Phase Separation Enhanced PROTAC for Highly Efficient Protein Degradation.

Biomacromolecular condensates formed via phase separation establish compartments for the enrichment of specific compositions, which is also used as a biological tool to enhance molecule condensation, thereby increasing the efficiency of biological processes. Proteolysis-targeting chimeras (PROTACs) have been developed as powerful tools for targeted protein degradation in cells, offering a promising approach for therapies for different diseases. Herein, we introduce an intrinsically disordered region in the PROTAC (denoted PSETAC), which led to the formation of droplets of target proteins in the cells and increased degradation efficiency compared with PROTAC without phase separation. Further, using a nucleus targeting intrinsically disordered domain, the PSETAC was able to target and degrade nuclear-located proteins. Finally, we demonstrated intracellular delivery of PSETAC using lipid nanoparticle-encapsulated mRNA (mRNA-LNP) for the degradation of the endogenous target protein. This study established the PSETAC mRNA-LNP method as a potentially translatable, safe therapeutic strategy for the development of clinical applications based on PROTAC.

Atypical dynamic neural configuration in autism spectrum disorder and its relationship to gene expression profiles.

Although it is well recognized that autism spectrum disorder (ASD) is associated with atypical dynamic functional connectivity patterns, the dynamic changes in brain intrinsic activity over each time point and the potential molecular mechanisms associated with atypical dynamic temporal characteristics in ASD remain unclear. Here, we employed the Hidden Markov Model (HMM) to explore the atypical neural configuration at every scanning time point in ASD, based on resting-state functional magnetic resonance imaging (rs-fMRI) data from the Autism Brain Imaging Data Exchange. Subsequently, partial least squares regression and pathway enrichment analysis were employed to explore the potential molecular mechanism associated with atypical neural dynamics in ASD. 8 HMM states were inferred from rs-fMRI data. Compared to typically developing, individuals on the autism spectrum showed atypical state-specific temporal characteristics, including number of states and occurrences, mean life time and transition probability between states. Moreover, these atypical temporal characteristics could predict communication difficulties of ASD, and states assoicated with negative activation in default mode network and frontoparietal network, and positive activation in somatomotor network, ventral attention network, and limbic network, had higher predictive contribution. Furthermore, a total of 321 genes was revealed to be significantly associated with atypical dynamic brain states of ASD, and these genes are mainly enriched in neurodevelopmental pathways. Our study provides new insights into characterizing the atypical neural dynamics from a moment-to-moment perspective, and indicates a linkage between atypical neural configuration and gene expression in ASD.

Differential signaling effects of blood glucose on delay discounting in individuals with and without type 1 diabetes.

Based on the signaling hypothesis of blood glucose (BG), a rise in BG levels signals a positive energy budget for healthy individuals but cellular starvation for individuals with type 1 diabetes. We examined this novel prediction and its intervention implications in the context of delay discounting, the degree to which delayed rewards are discounted, and the regulatory effects of insulin ingestion. We recruited 44 adults with type 1 diabetes (mean age 30.8 years, diabetes duration 15.4 years) and recorded their BG levels. The delay discounting rate was measured using the intertemporal choice task, where participants were required to choose between sets of smaller-and-sooner (SS) and larger-and-later (LL) rewards. In addition, 82 age-matched healthy participants were recruited to provide a baseline comparison on delay discounting. Random forest analysis showed that among many diagnostic factors, delay discounting was most dominating in differentiating the individuals with type 1 diabetes from the control participants. A hierarchical linear mixed model revealed that participants with type 1 diabetes had a stronger preference for SS rewards (p < .001) after controlling for covariates. Participants who had insulin delivered before the last meal exhibited a stronger preference for LL rewards compared to after-meal delivery. In contrast, subjective measures (e.g., self-reported hunger) failed to predict the participants' actual BG levels and delay discounting rates. In sum, individuals with type 1 diabetes tend to discount future rewards excessively compared to the control participants. Pre-meal insulin ingestion was associated with a higher LL preference for future rewards.

Brain development of a school-aged boy with autism spectrum condition talented in arithmetic: a case report.

Whereas autism spectrum condition is known for its social and communicative challenges, some autistic children demonstrate unusual islets of abilities including those related to mathematics, the neurobiological underpinnings of which are increasingly becoming the focus of research. Here we describe an 8-year-old autistic boy with intellectual and language challenges, yet exceptional arithmetic ability. He can perform verbal-based multiplication of three- and even four-digit numbers within 20 seconds. To gain insights into the neural basis of his talent, we investigated the gray matter in the child's brain in comparison to typical development, applying voxel-based morphometry to magnetic resonance imaging data. The case exhibited reduced gray matter volume in regions associated with arithmetic, which may suggest an accelerated development of brain regions with arithmetic compared to typically developing individuals: potentially a key factor contributing to his exceptional talent. Taken together, this case report describes an example of the neurodiversity of autism. Our research provides valuable insights into the potential neural basis of exceptional arithmetic abilities in individuals with the autism spectrum and its potential contribution to depicting the diversity and complexity of autism.

Acupoint Autohemotherapy Attenuates DNCB-Induced Atopic Dermatitis and Activates Regulatory T Cells in BALB/c Mice.

Purpose: Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown. Methods: This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10+, IFN-γ+ and FoxP3+CD4+T cells in murine spleen. Results: It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3+, IL-10+ and IFN-γ+ CD4+T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation. Conclusion: These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.

SERS Detection of Trace Carcinogenic Aromatic Amines Based on Amorphous MoO3 Monolayers.

Aromatic amines are important commercial chemicals, but their carcinogenicity poses a threat to humans and other organisms, making their rapid quantitative detection increasingly urgent. Here, amorphous MoO3 (a-MoO3) monolayers with localized surface plasmon resonance (LSPR) effect in the visible region are designed for the trace detection of carcinogenic aromatic amine molecules. The hot-electron fast decay component of a-MoO3 decreases from 301 fs to 150 fs after absorption with methyl orange (MO) molecules, indicating the plasmon-induced hot-electron transfer (PIHET) process from a-MoO3 to MO. Therefore, a-MoO3 monolayers present high SERS performance due to the synergistic effect of electromagnetic enhancement (EM) and PIHET, proposing the EM-PIHET synergistic mechanism in a-MoO3. In addition, a-MoO3 possesses higher electron delocalization and electronic state density than crystal MoO3 (c-MoO3), which is conducive to the PIHET. The limit of detection (LOD) for o-aminoazotoluene (o-AAT) is 10-9 M with good uniformity, acid resistance, and thermal stability. In this work, trace detection and identification of various carcinogenic aromatic amines based on a-MoO3 monolayers is realized, which is of great significance for reducing cancer infection rates.

ESF-YOLO: an accurate and universal object detector based on neural networks.

As an excellent single-stage object detector based on neural networks, YOLOv5 has found extensive applications in the industrial domain; however, it still exhibits certain design limitations. To address these issues, this paper proposes Efficient Scale Fusion YOLO (ESF-YOLO). Firstly, the Multi-Sampling Conv Module (MSCM) is designed, which enhances the backbone network's learning capability for low-level features through multi-scale receptive fields and cross-scale feature fusion. Secondly, to tackle occlusion issues, a new Block-wise Channel Attention Module (BCAM) is designed, assigning greater weights to channels corresponding to critical information. Next, a lightweight Decoupled Head (LD-Head) is devised. Additionally, the loss function is redesigned to address asynchrony between labels and confidences, alleviating the imbalance between positive and negative samples during the neural network training. Finally, an adaptive scale factor for Intersection over Union (IoU) calculation is innovatively proposed, adjusting bounding box sizes adaptively to accommodate targets of different sizes in the dataset. Experimental results on the SODA10M and CBIA8K datasets demonstrate that ESF-YOLO increases Average Precision at 0.50 IoU (AP50) by 3.93 and 2.24%, Average Precision at 0.75 IoU (AP75) by 4.77 and 4.85%, and mean Average Precision (mAP) by 4 and 5.39%, respectively, validating the model's broad applicability.

Hidden Real Topology and Unusual Magnetoelectric Responses in Two-Dimensional Antiferromagnets.

Recently, the real topology has been attracting widespread interest in two dimensions (2D). Here, based on first-principles calculations and theoretical analysis, the monolayer Cr2Se2O (ML-CrSeO) is revealed as the first material example of a 2D antiferromagnetic (AFM) real Chern insulator (RCI) with topologically protected corner states. Unlike previous RCIs, it is found that the real topology of the ML-CrSeO is rooted in one certain mirror subsystem of the two spin channels, and cannot be directly obtained from all the valence bands in each spin channel as commonly believed. In particular, due to antiferromagnetism, the corner modes in ML-CrSeO exhibit strong corner-contrasted spin polarization, leading to spin-corner coupling (SCC). This SCC enables a direct connection between spin space and real space. Consequently, large and switchable net magnetization can be induced in the ML-CrSeO nanodisk by electrostatic means, such as potential step and in-plane electric field, and the corresponding magnetoelectric responses behave like a sign function, distinguished from that of the conventional multiferroic materials. This work considerably broadens the candidate range of RCI materials, and opens up a new direction for topo-spintronics and 2D AFM materials research.

Disulfiram Improves Fat Graft Retention by Modulating Macrophage Polarization Via Inhibition of NLRP3 Inflammasome-Mediated Pyroptosis.

BACKGROUND: Macrophage-mediated inflammatory response in the early post-grafting period restricts fat graft retention. Pyroptosis is a novel type of programmed cell death that extensively participates in inflammatory pathologies. OBJECTIVES: This study sought to determine whether macrophage pyroptosis is activated during the inflammatory phase after fat grafting and to investigate the efficacy of a pyroptosis inhibitor, disulfiram (DSF) in fat graft retention. METHODS: We established a C57BL/6 mice fat grafting model and then analyzed macrophage pyroptosis. DSF (50 mg/kg, every other day) was intraperitoneally injected started from 1 h prior to fat grafting and continued for 14 days. An in vitro co-culture system was established in which mouse RAW264.7 macrophages were co-cultured with apoptotic adipocytes to further validate the findings of the in vivo studies and to explore the underlying mechanisms. RESULTS: Here we reported that macrophage pyroptosis was activated in both fat grafts and in vitro co-culture models. DSF was found to be a potent pyroptosis inhibitor to promote M2 macrophage polarization. In addition, DSF was demonstrated to enhance vascularization and graft retention. CONCLUSIONS: Our results suggested that pyroptosis plays a crucial role in the inflammatory cascade within fat grafts. DSF, being a clinically available drug could be translated into a clinically effective drug for improving fat graft survival via inhibiting macrophage pyroptosis, thereby inducing M2 macrophage polarization and promoting neovascularization.

Bi2WO6/TiO2-based visible light-driven photoelectrochemical enzyme biosensor for glucose measurement.

Nowadays, the frequent occurrence of food adulteration makes glucose detection particularly important in food safety and quality management. The quality and taste of honey are closely related to the glucose content. However, due to the drawbacks of expensive equipment, complex operating procedures, and time-consuming processes, the application scope of traditional glucose detection methods is limited. Hence, this study developed a photoelectric chemical (PEC) sensor, which is composed of a photoactive material of bismuth tungstate (Bi2WO6) with titanium dioxide (TiO2) and glucose oxidase (GOD), for simple and rapid detection of glucose. Notably, the composites' absorption prominently increased in the visible light region, and the photo-generated electron-hole pairs were efficiently separated by virtue of the unique nanostructure system, thus playing a crucial role in facilitating PEC activity. In the presence of dissolved oxygen, the photocurrent intensity was enhanced by H2O2 generated from glucose under electro-oxidation specifically catalyzed by GOD fixed on the modified electrode. When the working potential was 0.3 V, the changes of photocurrent response indicated that the PEC enzyme biosensor provides a low detection limit (3.8 µM), and a wide linear range (0.008-8 mM). This method has better selectivity in honey samples and broad application prospects in clinical diagnosis for future.

Impact of early rehabilitation therapy on functional outcomes in patients post distal radius fracture surgery: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis aims to investigate the efficacy of early rehabilitation on patients who have undergone surgery for distal radius fractures (DRFs) with palmar plating, focusing on multiple outcome measures including upper limb function, wrist function, back extension mobility, pain levels, and complications. METHODS: A rigorous search strategy adhering to the PRISMA guidelines was employed across four major databases, including PubMed, Embase, Web of Science, and the Cochrane Library. Studies were included based on stringent criteria, and data extraction was performed independently by two reviewers. Meta-analysis was conducted employing both fixed-effect and random-effects models as dictated by heterogeneity, assessed by the I2 statistic and chi-square tests. A total of 7 studies, encompassing diverse demographic groups and timelines, were included for the final analysis. RESULTS: The meta-analysis disclosed that early rehabilitation yielded a statistically significant improvement in upper limb function (SMD -0.27; 95% CI -0.48 to -0.07; P < 0.0001) and back extension mobility (SMD 0.26; 95% CI 0.04 to 0.48; P = 0.021). A notable reduction in pain levels was observed in the early rehabilitation group (SMD -0.28; 95% CI -0.53 to -0.02; P = 0.03). However, there were no significant differences in wrist function (SMD -0.13; 95% CI -0.38 to 0.12; P = 0.36) and complications (OR 0.99; 95% CI 0.61 to 1.61; P = 0.96). CONCLUSIONS: Early rehabilitation post-DRF surgery with palmar plating has been found to be beneficial in enhancing upper limb functionality and back extension mobility, and in reducing pain levels. Nevertheless, no significant impact was observed regarding wrist function and complications.

Correlation of levels of lactic acid and glucose in cerebrospinal fluid of cerebral hemorrhage patients with the occurrence of postoperative intracranial infection and clinical prognosis.

Background: Cerebral haemorrhage is a critical condition that often requires surgical treatment, and postoperative intracranial infection can significantly impact patient outcomes. The aim of the study was to examine the relationship between the levels of lactic acid and glucose in cerebrospinal fluid (CSF) of patients with cerebral haemorrhage and their postoperative intracranial infection and clinical prognosis. Methods: The study selected the clinical data of 324 patients with cerebral haemorrhage who underwent surgical treatment in our hospital from March 2020 to March 2022 for retrospective analysis and divided these patients into the intracranial infection group (Group A, n=22, leukocyte values in CSF>5×106/L) and the non-intracranial infection group (Group B, n=302, leukocyte values in CSF 5×106/L) according to the occurrence of postoperative intracranial infection in patients to detect the levels of lactic acid and glucose in CSF at different times in the two groups. Pearson method was adopted to analyze the correlation of the levels of lactic acid and glucose in CSF of patients with intracranial infection, and the Glasgow Outcome Scale (GOS) was used to assess the clinical prognosis of patients. According to their scores, these patients were divided into the good prognosis group (GPG, scores of 4-5 points, n=178) and the poor prognosis group (PPG, scores of 1-3 points, n=146). The levels of lactic acid and glucose in the CSF of patients in the two groups were measured, and the Pearson method was adopted to analyze the relationship between these levels and clinical prognosis.

Effects of Nanobubbles on Photochemical Processes of Levofloxacin Photosensitizer.

Photodynamic therapy (PDT) stands as an efficacious modality for the treatment of cancer and various diseases, in which optimization of the electron transfer and augmentation of the production of lethal reactive oxygen species (ROS) represent pivotal challenges to enhance its therapeutic efficacy. Empirical investigations have established that the spontaneous initiation of redox reactions associated with electron transfer is feasible and is located in the gas-liquid interfaces. Meanwhile, nanobubbles (NBs) are emerging as entities capable of furnishing a plethora of such interfaces, attributed to their stability and large surface/volume ratio in bulk water. Thus, NBs provide a chance to expedite the electron-transfer kinetics within the context of PDT in an ambient environment. In this paper, we present a pioneering exploration into the impact of nitrogen nanobubbles (N2-NBs) on the electron transfer of the photosensitizer levofloxacin (LEV). Transient absorption spectra and time-resolved decay spectra, as determined through laser flash photolysis, unequivocally reveal that N2-NBs exhibit a mitigating effect on the decay of the LEV excitation triplet state, thereby facilitating subsequent processes. Of paramount significance is the observation that the presence of N2-NBs markedly accelerates the electron transfer of LEV, albeit with a marginal inhibitory influence on its energy-transfer reaction. This observation is corroborated through absorbance measurements and offers compelling evidence substantiating the role of NBs in expediting electron transfer within the ambit of PDT. The mechanism elucidated herein sheds light on how N2-NBs intricately influence both electron-transfer and energy-transfer reactions in the photosensitizer LEV. These findings not only contribute to a nuanced understanding of the underlying processes but also furnish novel insights that may inform the application of NBs in the realm of photodynamic therapy.

Facet-dependent activation of oxalic acid over hematite nanocrystals under the irradiation of visible light for efficient degradation of pollutants.

Naturally occurring hematite has been widely studied in the Fenton-like system for water pollutant remediation due to its abundance and non-toxicity. However, its inadequate catalytic activity results in difficulty in effectively degrading pollutants in the catalytic degradation system that it constitutes. Thus, we constructed a photochemical system composed of hematite with {001} facet of high activity facet and low-cost and non-toxic oxalic acid (OA) for the removal of various types of pollutants. The removal rate for the degradation of metronidazole, tetracycline hydrochloride, Rhodamine B, and hexavalent chromium by hematite nanoplate with the exposed {001} facet activating OA under visible light irradiation was 4.75, 2.25, 2.33, and 2.74 times than that by the exposed {110} facet, respectively. Density functional theory (DFT) calculation proved that the OA molecule was more easily adsorbed on the {001} facet of hematite than that on the {110} facet, which would favor the formation of the more Fe(III)-OA complex and reactive species. In addition, the reactive site of metronidazole for the attraction of radicals was identified on the basis of the DFT calculation on the molecular occupied orbitals, and the possible degradation pathway for metronidazole included carbon chain fracture, hydroxyethyl-cleavage, denitrogenation, and hydroxylation. Thus, this finding may offer a valuable direction in designing an efficient iron-based catalyst based on facet engineering for the improved activity of Fenton-like systems such as OA activation.

Genetic control of thermomorphogenesis in tomato inflorescences.

Understanding how plants alter their development and architecture in response to ambient temperature is crucial for breeding resilient crops. Here, we identify the quantitative trait locus qMULTIPLE INFLORESCENCE BRANCH 2 (qMIB2), which modulates inflorescence branching in response to high ambient temperature in tomato (Solanum lycopersicum). The non-functional mib2 allele may have been selected in large-fruited varieties to ensure larger and more uniform fruits under varying temperatures. MIB2 gene encodes a homolog of the Arabidopsis thaliana transcription factor SPATULA; its expression is induced in meristems at high temperature. MIB2 directly binds to the promoter of its downstream gene CONSTANS-Like1 (SlCOL1) by recognizing the conserved G-box motif to activate SlCOL1 expression in reproductive meristems. Overexpressing SlCOL1 rescue the reduced inflorescence branching of mib2, suggesting how the MIB2-SlCOL1 module helps tomato inflorescences adapt to high temperature. Our findings reveal the molecular mechanism underlying inflorescence thermomorphogenesis and provide a target for breeding climate-resilient crops.

Mechanism of effect of stenting on hemodynamics at iliac vein bifurcation.

When performing stent intervention for iliac vein compression syndrome, the operator selects the appropriate stent and determines its implantation depth according to the type and severity of iliac vein stenosis in the patient. However, there is still uncertainty regarding how the structure of the stent and its implantation depth affect hemodynamics at the site of lesion. In this paper, we analyzed three commonly used stents (Vena stent from Venmedtch, Venovo from Bard, and Smart stent from Cordis) with different implantation depths (0, 10, 20 mm) using computational fluid dynamics (CFD). We focused on evaluating hemorheological parameters such as time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), etc., within one pulsatile cycle after stent implantation. The correlation between geometric parameters of the stents and hemodynamic indicators was assessed using Pearson correlation coefficient (r), which was further validated through PIV velocity measurement experiment. The results revealed that an increase in implantation depth led to a more pronounced disturbance effect on blood flow at bifurcation for densely arranged support body-type stents. This effect was particularly significant during periods of smooth blood flow. On the other hand, crown-shaped Vena stents exhibited relatively less disruption to blood flow post-implantation. Implantation depth showed a strong negative correlation with TAWSS but a strong positive correlation with OSI and RRT. These findings suggest an increased risk of thrombosis at iliac vein bifurcation following stent placement. Amongst all three tested stents, Vena Stent demonstrated more favorable periodic parameters after implantation compared to others. These results provide valuable theoretical insights into understanding contralateral circulation thrombosis associated with iliac vein stenting.

N6-Methyladenosine Modification of lncCCKAR-5 Regulates Autophagy in Human Umbilical Cord Mesenchymal Stem Cells by Destabilizing LMNA and Inhibits Diabetic Wound Healing.

Long noncoding RNAs are pivotal contributors to the development of human diseases. However, their significance in the context of diabetic wound healing regulated by human umbilical cord mesenchymal stem cells (hUCMSCs) remains unclear. This study sheds light on the involvement of lncCCKAR5 in this process. We found that hUCMSCs exposed to high glucose conditions exhibited a significant downregulation of lncCCKAR5 expression, and lncCCKAR5 played a critical role in modulating autophagy, thus inhibiting apoptosis in hUCMSCs. In addition, the reduction of lncCCKAR5 in cells exposed to high glucose effectively thwarted cellular senescence and facilitated filopodium formation. Mechanistically, lncCCKAR5 served as a scaffold that facilitated the interaction between MKRN2 and LMNA, a key regulator of cytoskeletal function and autophagy. The lncCCKAR5/LMNA/MKRN2 complex played a pivotal role in promoting the ubiquitin-mediated degradation of LMNA, with this effect being further augmented by N6-adenosine methylation of lncCCKAR5. Consequently, our findings underscore the critical role of lncCCKAR5 in regulating the autophagic process in hUCMSCs, particularly through protein ubiquitination and degradation. This intricate regulatory network presents a promising avenue for potential therapeutic interventions in the context of diabetic wound healing involving hUCMSCs.

Prediction of a two-dimensional high Curie temperature Weyl nodal line kagome semimetal.

Kagome lattices may have numerous exotic physical properties, such as stable ferromagnetism and topological states. Herein, combining the particle swarm structure search method with first-principles calculations, we identify a two-dimensional (2D) kagome Mo2Se3 crystal structure with space group P6/mmm. The results show that 2D kagome Mo2Se3 is a 100% spin-polarized topological nodal line semimetal and exhibits excellent ambient stability. The band crossing points form two nodal loops around the high-symmetry points Γ and K. On the other hand, Mo2Se3 shows intrinsic ferromagnetism with a large magnetic moment of 3.05 µB per Mo atom and magnetic anisotropy energy (MAE) of 4.78 meV. Monte Carlo simulations estimate that Mo2Se3 possesses a high Curie temperature of about 673 K. In addition, its ferromagnetic ground state can be well preserved under external strain, and the MAE can be improved by increasing the strain. More importantly, the position of each nodal line can be adjusted to the Fermi level through hole doping. This multifunctional 2D magnetic material that combines spin and topology has great potential in the field of nanoscale spintronic devices.

Transmission-Constrained Consensus Over Random Graphs.

The exchange of information is a crucial factor in achieving consensus among agents. However, in real-world scenarios, nonideal information sharing is prevalent due to complex environmental conditions. Consider the information distortions (data) and stochastic information flow (media) during state transmission both caused by physical constraints, a novel model of transmission-constrained consensus over random networks is proposed in this work. The transmission constraints are represented by heterogeneous functions that reflect the impact of environmental interference in multiagent systems or social networks. A directed random graph is applied to model the stochastic information flow where every edge is connected probabilistically. Using stochastic stability theory and the martingale convergence theorem, it is demonstrated that the agent states will converge to a consensus value with probability 1, despite information distortions and randomness in information flow. Numerical simulations are presented to validate the effectiveness of the proposed model.

Alternative cleavage and polyadenylation of the Ccnb1 mRNA defines accumulation of cyclin protein during the meiotic cell cycle.

Progression through the mitotic and meiotic cell cycle is driven by fluctuations in the levels of cyclins, the regulatory subunits controlling the localization and activity of CDK1 kinases. Cyclin levels are regulated through a precise balance of synthesis and degradation. Here we demonstrate that the synthesis of Cyclin B1 during the oocyte meiotic cell cycle is defined by the selective translation of mRNA variants generated through alternative cleavage and polyadenylation (APA). Using gene editing in mice, we introduced mutations into the proximal and distal polyadenylation elements of the 3' untranslated region (UTR) of the Ccnb1 mRNA. Through in vivo loss-of-function experiments, we demonstrate that the translation of mRNA with a short 3' UTR specifies Cyclin B1 protein levels that set the timing of meiotic re-entry. In contrast, translation directed by a long 3' UTR is necessary to direct Cyclin B1 protein accumulation during the MI/MII transition. These findings establish that the progression through the cell cycle is dependent on the selective translation of multiple mRNA variants generated by APA.