Pinning Synchronization for Stochastic Complex Networks With Randomly Occurring Nonlinearities: Tackling Bit Rate Constraints and Allocations.

In this article, the ultimately bounded synchronization problem is investigated for a class of discrete-time stochastic complex networks under the pinning control strategy. Communication between system nodes and the remote controller is facilitated via wireless networks subject to bit rate constraints. The system model is distinguished by the inclusion of randomly occurring nonlinearities. A coding-decoding transmission mechanism under constrained bit rates is introduced to characterize the digital transmission process. To achieve synchronization of the network nodes with the unforced target node, a pinning controller is specifically devised based on the information from partially selected nodes. Through the application of the stochastic analysis method, a sufficient condition is derived for ensuring the mean-square boundedness of the synchronization error system. In addition, an optimization algorithm is introduced to address bit rate allocation and the design of desired controller gains. Within the presented theoretical framework, the correlation between the mean-square synchronization performance and bit rate allocation is further elucidated. To conclude, a simulation example is provided to substantiate the efficacy of the recommended pinning control approach.

Loss of Cisd2 Exacerbates the Progression of Age-Related Hearing Loss.

Age-related hearing loss (ARHL) is a disease that impacts human quality of life and contributes to the progression of other neuronal problems. Various stressors induce an increase in free radicals, destroy mitochondria to further contribute to cellular malfunction, and compromise cell viability, ultimately leading to functional decline. Cisd2, a master gene for Marfan syndrome, plays an essential role in maintaining mitochondrial integrity and functions. As shown by our data, specific deletion of Cisd2 in the cochlea exacerbated the hearing impairment of ARHL in C57BL/6 mice. Increased defects in mitochondrial function, potassium homeostasis and synapse activity were observed in the Cisd2-deleted mouse models. These mechanistic phenotypes combined with oxidative stress contribute to cell death in the whole cochlea. Human patients with obviously deteriorated ARHL had low Cisd2 expression; therefore, Cisd2 may be a potential target for designing therapeutic methods to attenuate the disease progression of ARHL.

A Homozygous Variant in NAA60 Is Associated with Primary Familial Brain Calcification.

BACKGROUND: Primary familial brain calcification (PFBC) is a monogenic disorder characterized by bilateral calcifications in the brain. The genetic basis remains unknown in over half of the PFBC patients, indicating the existence of additional novel causative genes. NAA60 was a recently reported novel causative gene for PFBC. OBJECTIVE: The aim was to identify the probable novel causative gene in an autosomal recessive inherited PFBC family. METHODS: We performed a comprehensive genetic study on a consanguineous Chinese family with 3 siblings diagnosed with PFBC. We evaluated the effect of the variant in a probable novel causative gene on the protein level using Western blot, immunofluorescence, and coimmunoprecipitation. Possible downstream pathogenic mechanisms were further explored in gene knockout (KO) cell lines and animal models. RESULTS: We identified a PFBC co-segregated homozygous variant of c.460_461del (p.D154Lfs*113) in NAA60. Functional assays showed that this variant disrupts NAA60 protein localization to Golgi and accelerated protein degradation. The mutant NAA60 protein alters its interaction with the PFBC-related proteins PiT2 and XPR1, affecting intracellular phosphate homeostasis. Further mass spectrometry analysis in NAA60 KO cell lines revealed decreased expression of multiple brain calcification-associated proteins, including reduced folate carrier (RFC), a folate metabolism-related protein. CONCLUSIONS: Our study replicated the identification of NAA60 as a novel causative gene for autosomal recessive PFBC, demonstrating our causative variant leads to NAA60 loss of function. The NAA60 loss of function disrupts not only PFBC-related proteins (eg, PiT2 and XPR1) but also a wide range of other brain calcification-associated membrane protein substrates (eg, RFC), and provided a novel probable pathogenic mechanism for PFBC. © 2024 International Parkinson and Movement Disorder Society.

Nonfragile Impulsive State Estimation for Complex Networks With Markovian Switching Topologies Subject to Limited Bit Rate Constraints.

In this article, we consider the impulsive estimation problem for a specific category of discrete-time complex networks (CNs) characterized by Markovian switching topologies. The measurement outputs of the underlying CNs, transmitted to the observer over wireless networks, are subject to bit rate constraints. To effectively reduce the estimation error and enhance estimation performance, a mode-dependent impulsive observer is proposed that employs the impulse mechanism. The application of stochastic analysis techniques leads to the derivation of a sufficient condition for ensuring the mean-square boundedness of the estimation error dynamics. The upper bound of the error is then analyzed by iteratively exploring the Lyapunov relation at both impulsive and non-impulsive instants. Moreover, an optimization algorithm is presented for handling the bit rate allocation, which is coupled with the design of desired observer gains using the linear matrix inequality (LMI) approach. Within this theoretical framework, the relationship between the mean-square estimation performance and the bit rate allocation protocol is further elucidated. Finally, a simulation example is provided to demonstrate the validity and effectiveness of the proposed impulsive estimation approach.

State Estimation for Markovian Jump Neural Networks Under Probabilistic Bit Flips: Allocating Constrained Bit Rates.

In this article, the state estimation problem is studied for Markovian jump neural networks (MJNNs) within a digital network framework. The wireless communication channel with limited bandwidth is characterized by a constrained bit rate, and the occurrence of bit flips during wireless transmission is mathematically modeled. A transmission mechanism, which includes coding-decoding under bit-rate constraints and considers probabilistic bit flips, is introduced, providing a thorough characterization of the digital transmission process. A mode-dependent remote estimator is designed, which is capable of effectively capturing the internal state of the neural network. Furthermore, a sufficient condition is proposed to ensure the estimation error to remain bounded under challenging network conditions. Within this theoretical framework, the relationship between the neural network's estimation performance and the bit rate is explored. Finally, a simulation example is provided to validate the theoretical findings.

Changes of heavy metal concentrations in farmland soils affected by non-ferrous metal smelting in China: A meta-analysis.

Long-term human smelting activities have resulted in substantial heavy metals (HMs) pollution of farmland soils around smelting sites, and the safety of farmland products is critical for human health. The current study focuses on HMs in farmland soils surrounding a single smelter, therefore the impact of smelting on a national scale needs to be investigated further. This study was based on 116 papers and 1143 sets of relevant data for meta-analysis, and a hierarchical mixed-effects model was used to quantify the changes of HMs concentrations in farmland soils affected by non-ferrous metal smelting on a national scale, as well as their relationships with relevant explanatory variables in China. Results showed that: (i) non-ferrous metal smelting substantially increased farmland soils HMs concentrations (323%), with each HM concentration increasing in the following order: Cd (2753%) > Pb (562%) > Hg (455%) > Zn (228%) > Cu (158%) > As (107%) > Ni (52%); (ii) the highest increase of HMs in vegetable fields (361%), but not significant in comparison to other farmland categories, and the increase of Pb, Zn, Cu and As concentrations were significantly different in different types of smelting areas; (iii) the increase of Hg was significantly higher in the northern region than in the southern region, and the opposite increase of Cu; (iv) the soil depth from 0 to 40 cm was significantly affected by smelting, and the increase of multiple HMs were significantly positively correlated with soil pH and negatively correlated with distance; (v) the other explanatory variables (farmland category and soil organic matter) were not significantly related to the effect of smelting. The results can provide some reference for protecting and restoring farmland soils around smelting areas.

Bounded synchronization for uncertain master-slave neural networks: An adaptive impulsive control approach.

This paper investigates the bounded synchronization of the discrete-time master-slave neural networks (MSNNs) with uncertainty. To deal with the unknown parameter in the MSNNs, a parameter adaptive law combined with the impulsive mechanism is proposed to improve the estimation efficiency. Meanwhile, the impulsive method also is applied to the controller design for saving the energy. In addition, a novel time-varying Lyapunov functional candidate is employed to depict the impulsive dynamical characteristic of the MSNNs, wherein a convex function related to the impulsive interval is used to obtain a sufficient condition for bounded synchronization of the MSNNs. Based on the above condition, the controller gain is calculated utilizing an unitary matrix. An algorithm is proposed to reduce the boundary of the synchronization error by optimizing its parameters. Finally, a numerical example is provided to illustrate the correctness and the superiority of the developed results.

Frizzled 7 modulates goblet and Paneth cell fate, and maintains homeostasis in mouse intestine.

Intestinal homeostasis depends on interactions between the intestinal epithelium, the immune system and the microbiota. Because of these complicated connections, there are many problems that need to be solved. Current research has indicated that genes targeted by Wnt signaling are responsible for controlling intestinal stem cell fate and for modulating intestinal homeostasis. Our data show that loss of frizzled 7 (Fzd7), an important element in Wnt signaling, interrupts the differentiation of mouse intestinal stem cells into absorptive progenitors instead of secretory progenitors (precursors of goblet and Paneth cells). The alteration in canonical Wnt and Notch signaling pathways interrupts epithelial homeostasis, resulting in a decrease in physical protection in the intestine. Several phenotypes in our Fzd7-deleted model were similar to the features of enterocolitis, such as shortened intestines, decreased numbers of goblet cells and Paneth cells, and severe inflammation. Additionally, loss of Fzd7 exacerbated the defects in a chemical-induced colitis model and could initiate tumorigenesis. These findings may provide important information for the discovery of efficient therapeutic methods to treat enterocolitis and related cancers in the intestines.

Molecular Basis for Luteolin as a Natural TatD DNase Inhibitor in Trueperella pyogenes.

TatD960 and TatD825 are DNases that contribute to biofilm formation and virulence in Trueperella pyogenes (T. pyogenes). Luteolin is a natural flavonoid commonly found in plants that exhibits antimicrobial capacity. Our study aims to investigate the effects of luteolin on TatD DNases as a natural inhibitor. In this research, the expression of tatD genes and TatD proteins in T. pyogenes treated with luteolin was detected, and then the effect of luteolin on the hydrolysis of DNA by TatD DNases was analyzed using agarose gel electrophoresis. Moreover, the interactions between luteolin and TatD DNases were tested using surface plasmon resonance (SPR) assays and molecular docking analysis. After 1/2 MIC luteolin treatment, the transcription of tatD genes and expression of TatD proteins appeared to be reduced in 80-90% of T. pyogenes (n = 20). The gel assay revealed that luteolin can inhibit the activity of TatD DNases. The SPR assay showed that the KD values of luteolin to TatD960 and TatD825 were 6.268 × 10-6 M and 5.654 × 10-6 M, respectively. We found through molecular docking that hydrogen bonding is predominant in the interaction of luteolin and TatD DNases. Our data indicate that luteolin inhibited the ability of TatD DNases by decreasing their binding to DNA. The current study provides an insight into the development of luteolin as a DNase inhibitor in preventing biofilm formation and virulence in T. pyogenes.

Luteolin increases susceptibility to macrolides by inhibiting MsrA efflux pump in Trueperella pyogenes.

Trueperella pyogenes (T. pyogenes) is an opportunistic pathogen associated with a variety of diseases in many domestic animals. Therapeutic treatment options for T. pyogenes infections are becoming limited due to antimicrobial resistance, in which efflux pumps play an important role. This study aims to evaluate the inhibitory activity of luteolin, a natural flavonoid, on the MsrA efflux pump and investigate its mechanism. The results of antimicrobial susceptibility testing indicated that the susceptibility of msrA-positive T. pyogenes isolates to six macrolides increased after luteolin treatment, while the susceptibility of msrA-negative isolates showed no change after luteolin treatment. It is suspected that luteolin may increase the susceptibility of T. pyogenes isolates by inhibiting MsrA activity. After 1/2 MIC luteolin treatment for 36 h, the transcription level of the msrA gene and the expression level of the MsrA protein decreased by 55.0-97.7% and 36.5-71.5%, respectively. The results of an affinity test showed that the equilibrium dissociation constant (KD) of luteolin and MsrA was 6.462 × 10-5 M, and hydrogen bonding was predominant in the interaction of luteolin and MsrA. Luteolin may inhibit the ATPase activity of the MsrA protein, resulting in its lack of an energy source. The current study illustrates the effect of luteolin on MsrA in T. pyogenes isolates and provides insight into the development of luteolin as an innovative agent in combating infections caused by antimicrobial-resistant bacteria.

TatD DNases Contribute to Biofilm Formation and Virulence in Trueperella pyogenes.

TatD DNases are conserved proteins in a variety of organisms and are considered potential virulence factors in Plasmodium falciparum and Streptococcus pneumoniae. However, the function of TatD DNases has not yet been determined in Trueperella pyogenes, which causes various infections in animals and leads to economic losses. In this study, we describe the roles of TatD DNases in T. pyogenes (TpTatDs). A bioinformatics analysis was performed to investigate the sequence characteristics of TpTatDs, and then the ability of recombinant TatD proteins to hydrolyze DNA was determined in the presence of divalent cations. Moreover, we constructed tatD-deficient mutants. The biofilms formed by the wild-type and mutant strains were observed under a microscope. The mortality and bacterial load in the spleen of mice infected with the wild-type strain and tatD-deficient mutants were determined to obtain insights into the role of TatDs in the virulence of T. pyogenes. Two TatD DNases were identified in T. pyogenes. They were Mg2+-dependent DNases and exhibited DNA endonuclease activity. Compared with those formed by the parental strain, biofilms formed by mutants showed a significantly reduced thickness and biomass. Moreover, mutants produced a lower bacterial load in the spleen of mice and compromised virulence. Our data indicated that TatD DNases in T. pyogenes are involved in biofilm formation and required for virulence during infections.

Vitamin B Mitigates Thoracic Aortic Dilation in Marfan Syndrome Mice by Restoring the Canonical TGF-ß Pathway.

Thoracic aortic aneurysm (TAA) formation is a multifactorial process that results in diverse clinical manifestations and drug responses. Identifying the critical factors and their functions in Marfan syndrome (MFS) pathogenesis is important for exploring personalized medicine for MFS. Methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) polymorphisms have been correlated with TAA severity in MFS patients. However, the detailed relationship between the folate-methionine cycle and MFS pathogenesis remains unclear. Fbn1C1039G/+ mice were reported to be a disease model of MFS. To study the role of the folate-methionine cycle in MFS, Fbn1C1039G/+ mice were treated orally with methionine or vitamin B mixture (VITB), including vitamins B6, B9, and B12, for 20 weeks. VITB reduced the heart rate and circumference of the ascending aorta in Fbn1C1039G/+ mice. Our data showed that the Mtr and Smad4 genes were suppressed in Fbn1C1039G/+ mice, while VITB treatment restored the expression of these genes to normal levels. Additionally, VITB restored canonical transforming-growth factor ß (TGF-ß) signaling and promoted Loxl1-mediated collagen maturation in aortic media. This study provides a potential method to attenuate the pathogenesis of MFS that may have a synergistic effect with drug treatments for MFS patients.

Recent progress in separation prediction of counter-current chromatography.

As a liquid-liquid partition chromatography, counter-current chromatography has advantages in large sample loading capacity without irreversible adsorption, which has been widely applied in separation and purification fields. The main factors, including partition coefficient, two-phase solvent systems, apparatus, and operating parameters greatly affect the separation process of counter-current chromatography. To promote the applications of counter-current chromatography, it is essential to develop theoretical research to master the principles of counter-current chromatographic separations so as to achieve predictions before laborious trials. In this article, recent progress about separation prediction methods are reviewed from a point of the steady and unsteady state of the mass transfer process of counter-current chromatography and its mass transfer characteristics, and then it is divided into three aspects: prediction of partition coefficient, modeling the thermodynamic process of counter-current chromatography, and modeling the dynamic process of counter-current chromatography.

The Antibacterial Activity and Mechanism of Action of Luteolin Against Trueperella pyogenes.

PURPOSE: This research aimed to investigate the antibacterial activity and potential mechanism of luteolin against T. pyogenes. MATERIALS AND METHODS: The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of luteolin against various T. pyogenes strains. The potential mechanism of action of luteolin was elucidated through testing and analysing the luteolin-induced alterations of T. pyogenes in several aspects, including cell wall, cell membrane, protein expression, nucleic acid content, topoisomerase activity and energy metabolism. RESULTS: The MIC values of luteolin against various T. pyogenes isolates and ATCC19411 were 78 µg/mL. The increased cell membrane permeability, destruction of cell wall integrity and TEM images after exposure to luteolin showed that the cell wall and membrane were damaged. The content of total protein and nucleic acid in T. pyogenes decreased significantly after treatment with luteolin (1/2 MIC) for 12, 24, and 36 h. Moreover, a hypochromic effect was observed in the absorption spectrum of luteolin when deoxyribonucleic acid (DNA) was added. In addition, after treatment with luteolin, a decrease in nicked or relaxed DNA content, which was catalysed by T. pyogenes-isolated DNA topoisomerase, was observed. In addition, the adenosine triphosphate (ATP) content in cells and the activity of succinate dehydrogenase (SDH) both decreased when T. pyogenes was exposed to different concentrations (1/4 MIC, 1/2 MIC, 1 MIC, 2 MIC) of luteolin for 1 h. CONCLUSION: Luteolin showed distinct antibacterial activity against T. pyogenes by multiple actions, which mainly include destroying the integrity of the cell wall and cell membrane, influencing the expression of proteins, inhibiting nucleic acid synthesis, and interfering with energy metabolism.

Nonfragile Finite-Time Synchronization for Coupled Neural Networks With Impulsive Approach.

This article addresses the problem of the average stochastic finite-time synchronization (ASFTS) for a set of coupled neural networks (NNs) with energy-bounded noises. Due to the channel capacity constraint, the impulsive approach is introduced so as to cut down the communication times among the leader NNs and the follower NNs. Then, a nonfragile controller is designed to improve the robustness of the controller with randomly occurred uncertainty. The sufficient conditions that guarantee the ASFTS of the coupled NNs and the leader NNs are achieved. The boundary of the synchronization error is also obtained by constructing the monotonic increasing functions. Finally, the controller gains are given based on the derived conditions, and their effectiveness is illustrated by a numerical example.

Response surface optimization and antioxidant activity of total proanthocyanidins fraction from Abutilon theophrasti Medic. leaves.

The extraction procedure and antioxidant activity were investigated for total proanthocyanidins extracts from Abutilon theophrasti Medic. leaves collected in August, September and October. The maximum extraction yield was achieved with 90% ethanol, 80°C of heating reflux temperature, 149.94 min of extraction time and 60(ml/g) of the ratio of solvent and material, which were optimized by Box-Behnken Design of response surface method. Spectrophotometric study displayed that total proanthocyanidins content was (0.44±0.02)% (0.52±0.01)% and (0.59±0.01)% for August, September and October samples, respectively. The proanthocyanidins extracts exhibited much stronger antioxidant activity to scavenge ABTS and DPPH free radicals, and reduce ferric power than the control synthetic antioxidant BHT. The present findings suggest that the proanthocyanidins extract from Abutilon theophrasti Medic. leaves was a very interesting candidate for the research and development of natural and healthy antioxidant for the pharmaceutical and food industries.

Rrm2b deletion causes mitochondrial metabolic defects in renal tubules.

Renal diseases impose considerable health and economic burdens on health systems worldwide, and there is a lack of efficient methods for the prevention and treatment due to their complexity and heterogeneity. Kidneys are organs with a high demand for energy produced by mitochondria, in which Rrm2b has critical functions as reported. The Rrm2b kidney-specific knockout mice we generated exhibited age-dependent exacerbated features, including mitochondrial dysfunction and increased oxidative stress; additionally, resulted in severe disruption of mitochondria-related metabolism. Rrm2b is vital not only to supply dNTPs for DNA replication and repair, but also to maintain structural integrity and metabolic homeostasis in mitochondria. Thence, Rrm2b deletion might induce chronic kidney defects in mice. This model can facilitate exploration of novel mechanisms and targeted therapies in the kidney diseases and has important translational and clinical implications.

Extraction technology, component analysis, and in vitro antioxidant and antibacterial activities of total flavonoids and fatty acids from Tribulus terrestris L. fruits.

The current study focused on the extraction technology, components analysis, in vitro antioxidant and antibacterial activities of total flavonoids and fatty acids from Tribulus terrestris L. fruits. The extraction process of total flavonoids and fatty acids was optimized by the response surface method, and the compositions were identified from the two extracts by HPLC-DAD-ESI-MS- and GC-MS, respectively. In addition, the antioxidant and antibacterial activities were evaluated by assay of ABTS, DPPH radical scavenging activity, ferric reducing antioxidant power and minimal inhibitory concentration. The yields of total flavonoids and fatty acids were 0.46 and 9.76% under the optimized conditions. Moreover, nine and eight compositions were identified from the two extracts based on the related references, respectively. In addition, total flavonoids and fatty acids extracts both exhibited certain antioxidant and antibacterial activities. The present findings suggest that total flavonoids extracted from T. terrestris L. fruits comprised a more interesting candidate than fatty acids for the research and development of natural and healthy antioxidants and antibacterial agents for the pharmaceutical and food industries.

The protective effect of the flavonoid fraction of Abutilon theophrasti Medic. leaves on LPS-induced acute lung injury in mice via the NF-κB and MAPK signalling pathways.

Accompanied by the damages of epithelial and capillary endothelial cell, acute lung injury is diagnosed with the typical pathological symptoms in clinic, including diffusing of pulmonary interstitial, alveolar oedema and hypoxic respiratory insufficiency. Current study focused on the investigation the anti-inflammatory action and mechanisms of total flavonoids extract (TFE) from Abutilon theophrasti Medic. leaves on ALI mice induced by LPSs. Mice were administrated intragastrically with TFE at the concentrations of 0.25, 0.5, or 1.0 g/kg for 5 days, and on last day, nasal administration of LPSs for 6 h after 30 min for intragastric administration of TFE. Pretreatment with TFE not only reduced oxidative damage but also alleviated lung edema in ALI mice. Increased secretion of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6, caused by LPSs was reversed by TFE; on the contrary, the anti-inflammatory cytokine IL-10 was upregulated. The proteins expressions of pro-inflammatory mediators iNOS and COX-2 induced by LPSs, were down-regulated by TFE. Moreover, the activation of NF-κB and MAPK signalling pathways was inhibited by TFE in LPSs induced ALI mice. The results revealed that the anti-inflammatory mechanisms of TFE were via inhibition of NF-κB and MAPK activation. Combined, the results suggested that TFE might exert in vivo antioxidant and anti-inflammatory functions in LPSs stimulated mice, and will be potential in adjuvant treatment in oxidative stress and inflammation diseases.