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Abstract Liver ultrasound is widely used in clinical practice due to its advantages of non-invasiveness, non-radiation, and real-time imaging. Accurate segmentation of the liver region in ultrasound images is essential for accelerating the auxiliary diagnosis of liver-related diseases. This paper proposes BACANet, a deep learning algorithm designed for real-time liver ultrasound segmentation. Our approach utilizes a lightweight network backbone for liver feature extraction and incorporates a convolutional attention mechanism to enhance the network's ability to capture global contextual information. To improve early localization of liver boundaries, we developed a selective large kernel convolution module for boundary feature extraction and introduced explicit liver boundary supervision. Additionally, we designed an enhanced attention gate to efficiently convey liver body and boundary features to the decoder to enhance the feature representation capability. Experimental results across multiple datasets demonstrate that BACANet effectively completes the task of liver ultrasound segmentation, achieving a balance between inference speed and segmentation accuracy. On a public dataset, BACANet achieved a DSC of 0.921 and an IOU of 0.854. On a private test dataset, BACANet achieved a DSC of 0.950 and an IOU of 0.907, with an inference time of approximately 0.32 s per image on a CPU processor.

Abstract Background Dentatorubral-pallidoluysian atrophy is a rare autosomal dominant neurodegenerative disease. It is a rare disease in the world. Therefore, sharing clinical encounters of this case can deepen global awareness and understanding of the disease. Case presentation The patient was a 34-year-old male of Han nationality who was unmarried. The patient was admitted owing to weakness of the left lower limb with walking instability for 2 months and aggravation for 1 month. There was no dizziness, headache, numbness of limbs, convulsions, nausea, vomiting, abdominal pain, ataxia, nausea, vomiting, or abdominal pain. No nausea, vomiting, diarrhea, abdominal distension, tinnitus, hearing loss, fever, cough, expectoration. Personal history: worked in Cambodia 5 years ago, worked in Dubai 3 years ago, engaged in computer work, smoking or drinking habits. The patient was unmarried. Family history: the mother had symptoms similar to walking unsteadily (undiagnosed). Positive signs include a wide-base gait with a rotatory nystagmus that jumps upward in both eyes. Bilateral finger-nose instability test was quasi-positive, rapid alternating test was negative, and eye closure tolerance test was positive. Tendon reflexes were active in both upper limbs and hyperreflexia in both lower limbs. Stability of the heel, knee, and tibia. Genetic testing showed that the number of repeats in the dentatorubral-pallidoluysian atrophy ATN1 gene was 18 and 62, and the (CAG)n repeat sequence in the ATN1 gene was abnormal, with a repeat number of 62, and the patient was a pathogenic variant. The patient was diagnosed with dentatorubral-pallidoluysian atrophy. Dentatorubral-pallidoluysian atrophy remains a progressive neurodegenerative disease with no effective treatment. At present, the proband is taking 5 mg of buspirone three times a day, which has been reported to improve the symptoms. The patient was followed up for 6 months after taking buspirone, and there was no significant improvement in the temporary symptoms. At present, there are few cases of dentatorubral-pallidoluysian atrophy, and the characteristics of nystagmus in this disease have not been proposed in the past. This case reported the unusual presentation of nystagmus. Conclusion Dentatorubral-pallidoluygur atrophy is a rare neurodegenerative disease with autosomal dominant inheritance. To the best of our knowledge, our present case report is the first case report of dentatorubral-pallidoluygur atrophy with specific nystagmus. We describe the special eye shake and its positive signs to increase dentatorubral-pallidoluysian atrophy clinical positive signs.

Abstract While circulating metabolites and immune system have been increasingly linked to hypothyroidism risk, the causality underlying these associations remains largely uninterrogated. We used Mendelian randomization to identified putative causal traits for hypothyroidism via integrating omics data. Briefly, we utilized 1180 plasma metabolites and 731 immune cells traits as exposures to identify putatively causal traits for hypothyroidism in the discovery (40,926 cases) and replication cohorts (14,871 cases). By combining MR results from two large-scale cohorts, we ultimately identified 21 putatively causal traits, including five plasma metabolites and 16 immune cell traits. CD3 on CD28+ CD4+ T cell and 1-(1-enyl-palmitoyl)-2-oleoyl-GPE (p-16:0/18:1) demonstrated the most pronounced positive and negative associations with hypothyroidism risk, respectively. The odds ratio and 95% confidence interval were 1.09 (1.07, 1.12) and 0.81 (0.75, 0.87), respectively. No evidence of horizontal pleiotropy, heterogeneity among instrumental variables or reverse causation were found for these 21 significant associations. Our study elucidates key metabolites and immune cell traits associated with hypothyroidism. These findings provide new insights into the etiology and potential therapeutic targets for hypothyroidism.

Abstract Background Jasmonate ZIM-domain (JAZ) proteins, which act as negative regulators in the jasmonic acid (JA) signalling pathway, have significant implications for plant development and response to abiotic stress. Results Through a comprehensive genome-wide analysis, a total of 20 members of the JAZ gene family specific to alfalfa were identified in its genome. Phylogenetic analysis divided these 20 MsJAZ genes into five subgroups. Gene structure analysis, protein motif analysis, and 3D protein structure analysis revealed that alfalfa JAZ genes in the same evolutionary branch share similar exon‒intron, motif, and 3D structure compositions. Eight segmental duplication events were identified among these 20 MsJAZ genes through collinearity analysis. Among the 32 chromosomes of the autotetraploid cultivated alfalfa, there were 20 MsJAZ genes distributed on 17 chromosomes. Extensive stress-related cis-acting elements were detected in the upstream sequences of MsJAZ genes, suggesting that their response to stress has an underlying function. Furthermore, the expression levels of MsJAZ genes were examined across various tissues and under the influence of salt stress conditions, revealing tissue-specific expression and regulation by salt stress. Through RT‒qPCR experiments, it was discovered that the relative expression levels of these six MsJAZ genes increased under salt stress. Conclusions In summary, our study represents the first comprehensive identification and analysis of the JAZ gene family in alfalfa. These results provide important information for exploring the mechanism of JAZ genes in alfalfa salt tolerance and identifying candidate genes for improving the salt tolerance of autotetraploid cultivated alfalfa via genetic engineering in the future.

ABSTRACT: The relationship between saturated fatty acids (SFA) and bladder cancer (BC) risk has been conflicting. Our aim was to investigate the relationship between erythrocyte membrane SFA and BC risk. A total of 404 participants were enrolled in the study (including 112 cases and 292 controls). A validated food frequency questionnaire was used to assess the food intake. The constitutive composition of fatty acids in the erythrocyte membrane was measured by gas chromatography. After adjustment for BC risk factors, SFA had no significant association with BC risk. However, C18:0 was positively linked with BC risk with an odds ratio (OR; 95% CI) of 2.99 (1.37–6.53). In contrast, very-long-chain saturated fatty acids (VLCSFA), especially C24:0, were negatively related to BC risk with an OR (95% CI) of 0.28 (0.12–0.65) for VLCSFA and 0.33 (0.15–0.75) for C24:0. Higher total odd-chain SFA (C15:0 and C17:0) were associated with a lower risk of BC with OR (95% CI) of 0.18 (0.076–0.44), 0.18 (0.068–0.47), 0.34 (0.14–0.81), respectively. After subgroup analysis, the protective effects C15:0 and C17:0 were still remained. Receiver operating characteristic analysis displayed that the combination of C15:0 and C17:0 indexes increased the accurate predictive rate of BC risk. Further mediation effect analysis showed that C15:0 and C17:0 could be used as partial mediation effectors for milk and dairy products and bladder carcinogenesis. Overall, the combination of odd-chain SFA (C15:0 and C17:0) in the erythrocyte membrane could serve as a reliable mediator and predictor, indicating a relationship between a high intake of milk and dairy products and a lower risk of BC.

The importance of determining the radon exhalation rate from water surface is emphasized by the increased use of radon and its daughter products as tracers in large-scale circulation studies of the atmosphere. There were many methods to measure radon exhalation from water surface. With the development of radon exhalation rate measurement methods and instruments on the surface of the soil, the rock and building materials, so the radon exhalation rate from water surface can be more accurately measured by applying these improved methods and instruments. In this paper, a cuboid accumulation chamber surrounded by foam boards and a RAD7 were used to measure the radon exhalation rate on the water surface at three different positions by Yixin lake. Each measurement was performed 2 h. The radon exhalation rate from the water surface was about 6 × 10−3 Bq m−2s−1. The thoron exhalation rate from the water surface also can be estimated, it is about 0.16 Bq m−2s−1. These results hint that the radon transmission from the lake bottom soil to water and then into the atmosphere.

Background and aims: Alcohol-related liver disease (ALD) is a worldwide burden. Cuproptosis has been shown to play a key role in the development of several diseases. However, the role and mechanisms of cuproptosis in ALD remain unclear. Methods: The RNA-sequencing data of ALD liver samples were downloaded from the Gene Expression Omnibus (GEO) database. Bioinformatical analyses were performed using the R data package. We then identified key genes through multiple machine learning methods. Immunoinfiltration analyses were used to identify different immune cells in ALD patients and controls. The expression levels of key genes were further verified. Results: We identified three key cuproptosis-related genes (CRGs) (DPYD, SLC31A1, and DBT) through an in-depth analysis of two GEO datasets, including 28 ALD samples and eight control samples. The area under the curve (AUC) value of these three genes combined in determining ALD was 1.0. In the external datasets, the three key genes had AUC values as high as 1.0 and 0.917, respectively. Nomogram, decision curve, and calibration curve analyses also confirmed these genes’ ability to predict the diagnosis. These three key genes were found to be involved in multiple pathways associated with ALD progression. We confirmed the mRNA expression of these three key genes in mouse ALD liver samples. Regarding immune cell infiltration, the numbers of B cells, CD8 (+) T cells, NK cells, T-helper cells, and Th1 cells were significantly lower in ALD patient samples than in control liver samples. Single sample gene set enrichment analysis (ssGSEA) was then used to estimate the immune microenvironment of different CRG clusters and CRG-related gene clusters. In addition, we calculated CRG scores through principal component analysis (PCA) and selected Sankey plots to represent the correlation between CRG clusters, gene clusters, and CRG scores. Finally, the three key genes were confirmed in mouse ALD liver samples and liver cells treated with ethanol. Conclusions: We first established a prognostic model for ALD based on 3 CRGs and robust prediction efficacy was confirmed. Our investigation contributes to a comprehensive understanding of the role of cuproptosis in ALD, presenting promising avenues for the exploration of therapeutic strategies.

Arsenic, a neurotoxic metalloid, poses significant health risks. However, ellagic acid, renowned for its antioxidant properties, has shown potential in neuroprotection. This study aimed to investigate the neuroprotective effects of ellagic acid against arsenic-induced neuronal ferroptosis and cognitive impairment and elucidate the underlying mechanisms. Using an arsenic-exposed Wistar rat model and an arsenic-induced HT22 cells model, we assessed cognitive ability, measured serum and brain arsenic levels, and evaluated pathological damage through histological analysis and transmission electron microscopy. Additionally, we examined oxidative stress and iron ion levels using GSH, MDA, ROS and tissue iron biochemical kits, and analyzed the expression of ferroptosis-related markers using western blot and qRT-PCR. Our results revealed that arsenic exposure increased both serum and brain arsenic levels, resulting in hippocampal pathological damage and subsequent decline in learning and memory abilities. Arsenic-induced neuronal ferroptosis was mediated by the inhibition of the xCT/GSH/GPX4/Nrf2 signaling axis and disruption of iron metabolism. Notably, ellagic acid intervention effectively reduced serum and brain arsenic levels, ameliorated neuronal damage, and improved oxidative stress, ferroptosis, and cognitive impairment. These beneficial effects were associated with the activation of the Nrf2/Keap1 signaling pathway, upregulation of GPX4 expression, and enhanced iron ion excretion. In conclusion, ellagic acid demonstrates promising neuroprotective effects against arsenic-induced neurotoxicity by mitigating neuronal ferroptosis and cognitive impairment.

A 40-year-old male patient was admitted due to abdominal distension and discomfort in the upper abdomen persisting for three days. Enhanced CT of the upper abdomen revealed an irregularly dense soft tissue area in the body and tail of the pancreas, approximately 7.6 × 3.1 cm in size, with blurred boundaries, and indistinct separation from the splenic artery and vein. Multiple liver lesions of varying sizes and slightly lower densities were also observed. Liver tumor biopsy considering a neuroendocrine tumor G2, combined with the medical history, led to a diagnosis of pancreatic neuroendocrine tumor G2 with liver metastasis. Physical examination showed mild tenderness in the upper abdomen but no other significant positive signs. During treatment, the patient developed multiple red papular rashes around the mouth, on both lower limbs, and the perineum, accompanied by itching. The glucagon level was 1138.3 pg/L. The patient underwent resection of the pancreatic body and tail, splenectomy, partial liver tumor resection, and cholecystectomy. Within five days post-surgery, the skin lesions began to crust and flake off. On the 14th day post-surgery, the serum glucagon level was rechecked at 136.4 pg/L. As of April 2024, progression of liver lesions was noted, with no significant skin symptoms during the period.

In hippocampus, synaptic plasticity and rhythmic oscillations reflect the cytological basis and the intermediate level of cognition, respectively. Transcranial ultrasound stimulation (TUS) has demonstrated the ability to elicit changes in neural response. However, the modulatory effect of TUS on synaptic plasticity and rhythmic oscillations was insufficient in the present studies, which may be attributed to the fact that TUS acts mainly through mechanical forces. To enhance the modulatory effect on synaptic plasticity and rhythmic oscillations, transcranial magneto-acoustic stimulation (TMAS) which induced a coupled electric field together with TUS’s ultrasound field was applied. The modulatory effect of TMAS and TUS with a pulse repetition frequency of 100 Hz were compared. TMAS/TUS were performed on C57 mice for 7 days at two different ultrasound intensities (3 W/cm2 and 5 W/cm $^{{2}}\text {)}$ . Behavioral tests, long-term potential (LTP) and local field potentials in vivo were performed to evaluate TUS/TMAS modulatory effect on cognition, synaptic plasticity and rhythmic oscillations. Protein expression based on western blotting were used to investigate the under- lying mechanisms of these beneficial effects. At 5 W/cm2, TMAS-induced LTP were 113.4% compared to the sham group and 110.5% compared to TUS. Moreover, the relative power of high gamma oscillations (50-100Hz) in the TMAS group ( $1.060\pm 0.155$ %) was markedly higher than that in the TUS group ( $0.560\pm 0.114$ %) and sham group ( $0.570\pm 0.088$ %). TMAS significantly enhanced the synchronization of theta and gamma oscillations as well as theta-gamma cross-frequency coupling. Whereas, TUS did not show relative enhancements. TMAS provides enhanced effect for modulating the synaptic plasticity and rhythmic oscillations in hippocampus.

The recent discovery of large oil and gas fields in the deep-water of the Senegal Basin has drawn global attention. Despite this, several exploration wells in this area fail, which can be primarily contributed to a lack of understanding of the basin's structures and hydrocarbon accumulation conditions. This study examines these characteristics utilizing gravity, seismic and drilling data, and finally makes a comparison with the Cote d’Ivoire Basin, a typical transform margin basin in the South Atlantic. The results suggest that the Senegal Basin, influenced by multiple transform faults and a weak Paleozoic basement, experienced three evolutionary stages: rifting, transitional, and drifting. Each stage contributed to the development of distinct depositional sequences - syn-rift sequences, sag sequences, and continental margin sequences, respectively. The Triassic - Early Jurassic rifting stage predominantly formed continental deposits, like fluvial, lacustrine, and deltaic deposits, in the syn-rift sequences. The Middle-Late Jurassic transitional stage, influenced by transform faults, witnessed the formation of marginal ridges or submarine uplift zones. These zones, in conjunction with landward high terrains, formed a restricted environment promoting the development of source rocks in the sag sequences. During the drifting stage, three types of reservoirs, namely platform carbonate rocks, deltas, and slope-floor fans were formed. Notably, large-scale hydrocarbon reservoirs have been found in the deltas and the slope-floor fans both in the Senegal Basin and the Cote d’Ivoire Basin. The Upper Jurassic - Aptian platforms exhibit thick carbonate rocks and organic reefs on their edges, suggesting substantial potential for hydrocarbon exploration in the Senegal Basin.

For Volterra integro-differential equations (VIDEs) with weakly singular kernels, their solutions are singular at the initial time. This property brings a great challenge to traditional numerical methods. Here, we investigate the numerical approximation for the solution of the nonlinear model with weakly singular kernels. Due to its characteristic, we split the interval and focus on the first one to save operation. We employ the corresponding singular functions as basis functions in the first interval to simulate its singular behavior, and take the Legendre polynomials as basis functions in the other one. Then the corresponding hp-version spectral method is proposed, the existence and uniqueness of solution to the numerical scheme are proved, the hp-version optimal convergence is derived. Numerical experiments verify the effectiveness of the proposed method.

Background and aimsCuproptosis has emerged as a significant contributor in the progression of various diseases. This study aimed to assess the potential impact of cuproptosis-related genes (CRGs) on the development of hepatic ischemia and reperfusion injury (HIRI).MethodsThe datasets related to HIRI were sourced from the Gene Expression Omnibus database. The comparative analysis of differential gene expression involving CRGs was performed between HIRI and normal liver samples. Correlation analysis, function enrichment analyses, and protein-protein interactions were employed to understand the interactions and roles of these genes. Machine learning techniques were used to identify hub genes. Additionally, differences in immune cell infiltration between HIRI patients and controls were analyzed. Quantitative real-time PCR and western blotting were used to verify the expression of the hub genes.ResultsSeventy-five HIRI and 80 control samples from three databases were included in the bioinformatics analysis. Three hub CRGs (NLRP3, ATP7B and NFE2L2) were identified using three machine learning models. Diagnostic accuracy was assessed using a receiver operating characteristic (ROC) curve for the hub genes, which yielded an area under the ROC curve (AUC) of 0.832. Remarkably, in the validation datasets GSE15480 and GSE228782, the three hub genes had AUC reached 0.904. Additional analyses, including nomograms, decision curves, and calibration curves, supported their predictive power for diagnosis. Enrichment analyses indicated the involvement of these genes in multiple pathways associated with HIRI progression. Comparative assessments using CIBERSORT and gene set enrichment analysis suggested elevated expression of these hub genes in activated dendritic cells, neutrophils, activated CD4 memory T cells, and activated mast cells in HIRI samples versus controls. A ceRNA network underscored a complex regulatory interplay among genes. The genes mRNA and protein levels were also verified in HIRI-affected mouse liver tissues.ConclusionOur findings have provided a comprehensive understanding of the association between cuproptosis and HIRI, establishing a promising diagnostic pattern and identifying latent therapeutic targets for HIRI treatment. Additionally, our study offers novel insights to delve deeper into the underlying mechanisms of HIRI.

Study Region: A well-irrigated area along the Yellow River in the North China Plain. Study Focus: High nitrate concentrations in groundwater induced by soil nitrate leaching are found worldwide. In this research, we examined the main processes and mechanisms of nitrate leaching with 16 years of long-term observational data to evaluate the potential threat of nitrate pollution to the groundwater in a well-irrigated area. New Hydrological Insights for the Region: This study uncovered significant differences in the primary mechanisms of nitrate leaching in the region at different stages in response to the continuous groundwater table decline. In the first stage, groundwater tables were less than 5 m, nitrate leaching was mainly driven by irrigation or precipitation with average annual percolation of 116.8 mm. In the second stage, groundwater overexploitation led to a decline in the groundwater table, inducing the internal drainage and nitrate leaching of the lower root zone. In the third stage, a further decline of groundwater table almost cut off the hydrological connection of root zone to the groundwater, which hampered water percolation and thus nitrate leaching from the root zone during next irrigation or precipitation. However, one extreme precipitation as much as in 2021 washed out almost all the accumulated nitrate in the root zone. The findings provide a reference for nitrogen management and groundwater protection in similar regions.

Abstract The production of semen in boars involves multiple reproductive glands, including the testis (Tes), epididymis (Epi), vesicular gland (VG), prostate gland (PG), and bulbourethral gland (BG). However, previous studies on boar reproduction primarily focused on the testis, with little attention paid to the other glands. Here, we integrated single-molecule long-read sequencing with short-read sequencing to characterize the RNA landscape from five glands of Banna mini-pig inbred line (BMI) and Diannan small-ear pigs (DSE). We identified 110,996 full-length isoforms from 22,298 genes, and classified the alternative splicing (AS) events in these five glands. Transcriptome-wide variation analysis indicated that the number of single nucleotide polymorphisms (SNPs) in five tissues of BMI was significantly lower than that in the non-inbred pig, DSE, revealing the effect of inbreeding on BMI. Additionally, we performed small-RNA sequencing and identified 299 novel miRNAs across all glands. Overall, our findings provide a comprehensive overview of the RNA landscape within these five glands, paving the path for future investigations on reproductive biology and the impact of inbreeding on pig transcriptome.

Lipoxygenase (LOX) is associated with responses to plant hormones, environmental stresses, and signaling substances. Methyl jasmonate (MeJA) treatment triggers the production of LOX, polyphenol oxidase, and protease inhibitors in various plants, producing resistance to herbivory. To examine the response of MtLOX24 to MeJA, the phenotypic and physiological changes in Medicago truncatula MtLOX24 overexpression and lox mutant plants were investigated. Additionally, wild-type R108, the MtLOX24-overexpressing line L4, and the mutant lox-1 were utilized as experimental materials to characterize the differentially expressed genes (DEGs) and metabolic pathways in response to MeJA. The results indicate that after treatment with 200 µM of MeJA, the damage in the mutants lox-1 and lox-2 was more serious than in the overexpressing lines L4 and L6, with more significant leaf wilting, yellowing, and oxidative damage in lox-1 and lox-2. Exogenous application of MeJA induced H2O2 production and POD activity but reduced CAT activity in the lox mutants. Transcriptome analysis revealed 10,238 DEGs in six libraries of normal-growing groups (cR108, cL4, and clox1) and MeJA-treated groups (R108, L4, and lox1). GO and KEGG functional enrichment analysis demonstrated that under normal growth conditions, the DEGs between the cL4 vs. cR108 and the clox-1 vs. cR108 groups were primarily enriched in signaling pathways such as plant–pathogen interactions, flavonoid biosynthesis, plant hormone signal transduction, the MAPK signaling pathway, and glutathione metabolism. The DEGs of the R108 vs. cR108 and L4 vs. cL4 groups after MeJA treatment were mainly enriched in glutathione metabolism, phenylpropanoid biosynthesis, the MAPK signaling pathway, circadian rhythm, and α-linolenic acid metabolism. Among them, under normal growth conditions, genes like PTI5, PR1, HSPs, PALs, CAD, CCoAOMT, and CYPs showed significant differences between L4 and the wild type, suggesting that the expression of these genes is impacted by MtLOX24 overexpression. CDPKs, CaMCMLs, IFS, JAZ, and other genes were also significantly different between L4 and the wild type upon MeJA treatment, suggesting that they might be important genes involved in JA signaling. This study provides a reference for the study of the response mechanism of MtLOX24 under MeJA signaling.

Transcranial magneto-acoustic stimulation (TMAS), which is characterized by high spatiotemporal resolution and high penetrability, is a non-invasive neuromodulation technology based on the magnetic–acoustic coupling effect. To reveal the effects of TMAS treatment on amyloid-beta (Aβ) plaque and synaptic plasticity in Alzheimer’s disease, we conducted a comparative analysis of TMAS and transcranial ultrasound stimulation (TUS) based on acoustic effects in 5xFAD mice and BV2 microglia cells. We found that the TMAS-TUS treatment effectively reduced amyloid plaque loads and plaque-associated neurotoxicity. Additionally, TMAS-TUS treatment ameliorated impairments in long-term memory formation and long-term potentiation. Moreover, TMAS-TUS treatment stimulated microglial proliferation and migration while enhancing the phagocytosis and clearance of Aβ. In 5xFAD mice with induced microglial exhaustion, TMAS-TUS treatment-mediated Aβ plaque reduction, synaptic rehabilitation improvement, and the increase in phospho-AKT levels were diminished. Overall, our study highlights that stimulation of hippocampal microglia by TMAS treatment can induce anti-cognitive impairment effects via PI3K-AKT signaling, providing hope for the development of new strategies for an adjuvant therapy for Alzheimer’s disease.

The low hilly area is a major landform in the west of Henan province, China, and it is suffering soil and water loss because of human activities. The silvopastoral system that combines trees and grasses has been widely used to restore this fragile area. We conducted in situ field experiments in 2011 in the low hilly area of Henan province involving pure forests of Populus simonii (PS; Salicaceae), Platycladus orientalis (PO; Cupressaceae), Quercusvariabilis (QV; Fagaceae), and Robinia pseudoacacia (RP; Fabaceae), and also with each forest tree species being combined with Medicago sativa (MS; Fabaceae) as silvopastoral systems, i.e., PS-MS, PO-MS, QV-MS, and RP-MS, respectively. We recorded tree diameter at breast height (DBH) and tree height (TH) in the years 2014–2016, 2018, 2020, and 2022 for all the different vegetation types. Tree biomass load (TBL, i.e., tree biomass per unit area) was estimated based on DBH and TH using allometric equations for each tree species. Generally, the results showed that the DBH, TH, and TBL were promoted in the silvopastoral systems PS-MS, PO-MS, and QV-MS. Specially, the DBH and TBL of PS-MS and PO-MS tended to be higher and were significantly higher than the pure forests of PS and MS, respectively, in 2014–2016; the silvopastoral systems were not significantly different from the pure forests for DBH in 2018 and 2022, and for TBL in 2018 and 2020. TH was lower in PS-MS and PO-MS than that in PS and PO in 2014–2016, while there was no difference of TH between PS-MS and PS in 2018 and 2022, and TH was higher in PO-MS than that in PO in 2018, 2020 and 2022. The DBH, TH, and TBL were all higher in QV-MS than QV. The TBL in RP-MS was non-significant or lower compared to that in RP. Moreover, TBL tended to be lower in upslope positions than downslope in the pure forests, while there was no difference in most silvopastoral systems. In summary, PS and PO may be suggested as the tree species selection in vegetation restoration processes for about five years, QV may be a better alternative for a long term, while RP is not recommended.

Alfalfa is the most widely cultivated perennial legume forage crop worldwide. Drought is one of the major environmental factors influencing alfalfa productivity. However, the molecular mechanisms underlying alfalfa responses to drought stress are still largely unknown. This study identified a drought-inducible gene of unknown function, designated as Medicago sativa DROUGHT-INDUCED UNKNOWN PROTEIN 1 (MsDIUP1). MsDIUP1 was localized to the nucleus, chloroplast, and plasma membranes. Overexpression of MsDIUP1 in Arabidopsis resulted in increased tolerance to drought, with higher seed germination, root length, fresh weight, and survival rate than in wild-type (WT) plants. Consistently, analysis of MsDIUP1 over-expression (OE) alfalfa plants revealed that MsDIUP1 also increased tolerance to drought stress, accompanied by physiological changes including reduced malondialdehyde (MDA) content and increased osmoprotectants accumulation (free proline and soluble sugar), relative to the WT. In contrast, disruption of MsDIUP1 expression by RNA interference (RNAi) in alfalfa resulted in a drought-hypersensitive phenotype, with a lower chlorophyll content, higher MDA content, and less osmoprotectants accumulation than that of the WT. Transcript profiling of alfalfa WT, OE, and RNAi plants during drought stress showed differential responses for genes involved in stress signaling, antioxidant defense, and osmotic adjustment. Taken together, these results reveal a positive role for MsDIUP1 in regulating drought tolerance.

In this paper, a multivariate cooperative internal mode control method based on RBF neural network (RBF-NN) inverse system is proposed to suppress the chaotic behavior in the power system. Firstly, a seven-dimensional model of the controlled power system including energy storage (ES) and static var compensator (SVC) is constructed, and the chaotic dynamics of the system is analyzed by local bifurcation diagram, attractor phase diagram and timing diagram, and the merging crisis and coexistence of chaotic attractors are found in the power system under the action of the low-frequency power disturbance. Secondly, considering the parameter uncertainties of the power system, an RBF-NN inverse system model of the controlled power system is established based on inverse system theory and neural network theory to realize its pseudo-linearization, and a multivariable cooperative internal mode controller is designed to suppress the chaotic behavior in the power system by combining the ES and the SVC. Finally, the effectiveness and robustness of the proposed chaos suppression control strategy are verified by simulation.

Adversarial attacks have threatened the credibility of machine learning models and cast doubts over the integrity of data. The attacks have created much harm in the fields of computer vision, and natural language processing. In this paper, we focus on the adversarial attack, in particular the poisoning attack, against the network intrusion detection system (NIDS), which is often viewed as the first line of defense against cyber threats. We develop a generative adversarial network (GAN) in AIGAN, which uses deep learning techniques to generate adversarial data and to conduct an anomaly attack on IoT networks. To evaluate the effectiveness of our generator, we measure the similarities between real and fake data using the Jaccard similarity index, in addition comparing the F1-scores from four generic algorithms: multilayer perception, logistic regression, decision tree, random forest. We contrast the performance of ten machine learning classifiers experimented on two real IoT datasets and their fake adversarial samples. Our work highlights a vulnerable side of NIDS created by machine learning when attacked with adversarial perturbation.

Research has been conducted on solid oxide fuel cells (SOFCs) for their fuel flexibility, modularity, high efficiency, and power density. However, the high working temperature leads to the deterioration of materials and increased operating costs. Considering the high protonic conductivity and low activation energy, the proton conducting SOFC, i.e., the protonic ceramic fuel cell (PCFC), working at a low temperature, has been wildly investigated. The PCFC is a promising state-of-the-art electrochemical energy conversion system for ecological energy; it is characterized by near zero carbon emissions and high efficiency, and it is environment-friendly. The PCFC can be applied for the direct conversion of various renewable fuels into electricity at intermediate temperatures (400–650 °C). The construction of the PCFC directly affect its properties; therefore, manufacturing technology is the crucial factor that determines the performance. As a thinner electrolyte layer will lead to a lower polarization resistance, a uniformly constructed and crack-free layer which can perfectly bond to electrodes with a large effective area is challenging to achieve. In this work, different fabrication methods are investigated, and their effect on the overall performance of PCFCs is evaluated. This article reviews the recent preparation methods of PCFCs, including common methods, 3D printing methods, and other advanced methods, with summarized respective features, and their testing and characterization results.

Background and aimsCuproptosis has been identified as a key player in the development of several diseases. In this study, we investigate the potential role of cuproptosis-related genes in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).MethodThe gene expression profiles of NAFLD were obtained from the Gene Expression Omnibus database. Differential expression of cuproptosis-related genes (CRGs) were determined between NAFLD and normal tissues. Protein–protein interaction, correlation, and function enrichment analyses were performed. Machine learning was used to identify hub genes. Immune infiltration was analyzed in both NAFLD patients and controls. Quantitative real-time PCR was employed to validate the expression of hub genes.ResultsFour datasets containing 115 NAFLD and 106 control samples were included for bioinformatics analysis. Three hub CRGs (NFE2L2, DLD, and POLD1) were identified through the intersection of three machine learning algorithms. The receiver operating characteristic curve was plotted based on these three marker genes, and the area under the curve (AUC) value was 0.704. In the external GSE135251 dataset, the AUC value of the three key genes was as high as 0.970. Further nomogram, decision curve, calibration curve analyses also confirmed the diagnostic predictive efficacy. Gene set enrichment analysis and gene set variation analysis showed these three marker genes involved in multiple pathways that are related to the progression of NAFLD. CIBERSORT and single-sample gene set enrichment analysis indicated that their expression levels in macrophages, mast cells, NK cells, Treg cells, resting dendritic cells, and tumor-infiltrating lymphocytes were higher in NAFLD compared with control liver samples. The ceRNA network demonstrated a complex regulatory relationship between the three hub genes. The mRNA level of these hub genes were further confirmed in a mouse NAFLD liver samples.ConclusionOur study comprehensively demonstrated the relationship between NAFLD and cuproptosis, developed a promising diagnostic model, and provided potential targets for NAFLD treatment and new insights for exploring the mechanism for NAFLD.

Cancer represents a challenging medical problem worldwide. Several exploratory studies have been conducted to overcome these limitations. RNA vaccines play an important role in cancer prevention and treatment. Recent studies have shown that RNA vaccines play an important role in cancer prevention. However, there are currently no relevant bibliometric studies. This study aimed to apply bibliometrics to summarize the knowledge structure and research hotspots regarding the role of RNA vaccines in cancer. Publications related to RNA vaccines in cancer were searched on the web of science core collection (WoSCC) database. VOSviewers, CiteSpace and R package “bibliometrix” were used to conduct this bibliometric analysis. A total of 1399 articles were included, comprising 803 original articles and 596 reviews. The number of studies on RNA vaccines against cancer has been increasing annually. China and the United States were the principal countries of origin of publications. Johannes Gutenberg University Mainz, NCI, and Duke University were the main organizations. Frontiers in Immunology is the leading journal in the field. Hot keywords included tumor antigens, lipid nanoparticles, emerging roles, and dendritic cells. This is the bibliometric study to summarize the research trends and development of RNA vaccines for cancer. This information will provide a reference for researchers studying RNA vaccines against cancer.

Neuro-navigation is a key technology to ensure the clinical efficacy of TMS. However, the neuro-navigation system based on positioning sensor is currently unable to be promoted and applied in clinical practice due to its time-consuming and high-cost. In the present study, we designed I-Helmet system to promote an individualized and clinically friendly neuro-navigation approach to TMS clinical application. I-Helmet system is based on C++ with a graphical user interface that allows users to design a 3D-printed helmet model for coil navigation. Besides, a dedicated coil positioning accuracy detection method was promoted based on three-dimensional (3D) printing and 3D laser scanning for evaluation. T1 images were collected from 24 subjects, and based on each image, phantom were created to simulate skin and hair. Six 3D-printed helmets with the head positioning hole enlarged by 0–5% tolerance in 1% increments were designed to evaluate the influences of skin, hair, and helmet-tolerance on the positioning accuracy and contact force of I-Helmet. Finally, I-Helmet system was evaluated by comparing its positioning accuracy with three skin hardnesses, three hair styles, three operators, and with or without landmarks. The accuracy of the proposed coil positioning accuracy detection method was about 0.30 mm in position and 0.22° in orientation. Skin and hair had significant influences on positioning accuracy (p 0.05). The tolerance of the helmet presented significant influences on positioning accuracy (p

Abstract As an economically important legume, Vicia sativa is commonly used as fodder for livestock and in health‐promoting foods for human consumption; however, cold stress is one of the most important limitations to its utilization at high altitudes. The shoot tissues of three cold‐resistant (Lan1, Lan2, and Lan3) and three cold‐sensitive (368, 521, and 538) accessions were collected after cold (4°C) treatment for 0, 6, and 48 h to assess their molecular regulatory mechanisms during cold stress via integrative analyses of their transcriptomes and metabolomes. Our Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that the biosynthesis of phenylpropanoids was the most enriched pathway in the cold stress response of V. sativa. A total of 18 differential metabolites were obtained in the biosynthesis of the phenylpropanoid pathway, and 722 differentially expressed genes (DEGs) showed a significant positive correlation with naringenin and p‐coumaric acid following a weighted gene co‐expression network analysis, while 84 DEGs showed significant negative associations. Moreover, four DEGs were overexpressed in yeast, and it was indicated that their biological function is to confer cold tolerance. These results provide a valuable resource for understanding the underlying molecular mechanism of V. sativa's response to cold stress and furthering the development of breeding research.

Background and objectiveIt has been proved that repetitive transcranial magnetic stimulation (rTMS) triggers the modulation of homeostatic metaplasticity, which causes the effect of rTMS to disappear or even reverse, and a certain length of interval between rTMS trains might break the modulation of homeostatic metaplasticity. However, it remains unknown whether the effects of high-frequency rTMS can be modulated by homeostatic metaplasticity by lengthening the train duration and whether homeostatic metaplasticity can be broken by prolonging the inter-train interval.MethodsIn this study, 15 subjects participated in two experiments including different rTMS protocols targeting the motor cortex. In the first experiment, high-frequency rTMS protocols with different train durations (2 s and 5 s) and an inter-train interval of 25 s were adopted. In the second experiment, high-frequency rTMS protocols with a train duration of 5 s and different inter-train intervals (50 s and 100 s) were adopted. A sham protocol was also included. Changes of motor evoked potential amplitude acquired from electromyography, power spectral density, and intra-region and inter-region functional connectivity acquired from electroencephalography in the resting state before and after each rTMS protocol were evaluated.ResultsHigh-frequency rTMS with 2 s train duration and 25 s inter-train interval increased cortex excitability and the power spectral density of bilateral central regions in the alpha frequency band and enhanced the functional connectivity between central regions and other brain regions. When the train duration was prolonged to 5 s, the after-effects of high-frequency rTMS disappeared. The after-effects of rTMS with 5 s train duration and 100 s inter-train interval were the same as those of rTMS with 2 s train duration and 25 s inter-train interval.ConclusionOur results indicated that train duration and inter-train interval could induce the homeostatic metaplasticiy and determine the direction of intensity of rTMS after-effects, and should certainly be taken into account when performing rTMS in both research and clinical practice.

Abstract Genome editing is an advanced genetic modification tool that facilitates the removal, insertion, or substitution of nucleotides in the genome of an organism for mutation induction. CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR‐associated protein 9) is the most widely used genome editing tool that can precisely modify the specific sequence of a genome. Significant progress has been made in the use of CRISPR/Cas9 for the genetic improvement of food crops. However, in forage crops, the use of CRISPR/Cas9 is still in the infant stage with limited understanding and application. This article reviews current advances in the establishment and application of the CRISPR/Cas9 system in alfalfa, summarizes the application of CRISPR/Cas9 in several other forage legume and grass species, and discusses the prospects of CRISPR/Cas9 in the genetic improvement of forage crops.

Semi-continuous anaerobic digestion (AD) of food waste (FW) was conducted by solar intelligent control system to explore the impact of temperature fluctuation on microorganisms and its engineering applicability. According to analysis of the AD system at different organic loading rate (OLR), introduction of the solar intelligent control system into AD could save electric energy. Temperature fluctuation caused by climate and other factors reduced methane production by 31.79%. Before reaching the optimum OLR, the methane yield increased with the promotion of OLR and was at the optimum when OLR = 4.5 kg ⋅ m−3 ⋅ d−1. Enzyme activities changed with the change of pH. Lower pH limited the enzyme activities. At the initial stage of the reaction, Clostridium and Lactobacillus dominated, which made content of amylase and lipase reach 264.07 U/mL (solar group), 331.02 U/mL (electric group), and 276.44 U/mL (solar group), 306.75 U/mL (electric group), respectively. Temperature fluctuation brought in by the solar intelligent control system had a great effect on microbial activity. Microbial community structure was influenced by the OLR change. Methanobacterium became the main methanogenic bacterium at the middle and late stage. After analysis, it is feasible to introduce solar energy into AD.

Abstract Bionic self‐cleaning coatings have exhibited scaling inhibition for their low surface free energy. The key issue is focused on the long‐term anti‐scaling performance for the hydrophobicity failure after scaled. Inspired by “grass‐to‐stone” phenomenon, we reported a polymer coating (WCA = 120°, WSA = 14°) with the water contact angle of its 720 h‐scaled surface increased to 135°and scaling reduced by 90–95%. The nucleation and growth of CaCO3 at “coating‐crystal” interface are investigated, and a physical model for self‐healing film interface inhibiting scaling is innovatively proposed, as an important step toward designing long‐term anti‐scaling coating for engineering application.

Abstract Background Alfalfa (Medicago sativa) is a widely cultivated plant. Unlike many crops, the main goal of breeding alfalfa is to increase its aboveground biomass rather than the biomass of its seeds. However, the low yield of alfalfa seeds limits alfalfa production. Many studies have explored the factors affecting seed development, in which phytohormones, especially ABA and GAs, play an important role in seed development. Results Here, we performed a transcriptome analysis of alfalfa seeds at five development stages. A total of 16,899 differentially expressed genes (DEGs) were identified and classified into 10 clusters, and the enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined. The contents of ABA, GA1, GA3, GA4 and GA7 in alfalfa seeds at five development stages were determined. In addition, 14 ABA-related DEGs and 20 GA-related DEGs were identified and analysed. These DEGs are involved in plant hormone pathways and play an important role in seed development. Moreover, morphological and physiological analyses revealed the dynamic changes during the development of alfalfa seeds. Conclusion Overall, our study is the first to analyse the transcriptome across various stages of seed development in alfalfa. The results of our study could be used to improve alfalfa seed yield. The key ABA and GA related-genes are potential targets for improving alfalfa seed yield via genetic engineering in the future.

As the second most abundant natural polymer, accounting for approximately 30% of the organic carbon in the biosphere, lignin plays an essential role in plant development. However, a high lignin content affects the nutritional quality of alfalfa (Medicago sativa L.), the most widely cultivated perennial legume forage crop. Histological analysis indicated that G-lignin and S-lignin were present in the stem, leaf, and petiole of alfalfa, and the deposition of lignin increased gradually in descending internodes. Neutral detergent fiber (NDF), acid detergent fiber (ADF), and acid detergent lignin (ADL) contents continually increased from the top to the bottom of the stem, and ADL content showed a similar trend in leaves. Alfalfa leaves and stems from five different nodes (1, 2, 4, 6, and 8) were used as materials to investigate molecular regulatory mechanisms in lignin synthesis by RNA sequencing. Respectively 8074 and 7752 differentially expressed genes (DEGs) were identified in leaves and stems, and 1694 DEGs were common to the two tissues. “Phenylpropanoid biosynthesis” was the most enriched pathway in both leaves and stems, and 134 key regulatory genes in lignin synthesis were identified by a weighted gene co-expression network analysis. The NAC family transcription factor MsNST1 gene was highly expressed in old leaf and stem tissues. The deposition pattern of G- and S-lignin differed among M. truncatula wild-type, nst1 mutants, and overexpression lines, and the transcription levels of lignin synthesis genes such as HCT, F5H, and COMT in these three materials also differed. These results suggest that MsNST1 affects lignin synthesis in alfalfa. These findings provide a genetic basis and abundant gene resources for further study of the molecular mechanisms of lignin synthesis, laying a foundation for low-lignin alfalfa breeding research.

Aiming at the application requirements on a variety of complex roads and based on the biological metamorphosis mechanism，a wheel-tracked reconfigurable robot is proposed. The robot includes two motion modes，namely wheel mode and crawler mode. By switching between the two modes，the adaptability of the robot on multiple ground features can be significantly improved. The study of switching mechanism and transmission principle is carried out. The changing trend of the contact width is analyzed to obtain a maximum value of 230.36 mm in crawler mode. The robot's ability to overcome obstacles in wheel and crawler modes is calculated separately，and the trend of the robot's center of gravity position during obstacle-crossing is analyzed through simulation software. Finally，a prototype of the robot is developed by integrating the power system. Wooden boards and hollow bricks with different heights as experimental platforms are used to test the robot's mode-switch and obstacle crossing ability in groups. The experimental results show the maximum obstacle crossing heights in wheel and crawler modes are 98.5 mm and 290 mm which are consistent with the theoretical value. In addition，the robot can flexibly switch between wheel mode and crawler modes，which has the ability to adapt to a variety of complex roads.

Abstract Background Cathelicidin/LL-37 plays a significant role in the human immune defense reaction. Preterm human immature organs being exposed to inflammation-induced injury was the critical denominator leading to the common preterm associated complications. Previous study showed LL37 concentration in preterm neonates was lower in tracheal aspirates and breast milk as compared to term infants. An adults study showed decreased LL-37 levels was a risk factor for patients in developing severe chronic obstructive pulmonary disease (COPD). However, little is known about the regulation of human cord blood LL37 in preterm neonates and the association with preterm complications. This study was designed to investigate the concentration of LL37 in cord blood of preterm infants and correlation with preterm complications. Methods Singleton infants born in June 2017 to August 2021 in the study hospital were enrolled. Maternal and neonatal clinical characteristics were collected. LL37 levels, pro-inflammatory factor interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in cord blood and LL37 levels in serum 48–72 hours after birth were measured by enzyme-linked immunosorbent assay. The serum level of LL37 in preterm and term neonates were compared, the perinatal factors possibly affecting the LL37 levels were investigated and the relationship between LL37 level and preterm outcomes were analyzed. Results Cord blood LL37 levels in preterm infants were lower than that in term neonates. Cord blood LL37 level was positively correlated with gestational age in preterm. Prenatal steroid administration in preterm neonates decreased cord blood LL37 level. LL37 level was obviously lower in patients with bronchopulmonary dysplasia (BPD). Multiple line regression analysis showed higher LL37 level in cord blood was an independent protective factor for BPD. The concentration of pro-inflammatory factor IL-6 was negatively correlated with LL37. Conclusion Cord blood LL37 levels increased during gestation and decreased after perinatal steroid usage. Very preterm infants who displayed higher cord blood LL37 level had reduced risk of developing BPD. Regulation of pro-inflammatory cytokine IL-6 may be associated with the protective effect of LL37 on BPD.

Abstract In this work, a simple anti‐fingerprint strategy (reduced ≈40–60%) to rearrange fingerprint droplets by patterned micro/nano‐pore/spoons texture, air cushion and low surface energy is reported. Superior to previous precise and complex preparation methods, the micro/nano‐texture are fabricated through conventional process of spray and dip. The pore and spoon can be freely switched by changing the process. The number (N) and size (r) of pores and spoons are controlled intelligently by solvent volatilization and interfacial tension (γFP/PU−H2O and γFP/PU − Solvent), the key for pore/spoon's forming and expanding. A physical model of interface intelligent controlling the micro/nano‐pore/spoon surface texture induced by “Vacancy‐Capture” is proposed. The description is being reported, for the first time, to the knowledge, expecting to make it possible to prepare anti‐fingerprint engineering materials with newly potential industrial applications on optical device for large‐scale in the future.

This study investigated the effects of subchronic arsenic exposure on behavior, neurological function, and hippocampal damage in rats. Thirty-two male Wistar rats were divided into four groups and exposed to different concentrations of arsenic in their drinking water for 12 weeks, while weekly water intake and body weight were recorded. Various neurobehavioral tests were conducted, evaluating overall activity levels, exploratory behavior, short-term memory, spatial learning and memory, anxiety-like behavior, and depressive-like states. Arsenic levels in urine, serum, and brain tissue were measured, and histopathological analysis assessed hippocampal damage using hematoxylin and eosin staining. The results demonstrated that arsenic exposure did not significantly affect overall activity or exploratory behavior. However, it impaired short-term memory and spatial learning and memory functions. Arsenic-exposed rats exhibited increased anxiety-like behavior and a depressive-like state. Arsenic levels increased dose-dependently in urine, serum, and brain tissue. The histopathological examinations revealed significant hippocampal damage, including neuronal shrinkage, cell proliferation, irregular structure, disordered arrangement, and vacuolation. These findings emphasize the importance of understanding the impact of arsenic exposure on behavior and brain health, highlighting its potential neurological consequences.

The successful establishment of endometrial receptivity is a key factor in ensuring the fertility of ewes and their economic benefits. Hu sheep have attracted attention due to their high fecundity and year-round estrus. In this study, we found that in the luteal phase, the uterine gland density, uterine coefficient, and number of uterine caruncles of high-fertility Hu sheep were higher than those of low-fertility Hu sheep. Thousands of differentially expressed genes were identified in the endometrium of Hu sheep with different fertility potential using RNA sequencing (RNA-Seq). Several genes involved in endometrial receptivity were screened using bioinformatics analysis. The qRT-PCR analysis further revealed the differential expression of cAMP reactive element binding protein-1 (CREB1) in the Hu sheep endometrium during the estrous cycle. Functionally, our results suggested that CREB1 significantly affected the expression level of endometrial receptivity marker genes, promoted cell proliferation by facilitating the transition from the G1 phase to the S phase, and inhibited cell apoptosis and autophagy. Moreover, we observed a negative linear correlation between miR-134-5p and CREB1 in the endometrium. In addition, CREB1 overexpression prevented the negative effect of miR-134-5p on endometrial stromal cell (ESC) growth. Taken together, these data indicated that CREB1 was regulated by miR-134-5p and may promote the establishment of uterine receptivity by regulating the function of ESCs. Moreover, this study provides new theoretical references for identifying candidate genes associated with fertility.

Precision exogenous gene knock-in is an attractive field for transgenic Gallus gallus (chicken) generation. In this article, we constructed multiple Precise Integration into Target Chromosome (PITCh) plasmid systems mediated by microhomology-mediated end-joining (MMEJ) for large-fragment integration in DF-1 cells and further assess the possibility of GAPDH (glyceraldehyde-3-phosphate dehydrogenase) as a genomic safe harbor for chickens. We designed three targeted sgRNAs for the all-in-one plasmid at the 3′UTR of GAPDH near the stop codon. The donor-plasmid-carrying microhomology arms correspond to sgRNA and EGFP fragments in the forward and reverse directions. MMEJ-mediated EGFP insertion can be efficiently expressed in DF-1 cells. Moreover, the differences between the forward and reverse fragments indicated that promoter interference does affect the transfection efficiency of plasmids and cell proliferation. The comparison of the 20 bp and 40 bp microhomology arms declared that the short one has higher knock-in efficiency. Even though all three different transgene insertion sites in GAPDH could be used to integrate the foreign gene, we noticed that the G2-20R-EGFP cell reduced the expression of GAPDH, and the G3-20R-EGFP cell exhibited significant growth retardation. Taken together, G1, located at the 3′UTR of GAPDH on the outer side of the last base of the terminator, can be a candidate genomic safe harbor (GSH) loci for the chicken genome. In addition, deleted-in-azoospermia-like (DAZL) and actin beta (ACTB) site-specific gene knock-in indicated that MMEJ has broad applicability and high-precision knock-in efficiency for genetically engineered chickens.

Abstract T cell immunotherapy remains an attractive approach for cancer immunotherapy. T cell immunotherapy mainly employs chimeric antigen receptor (CAR)- and T cell receptor (TCR)-engineered T cells. CAR-T cell therapy has been an essential breakthrough in treating hematological malignancies. TCR-T cells can recognize antigens expressed both on cell surfaces and in intracellular compartments. Although TCR-T cells have not been approved for clinical application, a number of clinical trials have been performed, particularly for solid tumors. In this article, we summarized current TCR-T cell advances and their potential advantages for solid tumor immunotherapy.

Here, Wang and colleagues combine short and long sequencing reads to characterize structural variations, prophage and CRISPR spacer elements in human gut microbiomes, and reveal functional differences at a finer level of bacterial strains.

The graphene oxide-silica, GO-SiO2 (GS) nanoparticles synthesized by in-situ hydrolysis were grafted with block polymers polyethylene glycol (PEG) and low-molecular polyethylene terephthalate (LPET) using 3-isocyanatopropyltrimethicone (IPTES) as a bridge to prepare the additive GS-IPTES plus PEG-LPET (GSIP). This grafting process was confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The GSIP of various contents was used as reinforcing fillers to prepare PET/GSIP composite by melt blending. The crystallization and mechanical properties of the PET/GSIP composite were dramatically enhanced with the addition of small amounts of GSIP. Compared with pure PET, the crystallization temperature of PET/GSIP was increased by 41 °C at 1 wt.% addition of GSIP. Moreover, the highest tensile strength was 91.2 MPa and the highest modulus was 14.7 GPa at 0.8 wt.% addition. The crystalline and mechanical properties improvements were attributed to the synergistic effects of GS and block polymer chains.

Abstract Background Lots of studies have measured motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) in anesthetized animals. However, in awake animals, the measurement of TMS-induced MEP is scarce as lack of sufficient restraint. So far, the explicit study of anesthesia effects on corticospinal excitability and repetitive TMS (rTMS) induced modulation is still lacking. This study aimed to: (1) measure TMS-induced MEP in both awake restrained and anesthetized rats, (2) investigate the effect of anesthesia on corticospinal excitability, and (3) on rTMS-induced modulation. Methods MEP of eighteen rats were measured under both wakefulness and anesthesia using flexible binding and surface electrodes. Peak-to-peak MEP amplitudes, resting motor threshold (RMT) and the slope of stimulus response (SR) were extracted to investigate anesthesia effects on corticospinal excitability. Thereafter, 5 or 10 Hz rTMS was applied with 600 pulses, and the increase in MEP amplitude and the decrease in RMT were used to quantify rTMS-induced modulation. Results The RMT in the awake condition was 44.6 ± 1.2% maximum output (MO), the peak-to-peak MEP amplitude was 404.6 ± 48.8 μV at 60% MO. Under anesthesia, higher RMT (55.6 ± 2.9% MO), lower peak-to-peak MEP amplitudes (258.6 ± 32.7 μV) and lower slope of SR indicated that the corticospinal excitability was suppressed. Moreover, under anesthesia, high-frequency rTMS still showed significant modulation of corticospinal excitability, but the modulation of MEP peak-to-peak amplitudes was weaker than that under wakefulness. Conclusions This study measured TMS-induced MEP in both awake and anesthetized rats, and provided explicit evidence for the inhibitory effects of anesthesia on corticospinal excitability and on high-frequency rTMS-induced modulation of MEP.

Very thin free-flowing liquid sheets are promising targets for high-repetition-rate laser-ion acceleration. In this work, we report the generation of micrometer-thin free-flowing liquid sheets from the collision of two liquid jets, and study the vibration and jitter in their surface normal direction. The dependence of their motion amplitudes on the generation parameters is studied in detail. The origins of the vibration and jitter are discussed. Our results indicate that when the generation parameters are optimized, the motion amplitudes in the stable region can be stabilized below 3.7 μm to meet the stringent requirement of sheet position stability for a tight-focusing setup in laser-ion acceleration experiments.

As important components of the two-component regulatory system, response regulatory proteins (RRPs) play a crucial role in histidine phosphorylation-mediated signal transduction in response to environmental fluctuations. Accumulating evidence has revealed that RRPs play important roles in plant growth and stress response. However, the specific functions of RR genes (RRs) in cultivated alfalfa remain ambiguous. Therefore, in this study, we identified and characterized the RR family genes in the alfalfa genome using bioinformatics methods. Our analysis revealed 37 RRs in the alfalfa genome of Zhongmu No.1 that were unevenly distributed on the chromosomes. Cis-elements analysis revealed the involvement of RRs in responses to light, stress, and various plant hormones. Expression analysis of RRs in different tissues revealed their distinct tissue expression patterns. These findings provide preliminary insights into the roles of RRs in plant responses to abiotic stress, which can be used to improve the stress tolerance of autotetraploid-cultivated alfalfa plants via genetic engineering.

The neuropathological features of Alzheimer’s disease include amyloid plaques. Rapidly emerging evidence suggests that Piezo1, a mechanosensitive cation channel, plays a critical role in transforming ultrasound-related mechanical stimuli through its trimeric propeller-like structure, but the importance of Piezo1-mediated mechanotransduction in brain functions is less appreciated. However, apart from mechanical stimulation, Piezo1 channels are strongly modulated by voltage. We assume that Piezo1 may play a role in converting mechanical and electrical signals, which could induce the phagocytosis and degradation of Aβ, and the combined effect of mechanical and electrical stimulation is superior to single mechanical stimulation. Hence, we design a transcranial magneto-acoustic stimulation (TMAS) system, based on transcranial ultrasound stimulation (TUS) within a magnetic field that combines a magneto-acoustic coupling effect electric field and the mechanical force of ultrasound, and applied it to test the above hypothesis in 5xFAD mice. Behavioral tests, in vivo electrophysiological recordings, Golgi–Cox staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, real-time quantitative PCR, Western blotting, RNA sequencing, and cerebral blood flow monitoring were used to assess whether TMAS can alleviate the symptoms of AD mouse model by activating Piezo1. TMAS treatment enhanced autophagy to promote the phagocytosis and degradation of β-amyloid through the activation of microglial Piezo1 and alleviated neuroinflammation, synaptic plasticity impairment, and neural oscillation abnormalities in 5xFAD mice, showing a stronger effect than ultrasound. However, inhibition of Piezo1 with an antagonist, GsMTx-4, prevented these beneficial effects of TMAS. This research indicates that Piezo1 can transform TMAS-related mechanical and electrical stimuli into biochemical signals and identifies that the favorable effects of TMAS on synaptic plasticity in 5xFAD mice are mediated by Piezo1.

Post-acceleration of protons in helical coil targets driven by intense, ultrashort laser pulses can enhance ion energy by utilizing the transient current from the targets’ self-discharge. The acceleration length of protons can exceed a few millimeters, and the acceleration gradient is of the order of GeV/m. How to ensure the synchronization between the accelerating electric field and the protons is a crucial problem for efficient post-acceleration. In this paper, we study how the electric field mismatch induced by current dispersion affects the synchronous acceleration of protons. We propose a scheme using a two-stage helical coil to control the current dispersion. With optimized parameters, the energy gain of protons is increased by four times. Proton energy is expected to reach 45 MeV using a hundreds-of-terawatts laser, or more than 100 MeV using a petawatt laser, by controlling the current dispersion.

In this present work, cement slurry flowing in well annuli with narrow or varied radial sizes is investigated, whose purpose is to precisely calculate the equivalent circulating density (ECD) during well cementing in the petroleum industry. The theoretical Metzner-Reed (MR) method and the direct numerical simulation (DNS) are applied to calculate the cementing ECD for different types of cement slurries by considering both the Bingham and Power-Law rheological models. The cementing ECD calculated by the theoretical MR method is verified to be in accordance with the DNS result. Moreover, for the narrow annulus, the cementing ECD is demonstrated to be sensitive to the rheological model. In addition, based on the obtained DNS results, the accuracies of the cementing ECD calculated by three commercial software, including DRILL BENCH (DB), LANDMARK (LM), and PVI, are compared, to determine their corresponding adaptability for different rheological models. According to the detailed comparisons, LM shows the highest accuracy in calculating the cementing ECD for the Power-Law fluid, while PVI is optimal for the Bingham fluid. However, sharp fluctuations of the calculation errors are observed when DB is applied.

IntroductionPhysical fitness is an essential part of a healthy lifestyle that concerns the overall health of the nation. Research on the relationship between the Internet and physical fitness has long been caught in the dilemma of “media mobilization” and “media suppression,” and previous studies have rarely examined the causal relationship and functional mechanism.MethodsThis study selected the data of 23,989 samples successfully followed in all three surveys of the China Family Panel Survey (CFPS) from 2014 to 2018 to explore the correlation and causal inference between the Internet and physical fitness by using the Time Fixed Effects Model and cross-lagged models, respectively; meanwhile, the data of 24,687 samples in CFPS 2020 to examine the functional mechanism of the Internet's effect on residents' physical fitness behavior by the KHB method.ResultsWe obtained three valuable conclusions as follows: First, there is a significant correlation between the Internet and physical fitness behavior. Second, the Internet use is the cause for the increase in fitness frequency, and there is a rival relationship between Internet duration and fitness time. Third, under regular prevention and control of the COVID-19 epidemic, social capital and health risk perceptions are the functional mechanisms of the Internet influencing fitness behavior, and the mediating effect of psychological health risk perceptions is higher than that of social capital.DiscussionIt's necessary to create an intelligent, informative, and digital sports public service system by enriching and optimizing sports media and facilitating the Internet to serve residents' physical fitness better. The new concept of “Internet plus Fitness” will be of great significance in the implementation of the “Healthy China Initiative.”