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Abstract Wheat is a crucial crop worldwide, and accurate detection and counting of wheat spikes are vital for yield estimation and breeding. However, these tasks are daunting in complex field environments. To tackle this, we introduce RIA-SpikeNet, a model designed to detect and count wheat spikes in such conditions. First, we introduce an Implicit Decoupling Detection Head to incorporate more implicit knowledge, enabling the model to better distinguish visually similar wheat spikes. Second, Asymmetric Loss is employed as the confidence loss function, enhancing the learning weights of positive and hard samples, thus improving performance in complex scenes. Lastly, the backbone network is modified through reparameterization and the use of larger convolutional kernels, expanding the effective receptive field and improving shape information extraction. These enhancements significantly improve the model’s ability to detect and count wheat spikes accurately. RIA-SpikeNet outperforms the state-of-the-art YOLOv8 detection model, achieving a competitive 81.54% mAP and 90.29% R2. The model demonstrates superior performance in challenging scenarios, providing an effective tool for wheat spike yield estimation in field environments and valuable support for wheat production and breeding efforts.

Abstract Objective To evaluate early bone marrow microvascular changes in alloxan-induced diabetic rabbits using IDEAL-IQ fat quantification, texture analysis based on DCE-MRI Ktrans map, and metabolomics. Materials and methods 24 male Japanese rabbits were randomly divided into diabetic (n = 12) and control (n = 12) groups. All rabbits underwent sagittal MRI of the lumbar vertebrae at the 0th,4th, 8th, 12th, and 16th week, respectively. The fat fraction (FF) ratio and quantitative permeability of the lumbar bone marrow was measured. Texture parameters were extracted from DCE-MRI Ktrans map. At 16th week, lumbar vertebrae 5 and 6 were used for histological analysis. Lumbar vertebra 7 was crushed to obtain bone marrow for metabolomics research. Results The FF ratio and Ktrans of the lumbar bone marrow in diabetic group were increased significantly at 16th week (t = 2.226, P = 0.02; Z = -2.721, P

Abstract Background Patients with non‐small cell lung cancer (NSCLC) with liver metastasis have a poor prognosis, and there are no reliable biomarkers for predicting disease progression. Currently, no recognized and reliable prediction model exists to anticipate liver metastasis in NSCLC, nor have the risk factors influencing its onset time been thoroughly explored. Methods This study conducted a retrospective analysis of 434 NSCLC patients from two hospitals to assess the association between the risk and timing of liver metastasis, as well as several variables. Results The patients were divided into two groups: those without liver metastasis and those with liver metastasis. We constructed a nomogram model for predicting liver metastasis in NSCLC, incorporating elements such as T stage, N stage, M stage, lack of past radical lung cancer surgery, and programmed death ligand 1 (PD‐L1) levels. Furthermore, NSCLC patients with wild‐type EGFR, no prior therapy with tyrosine kinase inhibitors (TKIs), and no prior radical lung cancer surgery showed an elevated risk of early liver metastasis. Conclusion In conclusion, the nomogram model developed in this study has the potential to become a simple, intuitive, and customizable clinical tool for assessing the risk of liver metastasis in NSCLC patients following validation. Furthermore, it provides a framework for investigating the timing of metachronous liver metastasis.

In order to solve the problem of respirable dust pollution in the heading face, a multi-layer spiral spray dust removal method was proposed, in which supersonic pneumatic nozzles were arranged in a spiral shape. Taking the heading face of Qipan Coal Mine as the research object, the three-dimensional numerical model of multi-layer spiral spray dust removal technology device was established by using discrete element and finite element method and k-ω turbulence model and fluid flow particle tracking model in COMSOL software. The velocity field of multi-layer spiral spray air flow, velocity section and trajectory of water mist particles were obtained. The simulation results show that the airflow velocity at the cutting head of the TBM is faster, the farther away from the cutting head, the smaller the airflow velocity, and the airflow near the cutting head is very disorganized; after the nozzle is opened, the water mist particles will form a multi-layer spiral fog curtain, and the spiral fog curtain will cover the entire simulated driving surface after 20 s, and the particle size of the water mist particles is smaller than that of the traditional spray method.

Abstract Low-frequency repetitive transcranial magnetic stimulation (rTMS) has emerged as an effective intervention for alleviating symptoms of psychiatric disorders, particularly schizophrenia characterized by persistent auditory verbal hallucinations (AVH). However, the underlying mechanism of its action remain elusive. This study employed a randomized controlled design to investigate the impact of low-frequency rTMS on the neural connectivity at the stimulate site, specifically left temporoparietal junction (TPJ), in schizophrenia patients with suffering from AVH. Using Dynamic Causal Modeling (DCM), this study assessed changes in directed connectivity patterns and their correlations with clinical symptomatology. The results demonstrated significant improvements in AVH. Notably, significant changes in connectivity were observed, including both abnormal functional connectivity and effective connectivity among multiple brain regions. Particularly, the inhibition effects from the left precentral gyrus and left medial superior frontal gyrus to the left TPJ were closely associated with improvements in AVH. These findings underscore the potential of rTMS to effectively modulate neural pathways implicated in hallucinations in schizophrenia, thereby providing a neurobiological foundation for its therapeutic effects.

Abstract Background Dietary diversity has been suggested as a potential preventive measure against frailty in older adults, but the effect of changes in dietary diversity on frailty is unclear. This study was conducted to examine the association between the dietary diversity score (DDS) and frailty among older Chinese adults. Methods A total of 12,457 adults aged 65 years or older were enrolled from three consecutive and nonoverlapping cohorts from the Chinese Longitudinal Healthy Longevity Survey (the 2002 cohort, the 2005 cohort, and the 2008 cohort). DDS was calculated based on nine predefined food groups, and DDS changes were assessed by comparing scores at baseline and the first follow-up survey. We used 39 self-reported health items to assess frailty. Cox proportional hazard models were performed to examine the association between DDS change patterns and frailty. Results Participants with low-to-low DDS had the highest frailty incidence (111.1/1000 person-years), while high-to-high DDS had the lowest (41.1/1000 person-years). Compared to the high-to-high group of overall DDS pattern, participants in other DDS change patterns had a higher risk of frailty (HRs ranged from 1.25 to 2.15). Similar associations were observed for plant-based and animal-based DDS. Compared to stable DDS changes, participants with an extreme decline in DDS had an increased risk of frailty, with HRs of 1.38 (1.24, 1.53), 1.31 (1.19, 1.44), and 1.29 (1.16, 1.43) for overall, plant-based, and animal-based DDS, respectively. Conclusions Maintaining a lower DDS or having a large reduction in DDS was associated with a higher risk of frailty among Chinese older adults. These findings highlight the importance of improving a diverse diet across old age for preventing frailty in later life.

Rheumatoid arthritis (RA) is an inflammatory disease accompanied by abnormal synovial microenvironment (SM). Sesquiterpene lactones (SLs) are the main anti-inflammatory ingredients of many traditional herbs utilized in RA treatment. α-Methylene-γ-butyrolactone (α-M-γ-B) is a core moiety that widely exists in natural SLs. This study was designed to investigate the anti-arthritic potential of α-M-γ-B as an independent small molecule in vitro and in vivo. α-M-γ-B exhibited stronger electrophilicity and anti-inflammatory effects than the other six analogs. α-M-γ-B inhibited the production of pro-inflammatory mediators via repolarizing M1 macrophages into M2 macrophages. The transcriptome sequencing suggested that α-M-γ-B regulated the immune system pathway. Consistently, α-M-γ-B attenuated collagen type II-induced arthritic (CIA) phenotype, restored the balance of Tregs-macrophages and remodeled SM via repolarizing the synovial-associated macrophages in CIA mice. Mechanistically, although α-M-γ-B did not prevent the trans-nucleus of NF-κB it interfered with the DNA binding activity of NF-κB via direct interaction with the sulfhydryl in cysteine residue of NF-κB p65, which blocked the activation of NF-κB. Inhibition of NF-κB reduced the M1 polarization of macrophage and suppressed the synovial hyperplasia and angiogenesis. α-M-γ-B failed to ameliorate CIA in the presence of N-acetylcysteine or when the mice were subjected to the macrophage-specific deficiency of Rela. In conclusion, α-M-γ-B significantly attenuated the CIA phenotype by directly targeting NF-κB p65 and inhibiting its DNA binding ability. These results suggest that α-M-γ-B has the potential to serve as an alternative candidate for treating RA. The greater electrophilicity of α-M-γ-B, the basis for triggering strong anti-inflammatory activity, accounts for the reason why α-M-γ-B is evolutionarily conserved in the SLs by medical plants.

Abstract Sleep disturbances, including rapid eye movement sleep behavior disorder (RBD), excessive daytime sleepiness, and insomnia, are common non-motor manifestations of Parkinson’s disease (PD). Little is known about the underlying mechanisms, partly due to the inability of current rodent models to adequately mimic the human PD sleep phenotype. Clinically, increasing studies have reported that variants of the glucocerebrosidase gene (GBA) increase the risk of PD. Here, we developed a mouse model characterized by sleep–wakefulness by injecting α-synuclein preformed fibronectin (PFF) into the sublaterodorsal tegmental nucleus (SLD) of GBA L444P mutant mice and investigated the role of the GBA L444P variant in the transition from rapid eye movement sleep behavior disorder to PD. Initially, we analyzed spectral correlates of REM and NREM sleep in GBA L444P mutant mice. Importantly, EEG power spectral analysis revealed that GBA L444P mutation mice exhibited reduced delta power during non-rapid eye movement (NREM) sleep and increased theta power (8.2–10 Hz) in active rapid eye movement (REM) sleep phases. Our study revealed that GBA L444P-mutant mice, after receiving PFF injections, exhibited increased sleep fragmentation, significant motor and cognitive dysfunctions, and loss of dopaminergic neurons in the substantia nigra. Furthermore, the over-expression of GBA-AAV partially improved these sleep disturbances and motor and cognitive impairments. In conclusion, we present the initial evidence that the GBA L444P mutant mouse serves as an essential tool in understanding the complex sleep disturbances associated with PD. This model further provides insights into potential therapeutic approaches, particularly concerning α-synuclein accumulation and its subsequent pathological consequences.

In the process of coal mining, a large amount of respirable dust is generated, which seriously endangers the miners’ health. As the most widely used dust reduction technology, the spray technology has the advantages of high efficiency and cleanliness, but the existing spray technology does not have a strong ability to capture respirable dust, and the atomization efficiency is low. In order to solve those problems, the supersonic coaxial aerodynamic atomization technology was developed. The atomization characteristics of the technology were studied by experimental and numerical simulations, and the dust reduction characteristics of supersonic water drawing siphon aerodynamic atomization and supersonic coaxial atomization were compared based on the self-designed dust reduction experimental platform. At the same time, the dust separation experiment of the two technologies revealed the sedimentation mechanism of dust under the action of supersonic dynamic micro-fog curtain. The results show that under different aerodynamic pressures, the coaxial probe water injection method adopted by the supersonic coaxial atomization dust reduction device greatly reduces the energy loss of the probe structure on the supersonic flow field, significantly improves the atomization efficiency, and produces a large number of high-speed droplets below 11 μm with an uniform spatial distribution, and the particle size is reduced by 12%−50% compared with the siphon atomization device, forming a large-scale high-speed fine fog area in the spray flow field. The coupling effect of the droplet field and the dust field can be characterized by the instantaneous dispersion of the dust and determined by the distribution characteristics of the droplet field. At different times, the variation trend of the graded dust reduction efficiency in each particle size interval is different, and the contribution to the total dust reduction efficiency under different pressures is also different. The large-scale high-speed fine mist generated by the supersonic coaxial atomization technology is easy to capture respirable dust, and the classification efficiency of PM0−PM2.5 is more than 75%, and the maximum is 90%. The increase of pressure enlarges the range of high-speed fine mist, which is conducive to the capture of fine particles. During the confined space migration of dust-containing airflow, the sedimentation process of dust under the action of supersonic dynamic micro-fog curtain can be divided into droplet dust capture area, condensation and sedimentation area, and evaporation escape area. The different behaviors and concentration distributions of fog droplets and dust in different regions are the results of the drag migration of spray airflow and airborne wind flow, the capture of high-speed micro-fog collision, the condensation and settlement of fog droplets, and the weight loss of fog droplet evaporation.

Abstract Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-β1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-β1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.

AIM: To observe the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) secretions on the relevant factors in mouse retinal astrocytes, and to investigate the effect of hUCMSCs on the expression of vascular endothelial growth factor-A (VEGF-A) and to observe the therapeutic effect on the mouse model of retinopathy of prematurity (ROP). METHODS: Cultured hUCMSCs and extracted exosomes from them and then retinal astrocytes were divided into control group and hypoxia group. MTT assay, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect related indicators. Possible mechanisms by which hUCMSCs exosomes affect VEGF-A expression in hypoxia-induced mouse retinal astrocytes were explored. At last, the efficacy of exosomes of UCMSCs in a mouse ROP model was explored. Graphpad6 was used to comprehensively process data information. RESULTS: The secretion was successfully extracted from the culture supernatant of hUCMSCs by gradient ultracentrifugation. Reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α) of mice retinal astrocytes under different hypoxia time and the expression level of VEGF-A protein and VEGF-A mRNA increased, and the ROP cell model was established after 6h of hypoxia. The secretions of medium and high concentrations of hUCMSCs can reduce ROS and HIF-1α, the expression levels of VEGF-A protein and VEGF-A mRNA are statistically significant and concentration dependent. Compared with the ROP cell model group, the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signal pathway related factors in the hUCMSCs exocrine group is significantly decreased. The intravitreal injection of the secretions of medium and high concentrations of hUCMSCs can reduce VEGF-A and HIF-1α in ROP model tissues. HE staining shows that the number of retinal neovascularization in ROP mice decreases with the increase of the dose of hUCMSCs secretion. CONCLUSION: In a hypoxia induced mouse retinal astrocyte model, hUCMSCs exosomes are found to effectively reduce the expression of HIF-1α and VEGF-A, which are positively correlated with the concentration of hUCMSCs exosomes. HUCMSCs exosomes can effectively reduce the number of retinal neovascularization and the expression of HIF-1α and VEGF-A proteins in ROP mice, and are positively correlated with drug dosage. Besides, they can reduce the related factors on the PI3K/AKT/mTOR signaling pathway.

It is known that load forecasting plays an important role for the smart grids and mostly, the users have the combinational load forecast demands with different time-scales. However, due to various internal or external factors, such as poor management, the available load data set is limited. Therefore, the problem becomes as the high-precision combinational load forecast at different time-scales but with limited valid datasets. In this paper, taking the work in a city power company of China as an example, an empirical study for this problem is considered and then a robust forecasting system is built. The forecasting models are designed and screened and then constructed a model library for the system. In order to improve the robustness of the designed system, a mean absolute percentage error (MAPE) based dynamic model selection method is proposed and finally the performance of the system is verified on the State Grid Chongqing Company of China. The results indicate that our designed multi-temporal-spatial-scales load forecast system can dynamically select the best model for different demands, which demonstrates that the build system is an effective and reliable system-level solution. In particular, for the annual based load forecast, 80% of the industries in the considered city have a MAPE less than 5%, while the MAPE of the whole city is less than 2.160%; for the monthly based load forecast, 87% of the industries in the considered city have a MAPE less than 10%, while the MAPE for the whole city is less than 3.755%. In addition, for the annual based forecast, GM(1,1) is mostly used for the industry-based forecasts, but the model with the highest average forecast accuracy is LR-ER. While for region-based forecasts, the mostly selected models are GM(1,n) and AR. For the monthly based forecast, GM(1,1)-SI and FOA-HW have a higher average accuracy than other models for both industries- and region-based forecasts, respectively.

Species with narrow ranges, particularly rare and endangered ones, are more vulnerable to rapid climate change. The endangered Pinaceae species Picea smithiana (Wall.) Boiss. (P. smithiana), endemic to the Himalayan region, is of significant economic and ecological importance. Understanding how its distribution responds to climate change is crucial for effective biodiversity conservation. Our research integrates three species distribution models, i.e. MaxEnt, Random Forest, and Support Vector Machine, to predict the suitable habitat of P. smithiana in the past, present, and future, and to analyze changes in their spatial distribution patterns. Our study also interprets its geographical distribution patterns through an analysis of multiple environmental factors within its suitable habitat. Our results indicate that, since the last glacial maximum, the suitable habitat of P. smithiana has been shifting towards high latitudes and altitudes, corresponding with its cold tolerance traits. Besides the Himalayan region, suitable habitat of P. smithiana were also predicted in Southwest China, despite a lack of observed occurrences, suggesting possible speciation events linked to the uplift of the Qinghai−Tibetan Plateau. Our study warns that the actual distribution of P. smithiana might be more pessimistic than predictions indicate, with protected areas encompassing less than 27 % of its suitable habitat. This highlights the critical need for intensified conservation and management measures to secure the long-term persistence of P. smithiana.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by impairments in social interaction, communication, and repetitive behaviors. Emerging evidence suggests that the insulin-like growth factor (IGF) signaling pathway plays a critical role in ASD pathogenesis; however, the precise pathogenic mechanisms remain elusive. This study utilizes multi-omics approaches to investigate the pathogenic mechanisms of ASD susceptibility genes within the IGF pathway. Whole-exome sequencing (WES) revealed a significant enrichment of rare variants in key IGF signaling components, particularly the IGF receptor 1 (IGF1R), in a cohort of Chinese Han individuals diagnosed with ASD, as well as in ASD patients from the SFARI SPARK WES database. Subsequent single-cell RNA sequencing (scRNA-seq) of cortical tissues from children with ASD demonstrated elevated expression of IGF receptors in parvalbumin (PV) interneurons, suggesting a substantial impact on their development. Notably, IGF1R appears to mediate the effects of IGF2R on these neurons. Additionally, transcriptomic analysis of brain organoids derived from ASD patients indicated a significant association between IGF1R and ASD. Protein-protein interaction (PPI) and gene regulatory network (GRN) analyses further identified ASD susceptibility genes that interact with and regulate IGF1R expression. In conclusion, IGF1R emerges as a central node within the IGF signaling pathway, representing a potential common pathogenic mechanism and therapeutic target for ASD. These findings highlight the need for further investigation into the modulation of this pathway as a strategy for ASD intervention.

BackgroundChemotherapy (CT) remains the primary treatment for locally advanced unresectable pancreatic cancer (LAUPC) and metastatic pancreatic cancer (MPC). The role of radiotherapy (RT) in these conditions remains unclear. This study compares the outcomes of CT alone versus CT combined with RT (combined-modality therapy [CMT]) in LAUPC and MPC patients.Materials and methodsWe conducted a retrospective analysis of LAUPC and MPC patients treated with either CT or CMT from a single institution and Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier curves and Cox hazards models evaluated the association between treatment modalities and overall survival (OS). Propensity score matching (PSM) ensured balanced comparisons. Landmark analysis addressed immortal time bias. Subgroup analyses were based on clinical characteristics. eXtreme Gradient Boosting (XGBoost) and Shapley Additive Explanations (SHAP) assessed outcome prediction and influence of significant predictors.ResultsThe study included 102 patients receiving CMT and 155 receiving CT at single institution, along with 1733 CMT and 9310 CT patients from the SEER dataset. In the single-institution cohort, CMT showed superior survival compared to CT both before (median OS: 20.5 vs. 11.5 months, hazard ratio [HR]: 0.47, 95% CI: 0.34-0.65, P=0.001) and after PSM (median OS: 22.2 vs. 11.8 months, HR: 0.49, 95% CI: 0.30-0.79, P=0.003). Multivariate analyses confirmed that CMT was independently associated with improved OS both before (HR: 0.54, 95% CI: 0.38-0.77, P=0.001) and after PSM (HR: 0.45, 95% CI: 0.27-0.73, P=0.001). Landmark analysis indicated better OS for patients receiving CMT compared to CT alone. Subgroup analysis revealed an OS benefit for CMT across most subgroups. SHAP value analysis indicated that CMT was the most significant contributor to survival outcomes. SEER database validation confirmed these findings.ConclusionsThis study demonstrates that CMT significantly improves OS in LAUPC and MPC patients compared to CT alone. Integrating RT with CT could be beneficial for treating LAUPC and MPC.

Working memory (WM) is an essential cognitive function that underpins various higher-order cognitive processes. Improving WM capacity through targeted training interventions has emergered as a potential approach for enhancing cognitive abilities. The present study employed an 8-week regimen of computerized WM training (WMT) to investigate its effect on neuroplasticity in healthy individuals, utilizing neuroimaging data gathered both before and after the training. The key metrics assessed included the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and the spatial distribution correlations of neurotransmitter. The results indicated that post-training, compared to baseline, there was a reduction in ALFF in the medial superior frontal gyrus and an elevation in ALFF in the left middle occipital gyrus within the training group. In comparison to the control group, the training group also exhibited decreased ALFF in the anterior cingulate cortex, angular gyrus, and superior parietal lobule, along with increased ALFF in the postcentral gyrus post-training. VBM analysis revealed a significant increase in gray matter volume (GMV) in the right dorsal superior frontal gyrus after the training period, compared to the initial baseline measurement. Furthermore, the training group showed GMV increases in the dorsal superior frontal gyrus, Rolandic operculum, precentral gyrus, and postcentral gyrus when compared to the control group. In addition, significant associations were identifed between neuroimaging measurements (AFLL and VBM) and the spatial patterns of neurotransmitters such as serotonin (5-HT), dopamine (DA), and N-methyl-D-aspartate (NMDA), providing insights into the underlying neurochemical processes. These findings clarify the neuroplastic changes caused by WMT, offering a deeper understanding of brain plasticity and highlighting the potential advantages of cognitive training interventions.

Summary: Electroporation temporarily enhances cell membrane permeability and promotes the absorption of external molecules. We have developed a device termed the rolling microneedle electrode array (RoMEA) that combines a densely arranged microneedle array of electrodes with rolling structures. Use RoMEA to create uniform skin micropores for efficient, low-damage transfection of nucleic acids over extended areas of the body. We describe in detail the design, fabrication, and assembly of the device and the application of in vivo electroporation of nucleic acids.For complete details on the use and execution of this protocol, please refer to Tongren Yang et al. 1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Utilizing data that encompass municipalities and regions within China at the prefectural level and beyond, spanning the period from 2012 to 2021, this study employed the spatial Durbin model to assess the spatial spillover impact of the digital economy in propelling low-carbon advancement within regional physical industries. This investigation elucidates the spatial spillover mechanism that underlies the low-carbon evolution of regional industries catalyzed by the digital economy and offers nuanced insights. The findings delineate the following observations: (1) The digital economy propels the low-carbon progression of indigenous physical industries and stimulates the low-carbon development of proximate regions’ physical industries through discernible spatial spillover effects. (2) The spatial spillover ramifications of the digital economy manifest a substantive correlation with urban attributes, including geographical positioning, population size, and market integration levels. Notably, municipalities situated in the southeast coastal region, those characterized by larger population sizes, and those exhibiting heightened market integration levels show greater spatial spillover effects attributable to the digital economy. (3) The safeguarding of intangible asset equity property, a pivotal institutional underpinning for fostering digital economic development, amplifies the spatial spillover effect of the digital economy in propelling low-carbon development within regional industries. (4) As geographical and spatial distances expand, the spatial spillover effect of the digital economy attenuates, indicating a diminishing influence with increasing spatial separation.

Abstract Neural networks are frequently employed to model species distribution through backpropagation methods, known as backpropagation neural networks (BPNN). However, the complex structure of BPNN introduces parameter settings challenges, such as the determination of connection weights, which can affect the accuracy of model simulation. In this paper, we integrated the Grey Wolf Optimizer (GWO) algorithm, renowned for its excellent global search capacity and rapid convergence, to enhance the performance of BPNN. Then we obtained a novel hybrid algorithm, the Grey Wolf Optimizer algorithm optimized backpropagation neural networks algorithm (GNNA), designed for predicting species’ potential distribution. We also compared the GNNA with four prevalent species distribution models (SDMs), namely the generalized boosting model (GBM), generalized linear model (GLM), maximum entropy (MaxEnt), and random forest (RF). These models were evaluated using three evaluation metrics: the area under the receiver operating characteristic curve, Cohen’s kappa, and the true skill statistic, across 23 varied species. Additionally, we examined the predictive accuracy concerning spatial distribution. The results showed that the predictive performance of GNNA was significantly improved compared to BPNN, was significantly better than that of GLM and GBM, and was even comparable to that of MaxEnt and RF in predicting species distributions with small sample sizes. Furthermore, the GNNA demonstrates exceptional powers in forecasting the potential non-native distribution of invasive plant species.

Abstract Background Helicobacter pylori (H. pylori) is the predominant etiological agent of gastritis and disrupts the integrity of the gastric mucosal barrier through various pathogenic mechanisms. After H. pylori invades the gastric mucosa, it interacts with immune cells in the lamina propria. Macrophages are central players in the inflammatory response, and H. pylori stimulates them to secrete a variety of inflammatory factors, leading to the chronic damage of the gastric mucosa. Therefore, the study aims to explore the mechanism of gastric mucosal injury caused by inflammatory factors secreted by macrophages, which may provide a new mechanism for the development of H. pylori-related gastritis. Methods The expression and secretion of CCL3 from H. pylori infected macrophages were detected by RT-qPCR, Western blot and ELISA. The effect of H. pylori-infected macrophage culture medium and CCL3 on gastric epithelial cells tight junctions were analyzed by Western blot, immunofluorescence and transepithelial electrical resistance. EdU and apoptotic flow cytometry assays were used to detect cell proliferation and apoptosis levels. Dual-luciferase reporter assays and chromatin immunoprecipitation assays were used to study CCL3 transcription factors. Finally, gastric mucosal tissue inflammation and CCL3 expression were analyzed by hematoxylin and eosin staining and immunohistochemistry. Results After H. pylori infection, CCL3 expressed and secreted from macrophages were increased. H. pylori-infected macrophage culture medium and CCL3 disrupted gastric epithelial cells tight junctions, while CCL3 neutralizing antibody and receptor inhibitor of CCL3 improved the disruption of tight junctions between cells. In addition, H. pylori-infected macrophage culture medium and CCL3 recombinant proteins stimulated P38 phosphorylation, and P38 phosphorylation inhibitor improved the disruption of tight junctions between cells. Besides, it was identified that STAT1 was a transcription factor of CCL3 and H. pylori stimulated macrophage to secret CCL3 through the JAK1-STAT1 pathway. Finally, after mice were injected with murine CCL3 recombinant protein, the gastric mucosal injury and inflammation were aggravated, and the phosphorylation level of P38 was increased. Conclusions In summary, our findings demonstrate that H. pylori infection stimulates macrophages to secrete CCL3 via the JAK1-STAT1 pathway. Subsequently, CCL3 damages gastric epithelial tight junctions through the phosphorylation of P38. This may be a novel mechanism of gastric mucosal injury in H. pylori-associated gastritis.

To address the issues of shrinkage cracking, high energy consumption and high carbon emission of traditional cement-based sealing materials, the authors investigated the use of sodium alginate (SA) crosslinking metal ions to prepare SA modified alkali activated waste incineration base ash (MSWI-BA) -granulation blast furnace slag (GBFS) based gaging plugging material (SWM). The optimal water-solid ratio was determined by evaluating compressive strength and setting time to be 0.4. The influence of SA modification on the high temperature resistance of the gelling material was investigated by analyzing the compressive strength, shrinkage rate, and fracture morphology of the gelling material at different temperatures. The results showed that after SA modification, the high temperature resistance improved, the surface cracks on the modified cementable material were significantly reduced after heating, and the shrinkage rate was reduced by 26.5% compared to that before modification. The residual compressive strength is still as high as 17.25 MPa after heating at 400 ℃. Combined with microscopic morphology, pore structure properties, and thermal analysis experiments, the generation mechanism of SA modified gelling material was examined. The results revealed that the SA modified MSWI-BA-GBFS based gelling material refines pore size and reduces pore volume via coordination crosslinking of SA and Ca2+/Al3+ and the synergistic effect of the silico-aluminate covalent network, thus maintaining the matrix structure's integrity after heating, improving cracking properties. The simulation findings suggest that the leakage plugging performance of SA modified MSWI-BA-GBFS based gelling material with water solid ratio 0.4 is superior to that of mining cement-based material, demonstrating a better leakage plugging performance. The development of SA modified MSWI-BA-GBFS based gelling plugging material not only provides an effective way for the resource utilization of municipal waste incineration bottom ash, but also provides a type of environmental protection fire-fighting material with high compressive strength, anti-shrinkage cracking, and high temperature resistance, which can completely replace the traditional mine cement based plugging material.

Abstract Background Endoscopic retrograde cholangiopancreatography (ERCP) has found extensive use in pediatric patients; however, challenges persist in the application of therapeutic ERCP in infants. Case presentation This case report details the presentation of a 5.9-kilogram infant with obstructive jaundice and suspected hemolytic anemia who underwent ERCP to alleviate biliary obstruction. The infant was admitted due to clay-colored stools, jaundice, and liver injury. Ultrasound and magnetic resonance cholangiopancreatography (MRCP) revealed dilation of the common bile duct (CBD) accompanied by the presence of stones. ERCP was conducted using a JF-260V duodenoscope under general anesthesia. Successful stone extraction and biliary drainage were achieved. Conclusions In centers with considerable expertise in ERCP and pediatric anesthesia, the use of a conventional adult duodenoscope for therapeutic ERCP in infants can be considered safe and feasible, provided careful and stringent patient selection criteria are applied. In the future, clear guidelines and standardized protocols for the indications and procedures of pediatric ERCP should be established.

Abstract Based on transmission line theory, a 4‐way wideband coupled‐line Wilkinson power divider is designed by the authors, operating from 6 to 18 GHz. It is established by using a novel manufacturing technology with 3D stacked micro‐coaxial line, realising attractive advantages of low insertion (IL) loss and compact size. The simulated result shows that the proposed power divider of 23.5 × 14.46 × 0.9 mm obtains a maximum IL of 0.42 dB over the entire operating band. Measured results are obtained by connecting this micro‐coaxial power divider with printed circuit board, showing that the proposed structure is suitable for microwave communication systems.

Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by Kelch-like ECH-associated protein 1 (Keap1) alkylation plays a central role in anti-inflammatory therapy. However, activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified. Deoxynyboquinone (DNQ) is a natural small molecule discovered from marine actinomycetes. The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1. DNQ exhibited significant anti-inflammatory properties both in vitro and in vivo. The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α, β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine. DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway. Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation. The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry. DNQ triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489 (Cys489) on Keap1-Kelch domain, ultimately enabling the activation of Nrf2. Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α, β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain, suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Highlights A novel aqueous/aprotic electrolyte with low salt concentration (i.e., 0.5 m Zn(CF3SO3)2+1 m LiTFSI) demonstrated an expanded electrochemical window, which can simultaneously stabilize Zn metal anode and increase the operation voltage of Zn-ion hybrid supercapacitors. The coordination shell of the electrolyte induced by acetonitrile and LiTFSI can not only suppress the Zn corrosion and hydrogen evolution reaction but also promote the cathodic stability and ion migration, which is depicted by the density functional theory simulations together with experimental characterizations. The Zn-ion hybrid supercapacitor based on the developed electrolyte can operate within 0–2.2 V in a wide temperature range with an ultra-long lifespan (> 120,000 cycles).

Abstract Background Ropivacaine, a local anesthetic, exhibits anti-tumor effects in various cancer types. However, its specific functions and the molecular mechanisms involved in breast cancer cell stemness remain elusive. Methods The effects of ropivacaine on breast cancer stemness were investigated by in vitro and in vivo assays (i.e., FACs, MTT assay, mammosphere formation assay, transwell assays, western blot, and xenograft model). RNA-seq, bioinformatics analysis, Western blot, Luciferase reporter assay, and CHIP assay were used to explore the mechanistic roles of ropivacaine subsequently. Results Our study showed that ropivacaine remarkably suppressed stem cells-like properties of breast cancer cells both in vitro and in vivo. RNA-seq analysis identified GGT1 as the downstream target gene responding to ropivacaine. High GGT1 levels are positively associated with a poor prognosis in breast cancer. Ropivacaine inhibited GGT1 expression by interacting with the catalytic domain of AKT1 directly to impair its kinase activity with resultant inactivation of NF-κB. Interestingly, NF-κB can bind to the promoter region of GGT1. KEGG and GSEA analysis indicated silence of GGT1 inhibited activation of NF-κB signaling pathway. Depletion of GGT1 diminished stem phenotypes of breast cancer cells, indicating the formation of NF-κB /AKT1/GGT1/NF-κB positive feedback loop in the regulation of ropivacaine-repressed stemness in breast cancer cells. Conclusion Our finding revealed that local anesthetic ropivacaine attenuated breast cancer stemness through AKT1/GGT1/NF-κB signaling pathway, suggesting the potential clinical value of ropivacaine in breast cancer treatment.

Abstract The development of neuromorphic visual systems has recently gained momentum due to their potential in areas such as autonomous vehicles and robotics. However, current machine visual systems based on silicon technology usually contain photosensor arrays, format conversion, memory and processing modules. As a result, the redundant data shuttling between each unit, resulting in large latency and high-power consumption, seriously limits the performance of neuromorphic vision chips. Here, we demonstrate an artificial neural network (ANN) architecture based on an integrated 2D MoS2/Ag nanograting phototransistor array, which can simultaneously sense, pre-process and recognize optical images without latency. The pre-processing function of the device under photoelectric synergy ensures considerable improvement of efficiency and accuracy of subsequent image recognition. The comprehensive performance of the proof-of-concept device demonstrates great potential for machine vision applications in terms of large dynamic range (180 dB), high speed (500 ns) and low energy consumption per spike (2.4 × 10−17 J).

Abstract Background The neural cells in the brains of patients with Parkinson’s disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson’s disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson’s disease based on the central-peripheral-central theory. Methods The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson’s disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. Discussion The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. Trial registration Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023.

Highlights Enhancing rate performance of cellulose-derived hard carbon anodes from the view of cellulose molecular, crystalline, and aggregation structure is explored. Relationship of storage sodium and rate performance according to theoretical calculation and characterization analysis is illustrated. Cellulose intrinsic microstructure, conversion relationship between the allotropes of cellulose, and the critical influences on cellulose-derived carbon structure are discussed.

Rosa roxburghii fruit is rich in flavonoids, but little is known about their biosynthetic pathways. In this study, we employed transcriptomics and metabolomics to study changes related to the flavonoids at five different stages of R. roxburghii fruit development. Flavonoids and the genes related to their biosynthesis were found to undergo significant changes in abundance across different developmental stages, and numerous quercetin derivatives were identified. We found three gene expression modules that were significantly associated with the abundances of the different flavonoids in R. roxburghii and identified three structural UDP-glycosyltransferase genes directly involved in the synthesis of quercetin derivatives within these modules. In addition, we found that RrBEH4, RrLBD1 and RrPIF8 could significantly increase the expression of downstream quercetin derivative biosynthesis genes. Taken together, these results provide new insights into the metabolism of flavonoids and the accumulation of quercetin derivatives in R. roxburghii.