to provide a comprehensive review of all kinds of nanofluids owing to the huge amounts of the related literatures. And many controversies and inconsistencies in the reported arguments have been observed in various nanofluids. Meanwhile, the systematic or comprehensive reviews on a certain kind of nanofluid are insufficient. Therefore, this review focuses on the research about one of the hottest kinds viz. TiO2 nanofluid, which has captured scientists’ great attention because of its interesting and comprehensive properties such as sensational dispersivity, chemical stability, and non-toxicity. Due to the preparation of nanofluids is the prerequisite and physical properties are critical factors for further applications, this first part of the review summarizes recent research on preparation, stability, and physical properties of TiO2 nanofluids.

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths and a major health problem. High mobility group box 3 (HMGB3), a member of the high-mobility group box (HMGB) family, was reported to be over-expressed in gastric carcinoma and bladder cancer. However, the function of HMGB3 in CRC remains unclear. Here, we found that HMGB3 was up-regulated in CRC at both mRNA and protein levels. qRT-PCR results showed that high expression of HMGB3 had positive correlation with serosal invasion, lymph metastasis, and tumor-node-metastasis (TNM) stage in CRC patient. Functional experiments showed that HMGB3 can promote CRC cells proliferation and migration in vitro. Moreover, we found HMGB3 can active WNT/β-catenin pathway to increase the expression level of c-Myc and MMP7. These results may be the reason for HMGB3 oncogene role in CRC. In summary, our data indicated that HMGB3 may serve as an oncoprotein and could be used as a potential prognostic marker in CRC.

The effects of general anesthetic agents (GAAs) on microglia and their potential neurotoxicity have attracted the attention of neuroscientists. Microglia play important roles in the inflammatory process and in neuromodulation of the central nervous system. Microglia-mediated neuroinflammation is a key mechanism of neurocognitive dysfunction during the perioperative period. Microglial activation by GAAs induces antiinflammatory and pro-inflammatory effects in microglia, suggesting that GAAs play a dual role in the mechanism of postoperative cognitive dysfunction. Understanding of the mechanisms by which GAAs regulate microglia may help to reduce the incidence of postoperative adverse effects. Here, we review the actions of GAAs on microglia and the consequent changes in microglial function. We summarize clinical and animal studies associating microglia with general anesthesia and describe how GAAs interact with neurons via microglia to further explore the mechanisms of action of GAAs in the nervous system. [ABSTRACT FROM AUTHOR]

Cross-regional technology transfer is an important driving force for achieving the coordinated development of technology resources and breaking down China's provincial technical barriers. Due to the imbalance in China's technology development level, it is difficult to achieve comprehensive revitalization policies. Therefore, improving the efficiency of technology transfer is an effective way to solve this problem. This paper selects the relevant data of 31 provinces and regions in China in 2019 for analysis, uses factor analysis to measure the efficiency of technology transfer, and then proposes a technology transfer improvement path through QCA clear set configuration analysis. The study found that the development of technology transfer efficiency in 31 provinces and regions in China is extremely unbalanced. The improvement paths that effectively break this unbalanced development status can be summarized into 4 types, namely, the "intermediary-environment" leading path, weak "intermediary-R&D-environment" leading path, strong "intermediary-R&D-environment" leading path and "intermediary-economic" leading path. [ABSTRACT FROM AUTHOR]