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Summary: The cortex and cerebellum form multi-synaptic reciprocal connections. We investigate the functional connectivity between single spiking cerebellar neurons and the population activity of the mouse dorsal cortex using mesoscale imaging. Cortical representations of individual cerebellar neurons vary significantly across different brain states but are drawn from a common set of cortical networks. These cortical-cerebellar connectivity features are observed in mossy fibers and Purkinje cells as well as neurons in different cerebellar lobules, albeit with variations across cell types and regions. Complex spikes of Purkinje cells preferably associate with the sensorimotor cortex, whereas simple spikes display more diverse cortical connectivity patterns. The spontaneous functional connectivity patterns align with cerebellar neurons’ functional responses to external stimuli in a modality-specific manner. The tuning properties of subsets of cerebellar neurons differ between anesthesia and awake states, mirrored by state-dependent changes in their long-range functional connectivity patterns with mesoscale cortical activity.

Brain function originates from hierarchical spatial-temporal neural dynamics distributed across cortical and subcortical networks. However, techniques available to assess large-scale brain network activity with single-neuron resolution in behaving animals remain limited. Here, we present Mesotrode that integrates chronic wide-field mesoscale cortical imaging and compact multi-site cortical/subcortical cellular electrophysiology in head-fixed mice that undergo self-initiated running or orofacial movements. Specifically, we harnessed the flexibility of chronic multi-site tetrode recordings to monitor single-neuron activity in multiple subcortical structures while simultaneously imaging the mesoscale activity of the entire dorsal cortex. A mesoscale spike-triggered averaging procedure allowed the identification of cortical activity motifs preferentially associated with single-neuron spiking. Using this approach, we were able to characterize chronic single-neuron-related functional connectivity maps for up to 60 days post-implantation. Neurons recorded from distinct subcortical structures display diverse but segregated cortical maps, suggesting that neurons of different origins participate in distinct cortico-subcortical pathways. We extended the capability of Mesotrode by implanting the micro-electrode at the facial motor nerve and found that facial nerve spiking is functionally associated with the PTA, RSP, and M2 network, and optogenetic inhibition of the PTA area significantly reduced the facial movement of the mice. These findings demonstrate that Mesotrode can be used to sample different combinations of cortico-subcortical networks over prolonged periods, generating multimodal and multi-scale network activity from a single implant, offering new insights into the neural mechanisms underlying specific behaviors.

Abstract In the digital era, realising intelligent digital transformation is a major challenge in the manufacturing field. Digital transformation means bringing more profit appreciation. To improve the analysis reliability of value‐added processes, this study proposes a method for assessing enterprises value‐adding activities. For this purpose, a hybrid model is constructed based on data and mathematics, bridged by a server. The research builds an element group model that identifies data from different sources, and also gives a mathematical model to describe the relationship of the supply, marketing and service. Taking an automobile manufacturing value chain as an example, to theoretically analyse the composition of value‐added activities. Then, the assembly process of an automobile manufacturing plant was used as a value‐added case study. The simulation results show the impact of changing production layout and product handling angle on the whole value chain. The study can provide new ideas for the intelligent digital transformation of the manufacturing industry.

Breast milk is widely considered to be the most natural, safe, and complete food for infants. However, current breastfeeding rates fall short of the recommendations established by the World Health Organization. Despite this, there are few studies that have focused on the promotion of human lactation through nutrient supplementation. Therefore, the aim of this study was to investigate the effect of methionine on milk synthesis in human mammary epithelial cells (MCF-10A cells) and to explore the underlying mechanisms. To achieve this, MCF-10A cells were cultured with varying concentrations of methionine, ranging from 0 to 1.2 mM. Our results indicated that 0.6 mM of methionine significantly promoted the synthesis of milk protein. An RNA-seq analysis revealed that methionine acted through the PI3K pathway. This finding was validated through real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. In addition, PI3K inhibition assays confirmed that methionine upregulated the expression of both mTOR and p-mTOR through activation of PI3K. Taken together, these findings suggest that methionine positively regulates milk protein synthesis in MCF-10A cells through the PI3K-mTOR signaling pathway.

Purpose: To assess the significance of mutation mutual exclusion information in the optimization of radiomics algorithms for predicting gene mutation.Methods: We retrospectively analyzed 258 non-small cell lung cancer (NSCLC) patients. Patients were randomly divided into training (n = 180) and validation (n = 78) cohorts. Based on radiomics features, radiomics score (RS) models were developed for predicting KRAS proto-oncogene mutations. Furthermore, a composite model combining mixedRS and epidermal growth factor receptor (EGFR) mutation status was developed.Results: Compared with CT model, the PET/CT radiomics score model exhibited higher AUC for predicting KRAS mutations (0.834 vs. 0.770). By integrating EGFR mutation information into the PET/CT RS model, the AUC, sensitivity, specificity, and accuracy for predicting KRAS mutations were all elevated in the validation cohort (0.921, 0.949, 0.872, 0.910 vs. 0.834, 0.923, 0.641, 0.782). By adding EGFR exclusive mutation information, the composite model corrected 64.3% false positive cases produced by the PET/CT RS model in the validation cohort.Conclusion: Integrating EGFR mutation status has potential utility for the optimization of radiomics models for prediction of KRAS gene mutations. This method may be used when repeated biopsies would carry unacceptable risks for the patient.

Part of the patients with incisional hernia (IH) suffered from constipation or even circulatory impairment, which is called large IH with loss of domain (LOD) or giant IH. For now, there is still controversy about the definition and pathomechanism of the LOD; meanwhile, there is no clear criterion for evaluating and treating patients with LOD. A systematic search of the literature was implemented in PubMed and the Cochrane database by using the keywords “IH, abdominal wall function(AWF), LOD” and got 60 publications finally. First, there is still no unified definition for LOD, but we found that it was translated into a situation that abdominal content can hardly be reduced with AWF deficiency in 2018th Chinese Guidelines. Second, we concluded that poor abdominal wall contraction caused by muscular atrophy or fibrillation after large area aponeurosis released shall be important pathomechanism of LOD. Third, we found that there are different methods for evaluating LOD, while the activity evaluation may be most useful. Finally, component separation technique (CST), bridge repair or utotransplantation have been recommended in many publications for variable condition. The definition of LOD is better to be divided into the functional deficiency and the anatomical defect just like Chinese guidelines. The pathomechanism of LOD was actually based on anatomical destruction of abdominal wall contraction system. The activity evaluation may be the most convenient method mentioned in the publications. CST was strongly recommended to be used in giant hernia, the defect of which can be hardly closed. Patients who have IH with LOD are proposed to receive hernioplasty as early as possible because of the impendency to reconstruct the large defect on the abdominal wall as well as restoration of the AWF. Surgeons may select appropriate CST to repair IH according to the length of the defect.

Background/Aims: To investigate the impact of renal denervation (RDN) on myocardial fibrosis and ventricular arrhythmias (VAs) in rats with ischemic cardiomyopathy. Methods: An ischemic cardiomyopathy model was reproduced with myocardial infarction (MI) in adult Sprague–Dawley male rats. The RDN/Sham-RDN procedure was performed at 2 weeks after MI. Sham-MI and sham-RDN rats served as the control group. At 4 weeks after RDN, programmed electrical stimulation (PES) was used to induce VAs, including ventricular tachycardia and ventricular fibrillation, in all 3 groups (MI+RDN, MI, and control groups). At the end of PES, heart and kidney samples were harvested. Immunofluorescence labeling was used to investigate the distribution of connexin 43 (Cx43) in the infarcted border zone. Masson’s trichrome stain was adopted to determine the degree of cardiac fibrosis. Western blotting was performed to identify the expression of transforming growth factor beta 1 (TGF-β1), α-smooth muscle actin (α-SMA), and Cx43. An enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of B-type natriuretic peptide (BNP) and the amino-terminal pro-peptides of type I and III collagen (PINP and PIIINP, respectively) and the expression level of renal norepinephrine. Results: Compared with the MI group, RDN significantly decreased the inducibility of VAs (MI+RDN 3/8 rats vs. MI 8/9 rats, P < 0.05; control 1/8 rats) with PES, reduced myocardial fibrosis estimated by collagen volume fraction (MI+RDN 31.10 ± 3.97% vs. MI 54.80 ± 16.39%, P < 0.001; control 4.41 ± 0.92% ), suppressed TGF-β1 (P < 0.01) and α-SMA (P < 0.001) levels, and attenuated both PINP (MI+RDN 41.44 ± 10.10 ng/mL vs. MI 95.49 ± 24.83 ng/mL, P < 0.001; control 11.90 ± 4.96 ng/mL) and PIIINP (MI+RDN 82.12 ± 30.79 ng/mL vs. MI 124.60 ± 26.64 ng/mL, P < 0.05; control 64.69 ± 23.84 ng/mL) levels. Moreover, RDN reversed the abnormal myocardial distribution of Cx43 and its reduction by MI damage (P < 0.01). Conclusions: RDN reduced myocardial fibrosis and suppressed VAs in a rat model of ischemic cardiomyopathy.

During the period of April and May 2022, Shanghai implemented city-wide static management measures to control the spread of the Omicron variant. Compared to the lockdown in early 2020, the static management in 2022 occurred during the high-ozone season and lasted for a longer duration. It can be considered as a "large-scale field experiment" to study the response of ambient ozone levels to emission reductions. During this period, we conducted comprehensive observations at Fudan University Jiangwan Campus in the northeast corner of Shanghai. Similar experiments were also conducted during the same period in 2020 and 2021. Despite the significant reduction of approximately 30% in VOCs and around 50% in NO2 due to static management in 2022, the average ozone level increased by nearly 23%. This suggests that the reduction in ozone precursors and other pollutants did not lead to a corresponding decrease in ozone concentrations as expected. Cluster analysis of diurnal patterns of ozone concentration revealed four distinct types of diurnal ozone variations. Cluster 3 and Cluster 4, with high ozone levels, experienced significant increases in their share during static management, ultimately leading to an overall increase in average ozone levels in 2022. According to the Observation-Based Model (OBM) simulation analysis, the average peak concentrations of OH, HO2, and RO2 in 2022 were estimated to be 5.3 × 106, 4.9 × 108, and 2.6 × 108 molecules cm-3, respectively, representing an increase of over 30% compared to the levels in 2020 and 2021. Although HONO photolysis was the main contributor to the primary source of ROx radicals, the radical cycling process remained dominant for the overall production of ROx radicals. Due to a significant decrease in NO2 concentration relative to VOCs, the average VOCs/NO2 ratio increased from 1.6 in 2020 to 3.0 in 2022, which is also reflected in the radical cycling. The ratio of OH radical propagation (OH+VOCs) to termination (OH+NO2) was 2.10, higher than 1.03 in 2020 and 1.60 in 2021, indicating that the different reduction proportions of precursors led to a higher VOCs/NO2 ratio, strengthening the radical cycling. The differential reduction in precursor VOCs and NO2 levels due to static management is the underlying cause for the increase in ozone concentration in Shanghai. [ABSTRACT FROM AUTHOR]

Aiming at the complex working conditions environmental factors such as high noise, low illumination, motion blur and mass gangue mixing in coal mines, which lead to the problems of misdetection, omission and low detection accuracy in gangue recognition, a gangue recognition model based on CFS-YOLO algorithm is proposed. The ConvNeXt V2（Convolutional Neural Network with NeXt Units Version 2）feature extraction module is adopted to replace the two C3（Cross stage partial bottle neck mudule）modules at the end of the backbone network, which effectively mitigates the feature collapse problem as well as maintains the diversity of the features in the network delivery process by adding Masked Autoencoder and Global Response Normalization layers to the ConvNeXt architecture. The Focal-EIOU (Focal and Efficient Intersection Over Union) loss function is adopted to replace the original CIOU (Computer Intersection Over Union) loss function to optimize the sample imbalance problem in the bounding box regression task by means of its Focal-Loss mechanism and adjusting the sample weights, which improves the convergence speed and localization accuracy of the model. The parameter-free attention mechanism （Simple Attention Mechanism, SimAM） is added to the back-end of each C3 module of the backbone network to enhance the model's ability of extracting key features of coal gangue targets with large scale variation or low resolution by virtue of its attention weight adaptive adjustment strategy. The effectiveness and superiority of the proposed CFS-YOLO model is verified by ablation and comparison experiments. The experimental results show that the CFS-YOLO model can effectively improve the detection effect of coal gangue under the complex environment of high noise, low illumination, motion blur and large amount of mixed coal gangue in coal mines. The mean Average Presicion (mAP) of the model reaches 90.2%, which is 3.7% higher than the mean Average Presicion (mAP) of the original YOLOv5s model, and the average detection speed reaches 90.09 FPS (Frames Per Second), which can fully satisfy the demand of real-time detection of coal gangue. Meanwhile, compared with six YOLO algorithms such as YOLOv5s, YOLOv7-tiny and YOLOv8n, the CFS-YOLO model has the strongest adaptability to the complex environment of coal mines and the best comprehensive detection performance, which can provide technical support for intelligent and efficient sorting of coal gangue.

BackgroundOxidative Balance Score (OBS) is a novel indicator of the overall antioxidant/oxidant balance, providing a comprehensive reflection of the body’s overall oxidative stress status, with higher OBS suggesting more substantial antioxidant exposures. We aimed to investigate the possible relationship between OBS with serum uric acid (SUA) and hyperuricemia.MethodsData utilized in this study were sourced from the 2011–2018 National Health and Nutrition Examination Survey (NHANES). Participants under 18 years old, those with ≤16 complete data out of 20 OBS components, incomplete serum uric acid data, and missing covariates were excluded from the analysis. OBS was computed by evaluating 16 nutrients and 4 lifestyle factors, encompassing 5 pro-oxidants and 15 antioxidants, guided by a priori knowledge of their relationship with oxidative stress.ResultsA total of 1,5096 individuals were included in our analysis with 49.7% being male, and an average age of 49.05 ± 17.56 years. The mean OBS was 19.76 ± 7.17. Hyperuricemia was present in 19.28% of participants. Due to the right-skewed distribution of the OBS, a natural log transformation was applied to address this issue, and Quartiles of lnOBS 1, 2, 3, and 4 were 1.10–2.56 (N=3526), 2.64–2.94 (N=3748), 3.00–3.22 (N=4026), and 3.26–3.61 (N=3796), respectively. Multivariable logistic regression showed that higher lnOBS quantiles were correlated with lower serum uric acid levels. Compared with the lowest lnOBS quantile, participants in the highest lnOBS quantile had a significant serum uric acid decrease of 16.94 μmol/L for each unit increase in lnOBS (β=-16.94, 95% CI: -20.44, -13.45). Similar negative associations were observed in the second-highest (β=-8.07, 95% CI: -11.45, -4.69) and third-highest (β=-11.69, 95% CI: -15.05, -8.34) lnOBS quantiles. The adjusted odds ratios (ORs) for hyperuricemia in Quartiles 1, 2, 3, and 4 were 1.00, 0.84 (95% CI: 0.75, 0.95), 0.78 (95% CI: 0.69, 0.88), and 0.62 (95% CI: 0.55, 0.71), respectively. Compared to Quartile 1, participants in Quartile 4 had a 38% lower prevalence of hyperuricemia. Subgroup analysis and interaction test showed that there was a significant dependence of sex between OBS and serum uric acid (p for interaction 0.05). Subgroup analysis stratified by age, BMI, hypertension, diabetes, and hyperlipidemia showed there is no significant dependence on these negative correlations (all p for interaction >0.05).ConclusionsThe serum uric acid levels and prevalence of hyperuricemia in US adults exhibited a negative association with OBS. By exploring this connection, our research aims to gain a better understanding of how oxidative balance affects the prevalence of hyperuricemia. This could provide valuable insights for developing preventive strategies and interventions for hyperuricemia. Additional large-scale prospective studies are required to explore the role of OBS in hyperuricemia further.

Migrasomes are organelles produced by migrating cells that form on retraction fibers and are released during cell migration. Migrasomes are involved in physiological and pathological processes such as intercellular communication, cell homeostasis maintenance, signal transduction, disease occurrence and development, and cancer metastasis. In addition, methods and techniques for studying migrasomes are constantly evolving. Here, we review the discovery, formation process, regulation, and known functions of migrasomes, summarize the commonly used specific markers of migrasomes, and the methods for observing migrasomes. Meanwhile, this review also discusses the potential applications of migrasomes in physiological processes, disease diagnosis, treatment, and prognosis, and looks forward to their wider application in biomedicine. In addition, the study of migrasomes will also reveal a new perspective on the mechanism of intercellular communication and promote the further development of life science.

North China Plain suffers from the world’s most severe water scarcity and groundwater depletion due to intensive irrigation for agricultural production. It is imperative to reduce irrigation water consumption while safeguarding crop production and food security. This study conducted a quantitative analysis with deficit irrigation strategies for winter wheat using a water-driven AquaCrop model. After model calibration and validation with field experimental data, we analyzed the irrigation water demand, crop yield, and water productivity (WP) of winter wheat under various deficit irrigation scenarios. A set of optimal irrigation schedules were proposed for different climate years, which significantly mitigated irrigation water usage while sustaining high yields and WPs. The results indicated that despite the irrigation water demand of winter wheat under the future climate scenario was slightly higher than that in the historical period, their crop water sensitive periods (reviving, jointing, and flowering) remained the same. Therefore, we recommended adopting the same deficit irrigation schedules for the historical and future periods. In wet years, adopting a 50% deficit irrigation strategy only reduced crop yields by less than 5% compared with full irrigation, but it saved 1000–1100 m3 of water per hectare and contributed a WP higher than 1.88 kg/m3. While in normal and dry years, an optimal 25% deficit irrigation could sustain over 96% of the maximum yield, meanwhile it could save 650–800 m3/ha of water and achieve almost the same WP as full irrigation. These climate-smart irrigation strategies adapting to diverse climatic conditions largely mitigate agricultural water consumption while maximizing crop productivity and water use efficiency, which are essential for achieving precision irrigation and sustainable water management under a changing climate.

Background: Rab3a regulates vesicle secretion and transport. Emerging evidences have shown that extracellular vesicles (EVs) can reach target lesions of injured spinal cords and exert a positive effect on these lesions. However, the molecular mechanism by which Rab3a regulates vesicle secretion to ameliorate spinal cord injury (SCI) is not fully understood. Methods: An SCI rat model was established which was used to examine the pathological changes and Rab3a expression in spinal cord tissue. Rab3a was overexpressed in the model rats to demonstrate its effect on SCI repair. Rab3a was also knocked down in neuronal cells to verify its role in vesicle secretion and neuronal cells. The binding protein of Rab3a was identified by Co-IP and mass spectrometry. Results: Rab3a was significantly downregulated in SCI rats and Rab3a overexpression promoted SCI repair. Rab3a knockdown inhibited the secretion of neuronal cell-derived EVs. Compared to the EVs from the equal number of control neuronal cells, EVs from Rab3a-knockdown neuronal cells promoted M1 macrophage polarization, which in turn, promoted neuronal cell apoptosis. Mechanistically, STXBP1 was identified as a binding protein of Rab3a, and their interaction promoted the secretion of neuronal cell-derived EVs. Furthermore, METTL2b was significantly downregulated in SCI rats, and METTL2b knockdown significantly reduced Rab3a protein expression. Conclusion: These results suggest that Rab3a promotes the secretion of neuronal cell-derived EVs by interacting with its binding protein STXBP1. Neuronal cells-derived EVs inhibited the polarization of M1 macrophages in the spinal cord microenvironment, thereby promoting SCI repair. Our findings provide a theoretical basis for the clinical treatment of SCI.

ABSTRACT: The present study investigated the effects of replacing part of the basal diet with 2-stage fermented feed (FF) (soybean hulls:rapeseed cake (2:1, m/m)) on the growth performance, immunity, antioxidant capacity, and intestinal health of Chahua chicken. A total of 160 Chahua chickens were randomly divided into 4 groups to receive a control diet or diet with 5%, 10%, or 15% of the basal diet replaced by FF, respectively for 56 d. The results showed that FF significantly improved the average daily gain (ADG) and average daily feed intake (ADFI) of Chahua chickens (P < 0.05). Furthermore, the serum immunoglobulin (Ig) A, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) in Chahua chicken receiving the diet added with 15% FF significantly increased (P < 0.05). Chahua chicken in both the 10% and 15% groups showed increased serum IgG and IgM and decreased malondialdehyde. Serum interleukin-2 and interferon-gamma significantly increased in all FF groups. Compared with the CON group, higher ileal villus height (VH) was found in the 10% FF group. Treatment with FF significantly increased the ileal villus height/crypt depth (VH/CD) ratio, jejunal VH, and jejunal VH/CD ratio while reducing ileal and jejunal CD. The modified gut microbiota composition was observed in the Chahua chicken fed a diet containing FF, in particular, with the increased abundance of Faecalibacterium and Lactobacillus. The abundance of Lactobacillus significantly increased in the 10% and 15% FF groups (all P < 0.05). Correlation analysis revealed a positive correlation between Lactobacillus and VH (R = 0.38, P = 0.10, Figure 3B), AH/CD ratio (R = 0.63, P = 0.003), and a negative correlation with CD (R = −0.72, P = 0.001). These results indicate that FF improves immunity, antioxidant capacity, and intestinal health and consequently enhances growth performance in Chahua chicken.

The external bonding (EB) of fiber-reinforced polymer (FRP) is a usual flexural reinforcement method. When using the technique, premature debonding failure still remains a factor of concern. The effect of incorporating multi-wall carbon nanotubes (MWCNTs) in epoxy resin on the flexural behavior of reinforced concrete (RC) beams strengthened with basalt fiber-reinforced polymer (BFRP) sheets was investigated through four-point bending beam tests. Experimental results indicated that the flexural behavior was significantly improved by the MWCNT-modified epoxy. The BFRP sheets bonded by the MWCNT-modified epoxy more effectively mitigated the debonding failure of BFRP sheets and constrained crack development as well as enhanced the ductility and flexural stiffness of strengthened beams. When the beam was reinforced with two-layer BFRP sheets, the yielding load, ultimate load, ultimate deflection, post-yielded flexural stiffness, energy absorption capacity and deflection ductility of beams strengthened using MWCNT-modified epoxy increased by 7.4%, 8.3%, 18.2%, 22.6%, 29.1% and 14.3%, respectively, in comparison to the beam strengthened using pure epoxy. It could be seen in scanning electron microscopy (SEM) images that the MWCNTs could penetrate into concrete and their pull-out and crack bridging consumed more energy, which remarkably enhanced the flexural behavior of the strengthened beams. Finally, an analytical model was proposed for calculating characteristic loads and characteristic deflections of RC beams strengthened with FRP sheets, which indicated a reasonably good correlation with the experimental results.

Renal hypouricemia (RHUC) is a rare autosomal recessive disorder characterized by impaired renal tubular uric acid reabsorption and abnormally high uric acid clearance, which may be manifested by reduced serum uric acid (SUA) levels and elevated fractional excretion of uric acid (FE-UA >10%). Most RHUC patients are often asymptomatic or have accidentally decreased SUA levels during health examinations, while others develop kidney stones and exercise-induced acute kidney injury (EIAKI). We now report a case of RHUC complicated with an asymptomatic kidney stone, and we identified a heterozygous mutation of c.269G > A (p.R90H) and a novel heterozygous mutation of c.674C > G (p.T225R) in the SLC22A12 gene in the patient through whole exon gene detection (NGS method). This case offers valuable insights into the mechanisms, clinical management, and prognosis of RHUC and its associated complications.