VmSom1 is Essential for Growth, Development, Maintenance of Cell Wall Integrity and Virulence in Valsa mali.

Apple Valsa canker disease, caused by Valsa mali Miyabe et Yamada, severely endangers the healthy growth of apple trees. The Som1, located downstream of the cyclic AMP-dependent protein kinase A (cAMP-PKA) pathway, plays crucial roles in the growth, development, morphological differentiation, and virulence of filamentous fungi. In this study, we identify and functionally characterize VmSom1, a homolog of Som1, in Valsa mali. The VmSom1 gene is located on chromosome 12, encoding an 824 amino acid protein. Phylogenetic analysis reveals VmSom1 as a fungal Som1 homolog. The VmSom1 deletion mutants exhibit slower growth rates and fail to produce pycnidia. Additionally, their hyphal growth is significantly inhibited on media containing Calcofluor White, Congo Red, NaCl, and sorbitol. The growth rate of VmSom1 deletion mutants is reduced on maltose, lactose, sucrose and fructose media but increases on glucose medium. Moreover, the mycelial growth rate of the VmSom1 deletion mutant is significantly lower than that of the wild-type strain in peptone, NH4SO4, NaNO3, and no nitrogen. Notably, the distances between the septa increase, and chitin concentration shifts to the hyphal tip in the VmSom1 deletion mutant. Furthermore, compared with the wild-type strain, the VmSom1 deletion mutant exhibits fewer diseased spots on apple fruit and branches. Overall, our findings demonstrate that VmSom1 is involved in regulating the growth and development, colony surface hydrophobicity, osmotic stress, cell wall integrity maintenance, carbon and nitrogen source utilization, septa formation, and virulence of V. mali.

Oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles attenuates gastric and small intestinal mucosal ferroptosis caused by hypoxia through inhibiting HIF-1α- and HIF-2α-mediated lipid peroxidation.

The prevention and treatment of gastrointestinal mucosal injury caused by a plateau hypoxic environment is a clinical conundrum due to the unclear mechanism of this syndrome; however, oxidative stress and microbiota dysbiosis may be involved. The Robinia pseudoacacia L. flower, homologous to a functional food, exhibits various pharmacological effects, such as antioxidant, antibacterial, and hemostatic activities. An increasing number of studies have revealed that plant exosome-like nanoparticles (PELNs) can improve the intestinal microbiota and exert antioxidant effects. In this study, the oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles (RFELNs) significantly ameliorated hypoxia-induced gastric and small intestinal mucosal injury in mice by downregulating hypoxia-inducible factor-1α (HIF-1α) and HIF-2α expression and inhibiting hypoxia-mediated ferroptosis. In addition, oral RFELNs partially improved hypoxia-induced microbial and metabolic disorders of the stomach and small intestine. Notably, RFELNs displayed specific targeting to the gastrointestinal tract. In vitro experiments using gastric and small intestinal epithelial cell lines showed that cell death caused by elevated HIF-1α and HIF-2α under 1% O2 mainly occurred via ferroptosis. RFELNs obviously inhibited HIF-1α and HIF-2α expression and downregulated the expression of NOX4 and ALOX5, which drive reactive oxygen species production and lipid peroxidation, respectively, suppressing ferroptosis under hypoxia. In conclusion, our findings underscore the potential of oral RFELNs as novel, naturally derived agents targeting the gastrointestinal tract, providing a promising therapeutic approach for hypoxia-induced gastric and small intestinal mucosal ferroptosis.

Lignin/Surfactin Coacervate as an Eco-Friendly Pesticide Carrier and Antifungal Agent against Phytopathogen.

Excessive usage of biologically toxic fungicides and their matrix materials poses a serious threat to public health. Leveraging fungicide carriers with inherent pathogen inhibition properties is highly promising for enhancing fungicide efficacy and reducing required dosage. Herein, a series of coacervates have been crafted with lignin and surfactin, both of which are naturally derived and demonstrate substantial antifungal properties. This hierarchically assembled carrier not only effectively loads fungicides with a maximum encapsulation efficiency of 95% but also stably deposits on hydrophobic leaves for high-speed impacting droplets. Intriguingly, these coacervates exhibit broad spectrum fungicidal activity against eight ubiquitous phytopathogens and even act as a standalone biofungicide to replace fungicides. This performance can significantly reduce the fungicide usage and be further strengthened by an encapsulated fungicide. The inhibition rate reaches 87.0% when 0.30 mM pyraclostrobin (Pyr) is encapsulated within this coacervate, comparable to the effectiveness of 0.80 mM Pyr alone. Additionally, the preventive effects against tomato gray mold reached 53%, significantly surpassing those of commercial adjuvants. Thus, it demonstrates that utilizing biosurfactants and biomass with intrinsic antifungal activity to fabricate fully biobased coacervates can synergistically combine the functions of a fungicide carrier and antifungal agent against phytopathogens and guarantee environmental friendliness. This pioneering approach provides deeper insights into synergistically enhancing the effectiveness of agrochemicals from multiple aspects, including fungicide encapsulation, cooperative antifungal action, and droplet deposition.

Variable and interactive effects of Sex, APOE ε4 and TREM2 on the deposition of tau in entorhinal and neocortical regions.

The canonical AD pathological cascade posits that the accumulation of amyloid beta (Aß) is the initiating event, accelerating the accumulation of tau in the entorhinal cortex (EC), which subsequently spreads into the neocortex. Here in a sample of over 1300 participants with multimodal imaging and genetic information we queried how genetic variation affects these stages of the AD cascade. We observed that females and APOE-ε4 homozygotes are more susceptible to the effects of Aß on the primary accumulation of tau, with greater EC tau for a given level of Aß. Furthermore, we observed for individuals who have rare risk variants in Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) and/or APOE-ε4 homozygotes there was a greater spread of primary tau from the EC into the neocortex. These findings offer insights into the function of sex, APOE and microglia in AD progression, and have implications for determining personalised treatment with drugs targeting Aß and tau.

Nanoparticle-mediated calmodulin dsRNA and cyantraniliprole co-delivery system: High-efficient control of two key pear pests while ensuring safety for natural enemy insects.

Currently, the predominant method for managing pests in orchards is chemical control. However, prolonged use of chemicals leads to resistance issues and raise ecological safety. A promising approach to tackle these challenges involves nanoparticles-mediated delivery system of dsRNA and pesticides. Despite its potential, this strategy has not been widely applied in controlling pests in pear orchards. In this study, we developed a nanoparticle-mediated ternary biopesticide to tackle resistance and safety concerns associated with calmodulin dsRNA and cyantraniliprole. Initially, we assessed the effectiveness of cyantraniliprole against two key pear pests, Grapholita molesta and Cacopsylla chinensis. Subsequently, we observed an upregualtion of genes CaM and CN following cyantraniliprole treatment. Furthermore, inhibiting or silencing GmCaM and CcGaM enhanced the sensitivity to cyantraniliprole more effectively. By introducing hairpin RNA into the pET30a-BL21 RNaseIII- system to silence GmCaM and CcCaM, we developed a nanoparticle-mediated co-delivery system that exhibited improved control over these two pests. Importantly, our research demonstrated that using reduced cyantraniliprole dosages through ternary biopesticides could help mitigate risks to natural enemies. Overall, our research emphasizes the enhanced effectiveness of ternary biopesticides in boosting the performance of dsRNA and pesticide against pear pests, while fostering environmental sustainability-a novel advancement in this field.

A water-resistant egg white/chitosan/pectin blending film with spherical-linear molecular interpenetrating network strengthened by multifunctional tannin-nisin nanoparticles.

Edible films are effective alternatives to plastic packaging, however, the hydrophilicity of edible films based on protein and polysaccharide limits the application. Therefore, we fabricated a water-stable hybrid film with a linear-spherical interpenetrating molecular topology network using egg white (EW), chitosan (CS), and pectin. Meanwhile, the nisin-tannin acid self-assembly complex nanoparticles were employed as a multifunctional cross-linker, antibacterial and antioxidant agent to improve the performance of films. The FTIR, XRD, and SEM analysis revealed that the conformation and crystalline structure rearrangement of chitosan induced by the alkaline environment provided by egg white enhanced the network structure of films, effectively avoided the addition of modifying reagents. The proposed hybrid films exhibited excellent properties, with EW/TNPCS3 showing the best overall performance. The water contact angle (WCA) increased to 105.27 ± 1.62°, and its dissolution and swelling rates were significantly lower than pure egg white and pure chitosan films. Moreover, tannin-nisin (TN) nanoparticles endowed the films with excellent antimicrobial activity against the common Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Thus, the prepared blending films have great application potential in food preservation, especially to maintain stable performance in high humidity environment.

Low handgrip strength with asymmetry is associated with elevated all-cause mortality risk in older Chinese adults with abdominal obesity.

BACKGROUND AND OBJECTIVES: Low handgrip strength (HGS) and abdominal obesity (AO) have been reported to be linked to an increased all-cause mortality risk in older adults. However, the combined impact of AO with low HGS and/or HGS asymmetry on mortality risk remains unclear. Therefore, this study aimed to investigate the synergistic effects of AO and abnormal HGS on mortality risk among Chinese older adults. METHODS: Baseline data of the China Health and Retirement Longitudinal Study in 2011, along with mortality outcomes obtained in 2018 were used for the analysis. Low HGS was identified as HGS <18 kg in women or <28 kg in men, while HGS asymmetry is defined as an HGS of either hand > 10% stronger than the other. AO was characterized by a waist circumference ≥90 cm in men and ≥85 cm in women. Logistic regression analysis was used to evaluate the relationship between AO, abnormal HGS and mortality risk. RESULTS: A total of 5186 subjects aged 60 years or older were enrolled, 50.6% of whom were male. The proportions of participants with only AO, only low HGS, only HGS asymmetry, low HGS with asymmetry, both AO and low HGS, both AO and asymmetric HGS, and AO with both low HGS and asymmetry were 20.0%, 6.1%, 16.6%, 8.3%, 3.2%, 13.4%, and 3.9%, respectively. Over the course of a 7-year follow-up interval, 970 of these individuals died, with 13.4%, 12.4%, 13.6%, 15.5%, 4.1%, 10.1% and 6.9% of deaths in the above groups, respectively. The adjusted logistic regression analysis model confirmed that only low HGS (OR = 1.897, 95%CI: 1.386-2.596, p<0.001), low HGS with asymmetry (OR = 1.680, 95%CI: 1.265-2.231, p<0.001), and AO combined with both low HGS and asymmetry (OR = 2.029, 95%CI: 1.381-2.981, p<0.001) were associated with a higher risk of mortality. CONCLUSIONS: Low HGS, with or without asymmetry, is associated with increased mortality risk in older Chinese adults without AO, and the combination of low HGS and HGS asymmetry further elevates mortality risk in those with AO.

2D/3D hierarchical porous structure of mNPC/SMOH@C to construct an electrochemical sensor for the simultaneous determination of p-acetylaminophenol and p-aminophenol.

BACKGROUND: As persistent organic pollutants (POPs), the accumulation of p-acetylaminophenol (PAT) and p-aminophenol (PAP) in water can seriously damage the health of plants and animals, ultimately leading to threats to human health and safety. Electrochemical sensors have the advantages of being fast, inexpensive, and accurate compared to the complex, expensive, and cumbersome conventional analytical methods. In this study, we designed and synthesized composites with two-dimensional/three-dimensional (2D/3D) porous structures to construct an efficient electrochemical platform for the simultaneous detection of PAT and PAP. RESULTS: In this work, a novel 3D foamy birnessite Na0.55Mn2O4·1.5H2O@C (SMOH@C) was synthesized, which was composited with 2D ordered mesoporous nanosheets (mNPC) to construct electrochemical sensors detecting PAT and PAP simultaneously. The prepared 2D/3D porous structure of mNPC/SMOH@C increased the exposure of active sites due to its large specific surface area. The introduction of a 3D carbon skeleton altered the charge transfer rate of SMOH@C, and the rich pore structure and oxygen-rich vacancies created favorable conditions for the diffusion and adsorption of PAP and PAT, which enabled the sensitive detection of PAT and PAP. The constructed mNPC/SMOH@C electrochemical sensor could simultaneously detect PAT (1 × 10-7 - 1 × 10-4 M) and PAP (5 × 10-8 - 1 × 10-4 M) with detection limits of 20.4 nM and 30.1 nM, respectively. The sensor has good repeatability (RSD <4 %) and reproducibility (RSD <4 %), and satisfactory recoveries (96.7-102.8 %) were obtained in the analysis of natural water samples. SIGNIFICANCE: In this paper, for the first time, we present the synthesis of 3D foam birnessite and its composite with mNPC for the electrochemical simultaneous detection of PAT and PAP. Our proposed strategy for fabricating 2D/3D porous composites lays the foundation for the design and synthesis of other porous materials. In addition, this study provides new ideas for developing efficient and practical electrochemical sensors for detecting pollutants in aquatic environments.

Amplifying Radiotherapy by Evoking Mitochondrial Oxidative Stress Using a High-performance Aggregation-induced Emission Sonosensitizer.

INTRODUCTION: Developing effective methods to enhance tumor radiosensitivity is crucial for improving the therapeutic efficacy of radiotherapy (RT). Due to its deep tissue penetration, excellent safety profile, and precise controllability, sonosensitizer- based sonodynamic therapy (SDT) has recently garnered significant attention as a promising combined approach with RT. METHOD: However, the limited reactive oxygen species (ROS) generation ability in the aggregated state and the absence of specific organelle targeting in sonosensitizers hinder their potential to augment RT. This study introduces a fundamental principle guiding the design of high-performance sonosensitizers employed in the aggregated state. Building upon these principles, we develop a mitochondria-targeted sonosensitizer molecule (TCSVP) with aggregation-induced emission (AIE) characteristics by organic synthesis. Then, we demonstrate the abilities of TCSVP to target mitochondria and produce ROS under ultrasound in H460 cancer cells using confocal laser scanning microscopy (CLSM) and fluorescence microscopy. Subsequently, we examine the effectiveness of enhancing tumor radiosensitivity by utilizing TCSVP and ultrasound in both H460 cells and H460 and 4T1 tumor-bearing mice. RESULTS: The results indicate that evoking non-lethal mitochondrial oxidative stress in tumors by TCSVP under ultrasound stimulation can significantly improve tumor radiosensitivity (p <0.05). Additionally, the in vivo safety profile of TCSVP is thoroughly confirmed by histopathological analysis. CONCLUSION: This work proposes strategies for designing efficient sonosensitizers and underscores that evoking non-lethal mitochondrial oxidative stress is an effective method to enhance tumor radiosensitivity.

Access to Piperazine-Fused Pyrrolocarbazoles Enabled by Acid-Catalyzed Stereoselective Hydroarylation of Ynamide-Indoles and Subsequent Diels-Alder Reactions/Aromatizations.

Pyrrolocarbazole skeletons are well known to possess a variety of biological activities that might be therapeutically useful in the treatment of cancers. Herein, an acid-catalyzed stereoselective hydroarylation/Diels-Alder cycloaddition/aromatization of ynamide-indoles is described. We newly designed and synthesized a variety of piperazine-fused pyrrolocarbazole derivatives that could be further applied to the synthesis of potent Wee1 inhibitors.

Energy-Oriented Hybrid Cooperative Adaptive Cruise Control for Fuel Cell Electric Vehicle Platoons.

Given the complex powertrain of fuel cell electric vehicles (FCEVs) and diversified vehicle platooning synergy constraints, a control strategy that simultaneously considers inter-vehicle synergy control and energy economy is one of the key technologies to improve transportation efficiency and release the energy-saving potential of platooning vehicles. In this paper, an energy-oriented hybrid cooperative adaptive cruise control (eHCACC) strategy is proposed for an FCEV platoon, aiming to enhance energy-saving potential while ensuring stable car-following performance. The eHCACC employs a hybrid cooperative control architecture, consisting of a top-level centralized controller (TCC) and bottom-level distributed controllers (BDCs). The TCC integrates an eco-driving CACC (eCACC) strategy based on the minimum principle and random forest, which generates optimal reference velocity datasets by aligning the comprehensive control objectives of the platoon and addressing the car-following performance and economic efficiency of the platoon. Concurrently, to further unleash energy-saving potential, the BDCs utilize the equivalent consumption minimization strategy (ECMS) to determine optimal powertrain control inputs by combining the reference datasets with detailed optimization information and system states of the powertrain components. A series of simulation evaluations highlight the improved car-following stability and energy efficiency of the FCEV platoon.

Undenatured type II collagen protects against collagen-induced arthritis by restoring gut-joint homeostasis and immunity.

Oral administration of harmless antigens can induce suppression of reactive immune responses, a process that capitalises on the ability of the gastrointestinal tract to tolerate exposure to food and commensal microbiome without triggering inflammatory responses. Repeating exposure to type II collagen induces oral tolerance and inhibits induction of arthritis, a chronic inflammatory joint condition. Although some mechanisms underlying oral tolerance are described, how dysregulation of gut immune networks impacts on inflammation of distant tissues like the joints is unclear. We used undenatured type II collagen in a prophylactic regime -7.33 mg/kg three times/week- to describe the mechanisms associated with protective oral immune-therapy (OIT) in gut and joint during experimental Collagen-Induced Arthritis (CIA). OIT reduced disease incidence to 50%, with reduced expression of IL-17 and IL-22 in the joints of asymptomatic mice. Moreover, whilst the gut tissue of arthritic mice shows substantial damage and activation of tissue-specific immune networks, oral administration of undenatured type II collagen protects against gut pathology in all mice, symptomatic and asymptomatic, rewiring IL-17/IL-22 networks. Furthermore, gut fucosylation and microbiome composition were also modulated. These results corroborate the relevance of the gut-joint axis in arthritis, showing novel regulatory mechanisms linked to therapeutic OIT in joint disease.

Serum levels of vitamin B12 combined with folate and plasma total homocysteine predict ischemic stroke disease: a retrospective case-control study.

PURPOSE: This study aimed to identify and quantify the association and investigate whether serum vitamin B12 alone or vitamin B12 combined with folate and plasma total homocysteine (tHcy) levels could be used to predict the risk of acute ischemic stroke. MATERIALS AND METHODS: This retrospective case-control study was conducted in the Department of Neurology, First Affiliated Hospital of Chongqing Medical University. It included 259 inpatients experiencing their first-ever acute ischemic stroke and 259 age-matched, sex-matched healthy controls. Patients were categorized into groups based on the etiology of their stroke: large-artery atherosclerosis (LAAS, n = 126), cardio embolism (CEI, n = 35), small vessel disease (SVD, n = 89), stroke of other determined etiology (ODE, n = 5), and stroke of undetermined etiology (UDE, n = 4). The associations of serum vitamin B12, folate, and plasma tHcy levels with the risk of ischemic stroke were evaluated using multivariable logistic regression analysis. Receiver operator characteristic (ROC) curves were used to assess the diagnostic power of vitamin B12, folate, and tHcy levels for ischemic stroke. RESULTS: Serum vitamin B12 and folate levels were significantly lower in ischemic stroke patients compared to controls, while plasma tHcy levels were significantly higher. The first quartile of serum vitamin B12 levels was significantly associated with an increased risk of LAAS (aOR = 2.289, 95% CI = 1.098-4.770), SVD (aOR = 4.471, 95% CI = 1.110-4.945) and overall ischemic stroke (aOR = 3.216, 95% CI = 1.733-5.966). Similarly, the first quartile of serum folate levels was associated with an increased risk of LAAS (aOR = 3.480, 95% CI = 1.954-6.449), CEI (aOR = 2.809, 95% CI = 1.073-4.991), SVD (aOR = 5.376, 95% CI = 1.708-6.924), and overall ischemic stroke (aOR = 3.381, 95% CI = 1.535-7.449). The fourth quartile of tHcy levels was also significantly associated with an increased risk of LAAS (aOR = 2.946, 95% CI = 1.008-5.148), CEI (aOR = 2.212, 95% CI = 1.247-5.946), SVD (aOR = 2.957, 95% CI = 1.324-6.054), and overall ischemic stroke (aOR = 2.233, 95% CI = 1.586-4.592). For predicting different types of ischemic stroke, vitamin B12 alone demonstrated the best diagnostic value for SVD, evidenced by a sensitivity of 71.0% and negative predictive value of 90.3%, along with the highest positive likelihood ratio (+ LR) for SVD. Vitamin B12 + tHcy + folate are valuable in predicting different types of ischemic stroke, with the most significant effect observed in SVD, followed by LAAS, and the weakest predictive effect in CEI. Additionally, vitamin B12 alone in combination with other indicators, such as folate alone, tHcy alone, and folate + tHcy could reduce negative likelihood ratio (-LR) and improve + LR. CONCLUSIONS: Vitamin B12 was an independent risk factor for acute ischemic stroke. The risk calculation model constructed with vitamin B12 + tHcy + folate had the greatest diagnostic value for SVD.

The Loewner Energy via the Renormalised Energy of Moving Frames.

We obtain a new formula for the Loewner energy of Jordan curves on the sphere, which is a Kähler potential for the essentially unique Kähler metric on the Weil-Petersson universal Teichmüller space, as the renormalised energy of moving frames on the two domains of the sphere delimited by the given curve.

Growth mindset and well-being in social interactions: countering individual loneliness.

Introduction: Loneliness is a prevalent negative emotion experienced by college students. This study explores the relationship between a growth mindset and loneliness among college students. Methods: A total of 560 college students completed the Growth Mindset Scale (GMS), UCLA Loneliness Scale (UCLA), Interpersonal Relationships Assessment Scale (IRS), and two measures assessing distinct facets of well-being the Satisfaction with Life Scale (SWLS) and the revised Positive Affect and Negative Affect Scale (PANAS). Results and discussion: The results found a significant negative correlation between a growth mindset and loneliness. A growth mindset negatively predicted loneliness through the chain-mediated effects of interpersonal distress and well-being. These findings underscore the important role of a growth mindset in influencing loneliness, providing teachers and practitioners a new perspective to understand and intervene college students' psychological challenges.

Cuprate-like electronic structures in infinite-layer nickelates with substantial hole dopings.

Superconducting infinite-layer (IL) nickelates offer a new platform for investigating the long-standing problem of high-temperature superconductivity. Many models were proposed to understand the superconducting mechanism of nickelates based on the calculated electronic structure, and the multiple Fermi surfaces and multiple orbitals involved create complications and controversial conclusions. Over the past five years, the lack of direct measurements of the electronic structure has hindered the understanding of nickelate superconductors. Here we fill this gap by directly resolving the electronic structures of the parent compound LaNiO2 and superconducting La0.8Ca0.2NiO2 using angle-resolved photoemission spectroscopy. We find that their Fermi surfaces consist of a quasi-2D hole pocket and a 3D electron pocket at the Brillouin zone corner, whose volumes change upon Ca doping. The Fermi surface topology and band dispersion of the hole pocket closely resemble those observed in hole-doped cuprates. However, the cuprate-like band exhibits significantly higher hole doping in superconducting La0.8Ca0.2NiO2 compared to superconducting cuprates, highlighting the disparities in the electronic states of the superconducting phase. Our observations highlight the novel aspects of the IL nickelates, and pave the way toward the microscopic understanding of the IL nickelate family and its superconductivity.

Error Correction of the RapidEye Sub-Pixel Correlation: A Case Study of the 2019 Ridgecrest Earthquake Sequence.

The optical image sub-pixel correlation (SPC) technique is an important method for monitoring large-scale surface deformation. RapidEye images, distinguished by their short revisit period and high spatial resolution, are crucial data sources for monitoring surface deformation. However, few studies have comprehensively analyzed the error sources and correction methods of the deformation field obtained from RapidEye images. We used RapidEye images without surface deformation to analyze potential errors in the offset fields. We found that the errors in RapidEye offset fields primarily consist of decorrelation noise, orbit error, and attitude jitter distortions. To mitigate decorrelation noise, the careful selection of offset pairs coupled with spatial filtering is essential. Orbit error can be effectively mitigated by the polynomial fitting method. To address attitude jitter distortions, we introduced a linear fitting approach that incorporated the coherence of attitude jitter. To demonstrate the performance of the proposed methods, we utilized RapidEye images to extract the coseismic displacement field of the 2019 Ridgecrest earthquake sequence. The two-dimensional (2D) offset field contained deformation signals extracted from two earthquakes, with a maximum offset of 2.8 m in the E-W direction and 2.4 m in the N-S direction. A comparison with GNSS observations indicates that, after error correction, the mean relative precision of the offset field improved by 92% in the E-W direction and by 89% in the N-S direction. This robust enhancement underscores the effectiveness of the proposed error correction methods for RapidEye data. This study sheds light on large-scale surface deformation monitoring using RapidEye images.

[4D-DIA proteomics reveals mechanism of Sanpian Decoction in treating chronic migraine in rats].

To explore the mechanism of the classic formula Sanpian Decoction in treating chronic migraine, this study employed the four-dimensional data-dependent acquisition(4D-DIA) proteomics to analyze the effect of the decoction on chronic migraine in rats and experimentally verified the key differentially expressed proteins. Firstly, SD male rats were randomly divided into groups and repeatedly injected with nitroglycerin to prepare a chronic migraine model. After 7 consecutive days of gavage, rat grimace scale(RGS) was employed to evaluate the treatment efficacy. The trigeminal ganglion was collected for 4D-DIA proteomics, on the basis of which the diffe-rentially expressed proteins between groups were screened. Multiple databases were used for the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the differentially expressed proteins. STRING and Cytoscape were employed to establish the protein-protein interaction(PPI) network. Western blot was employed to determine the expression level of the key diffe-rentially expressed protein TRPV1. The results showed that there were 517 differentially expressed proteins between blank group and model group and 221 differentially expressed proteins between model group and medium-dose Sanpian Decoction group. The GO and KEGG enrichment results showed that these differentially expressed proteins were mainly related to inflammatory response, injurious sensory stimulation, triglyceride metabolism, immune regulation, etc., which mainly involved the inflammation-related TRP, AMPK, PI3K-Akt, and TGF-ß signaling pathways. The PPI network showed that the target proteins such as IGF, TOP2A, APOA1, CDK1, TTN, RYR1, and CSRP3 had high degrees. Compared with that in model group, the expression level of TRPV1 altered in medium-and high-dose Sanpian Decoction group(P<0.05). In conclusion, Sanpian Decoction may treat chronic migraine by regulating the inflammation-related pathways such as TRP, AMPK, and PI3K-Akt. It plays an important role in the regulation of TRPV1 protein and potentially modulates the perception of injurious stimuli, lipid metabolism, and immune responses.

Developing and Validating a Nomogram Model for Predicting Ischemic Stroke Risk.

Background and purpose: Clinically, the ability to identify individuals at risk of ischemic stroke remains limited. This study aimed to develop a nomogram model for predicting the risk of acute ischemic stroke. Methods: In this study, we conducted a retrospective analysis on patients who visited the Department of Neurology, collecting important information including clinical records, demographic characteristics, and complete hematological tests. Participants were randomly divided into training and internal validation sets in a 7:3 ratio. Based on their diagnosis, patients were categorized as having or not having ischemic stroke (ischemic and non-ischemic stroke groups). Subsequently, in the training set, key predictive variables were identified through multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods, and a nomogram model was constructed accordingly. The model was then evaluated on the internal validation set and an independent external validation set through area under the receiver operating characteristic curve (AUC-ROC) analysis, a Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis (DCA) to verify its predictive efficacy and clinical applicability. Results: Eight predictors were identified: age, smoking status, hypertension, diabetes, atrial fibrillation, stroke history, white blood cell count, and vitamin B12 levels. Based on these factors, a nomogram with high predictive accuracy was constructed. The model demonstrated good predictive performance, with an AUC-ROC of 0.760 (95% confidence interval [CI]: 0.736-0.784). The AUC-ROC values for internal and external validation were 0.768 (95% CI: 0.732-0.804) and 0.732 (95% CI: 0.688-0.777), respectively, proving the model's capability to predict the risk of ischemic stroke effectively. Calibration and DCA confirmed its clinical value. Conclusions: We constructed a nomogram based on eight variables, effectively quantifying the risk of ischemic stroke.

Discovery of a long-ranged charge order with 1/4 Ge1-dimerization in an antiferromagnetic Kagome metal.

Exotic quantum states arise from the interplay of various degrees of freedom such as charge, spin, orbital, and lattice. Recently, a short-ranged charge order (CO) was discovered deep inside the antiferromagnetic phase of Kagome magnet FeGe, exhibiting close relationships with magnetism. Despite extensive investigations, the CO mechanism remains controversial, mainly because the short-ranged behavior hinders precise identification of CO superstructure. Here, combining multiple experimental techniques, we report the observation of a long-ranged CO in high-quality FeGe samples, which is accompanied with a first-order structural transition. With these high-quality samples, the distorted 2 × 2 × 2 CO superstructure is characterized by a strong dimerization along the c-axis of 1/4 of Ge1-sites in Fe3Ge layers, and in response to that, the 2 × 2 in-plane charge modulations are induced. Moreover, we show that the previously reported short-ranged CO might be related to large occupational disorders at Ge1-site, which upsets the equilibrium of the CO state and the ideal 1 × 1 × 1 structure with very close energies, inducing nanoscale coexistence of these two phases. Our study provides important clues for further understanding the CO properties in FeGe and helps to identify the CO mechanism.