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Abstract Background Peer support is a promising and significant way for people living with HIV (PLWH) to improve their health outcomes. Matching PLWH with HIV peer volunteers can effectively stimulate and mobilize the function of peer support in health management. We develop the online platform Aspark, which features a precision matching function for PLWH and volunteers. This protocol provides a comprehensive overview of the randomized controlled trial design based on Aspark. Method A parallel randomized controlled trial using block randomization will be conducted at the Beijing YouAn Home of Loving Care. The intervention group (n = 70) will have access to all 12 features of Aspark, including precise volunteer matching, health management tools, drug interaction queries, and medication reminders. The control group (n = 70) will have access to two features of informational support on Aspark. The outcomes of both groups will be evaluated at baseline and at 3, 6, 9, and 12 months after platform registration. The primary outcome is perceived social support. The secondary outcomes include mental symptoms, quality of life, self-efficacy, medication adherence, and health behaviors. Linear mixed models or generalized linear mixed models will be applied to test the intervention effects. Discussion The Aspark trial is a randomized controlled trial designed to examine the influence of a mobile health (mHealth) application that integrates peer support and precision matching to strengthen social support for PLWH in China. This trial has the potential to significantly enhance social support for PLWH while also optimizing the delivery of peer support services and fully mobilizing the role of peer support in the overall health management of PLWH. Trial registration Clinical registration number: ChiCTR2300077454.

Abstract Peroxisomes are dynamic organelles involved in various cellular processes, including lipid metabolism, redox homeostasis, and intracellular metabolite transfer. Accumulating evidence suggests that peroxisomal homeostasis plays a crucial role in human health and disease, particularly in metabolic disorders and ferroptosis. The abundance and function of peroxisomes are regulated by a complex interplay between biogenesis and degradation pathways, involving peroxins, membrane proteins, and pexophagy. Peroxisome-dependent lipid metabolism, especially the synthesis of ether-linked phospholipids, has been implicated in modulating cellular susceptibility to ferroptosis, a newly discovered form of iron-dependent cell death. This review discusses the current understanding of peroxisome homeostasis, its roles in redox regulation and lipid metabolism, and its implications in human diseases. We also summarize the main mechanisms of ferroptosis and highlight recent discoveries on how peroxisome-dependent metabolism and signaling influence ferroptosis sensitivity. A better understanding of the interplay between peroxisomal homeostasis and ferroptosis may provide new insights into disease pathogenesis and reveal novel therapeutic strategies for peroxisome-related metabolic disorders and ferroptosis-associated diseases.

Abstract Sorghum is the world’s fifth-largest cereal crop, and anthracnose (Colletotrichum sublineola) is the main disease affecting sorghum. However, systematic research on the cellular structure, physiological and biochemical, and genes related to anthracnose resistance and disease resistance evaluation in sorghum is lacking in the field. Upon inoculation with anthracnose (C. sublineola) spores, disease-resistant sorghum (gz93) developed a relative lesion area (RLA) that was significantly smaller than that of the disease-susceptible sorghum (gz234). The leaf thickness, length and profile area of leaf mesophyll cells, upper and lower epidermal cells decreased in the lesion area, with a greater reduction observed in gz234 than in gz93. The damage caused by C. sublineola resulted in a greater decrease in the net photosynthetic rate (Pn) in gz234 than in gz93, with early-stage reduction due to stomatal limitation and late-stage reduction caused by lesions. Overall, the activities of superoxide dismutase (SOD) and catalase (CAT), the content of proline (Pro), abscisic acid (ABA), jasmonic acid (JA), salicylic acid (SA), and gibberellic acid (GA3), are higher in gz93 than in gz234 and may be positively correlated with disease resistance. While malondialdehyde (MDA) may be negatively correlated with disease resistance. Disease-resistant genes are significantly overexpressed in gz93, with significant expression changes in gz234, which is related to disease resistance in sorghum. Correlation analysis indicates that GA3, MDA, peroxidase (POD), and disease-resistance genes can serve as reference indicators for disease severity. The regression equation RLA = 0.029 + 8.02 × 10−6 JA–0.016 GA3 can predict and explain RLA. Principal component analysis (PCA), with the top 5 principal components for physiological and biochemical indicators and the top 2 principal components for disease-resistant genes, can explain 82.37% and 89.11% of their total variance, reducing the number of evaluation indicators. This study provides a basis for research on the mechanisms and breeding of sorghum with resistance to anthracnose.

Abstract Fueled by the rapid advancement of nanofabrication, metasurface has provided unprecedented opportunities for 3D holography. Large depth 3D meta-holography not only greatly increases information storage capacity, but also enables distinguishing of the relative spatial relationship of 3D objects, which has important applications in fields like optical information storage and medical diagnosis. Although the methods based on Fresnel diffraction theory can reconstruct the real depth information of 3D objects, the maximum depth is only 2 mm. Here, we develop a 3D meta-holography based on angular spectrum diffraction theory to break through the depth limit. By developing the angular spectrum diffraction theory into meta-holography, the metasurface structure with independent polarization control is used to create a polarization multiplexing 3D meta-hologram. The fabricated amorphous silicon metasurface increases the depth range by 47.5 times and realizes 0.95 dm depth reconstruction for polarization independent and different color 3D meta-hologram in visible. Such polarization controlled large-depth color meta-holography is expected to open avenue for data storage, display, information security and virtual reality.

Abstract Floquet engineering is a promising tool to manipulate quantum systems coherently. A well-known example is the optical Stark effect, which has been used for optical trapping of atoms and breaking time-reversal symmetry in solids. However, as a coherent nonlinear optical effect, Floquet engineering typically requires high field intensities obtained in ultrafast pulses, severely limiting its use. Here, we demonstrate using cavity engineering of the vacuum modes to achieve orders-of-magnitude enhancement of the effective Floquet field, enabling Floquet effects at an extremely low fluence of 450 photons/μm2. At higher fluences, the cavity-enhanced Floquet effects lead to 50 meV spin and valley splitting of WSe2 excitons, corresponding to an enormous time-reversal breaking, non-Maxwellian magnetic field of over 200 T. Utilizing such an optically controlled effective magnetic field, we demonstrate an ultrafast, picojoule chirality XOR gate. These results suggest that cavity-enhanced Floquet engineering may enable the creation of steady-state or quasi-equilibrium Floquet bands, strongly non-perturbative modifications of materials beyond the reach of other means, and application of Floquet engineering to a wide range of materials and applications.

Abstract Background Arginine vasopressin (AVP) has been reported to regulate insulin secretion and glucose homeostasis in the body. Previous study has shown that AVP and its receptor V1bR modulate insulin secretion via the hypothalamic-pituitary-adrenal axis. AVP has also been shown to enhance insulin secretion in islets, but the exact mechanism remains unclear. Results In our study, we unexpectedly discovered that AVP could only stimulates insulin secretion from islets, but not β cells, and AVP-induced insulin secretion could be blocked by V1bR selective antagonist. Single-cell transcriptome analysis identified that V1bR is only expressed by the α cells. Further studies indicated that activation of the V1bR stimulates the α cells to secrete glucagon, which then promotes glucose-dependent insulin secretion from β cells in a paracrine way by activating GLP-1R but not GCGR on these cells. Conclusions Our study revealed a crosstalk between α and β cells initiated by AVP/V1bR and mediated by glucagon/GLP-1R, providing a mechanism to develop new glucose-controlling therapies targeting V1bR.

Abstract Nutrition is a limiting feature of species evolution. The differences in nutritional requirements are the evolutionary result of differential adaptations to environmental changes, explaining differences in their ecological traits. Cnaphalocrocis medinalis and Cnaphalocrocis exigua, two related species of rice leaffolders, have similar morphology and feeding properties but different migration and overwintering behaviors. However, it is unclear whether they have evolved adult nutritional differentiation traits to coexist. To explore this issue, this study examined the effects of carbohydrates and amino acids on their reproductive and demographic parameters. The findings indicate that carbohydrate intake prolonged the longevity and population growth of two rice leaffolders, but amino acid intake promoted egg hatching only. However, nutrient deficiency made it impossible for C. medinalis to reproduce successfully and survive, but it did not affect C. exigua. The population expansion and survival of migratory C. medinalis relied on adult nutritional intake. Conversely, the nutrients necessary for C. exigua overwintering activity mostly came from the storage of larvae. The difference in nutritional requirements for population growth and survival between the two rice leaffolders partially explained their differences in migration and overwintering.

Abstract Background Diabetes-associated cognitive impairment (DACI) poses a significant challenge to the self-management of diabetes, markedly elevating the risk of adverse complications. A burgeoning body of evidence implicates microglia as a central player in the pathogenesis of DACI. Methods We utilized proteomics to identify potential biomarkers in high glucose (HG)-treated microglia, followed by gene knockdown techniques for mechanistic validation in vitro and in vivo. Results Our proteomic analysis identified a significant upregulation of AKAP8L in HG-treated microglia, with concurrent dysregulation of autophagy and inflammation markers, making AKAP8L a novel biomarker of interest. Notably, the accumulation of AKAP8L was specific to HG-treated microglia, with no observed changes in co-cultured astrocytes or neurons, a pattern that was mirrored in streptozotocin (STZ)-induced diabetic mice. Further studies through co-immunoprecipitation and proximity ligation assay indicated that the elevated AKAP8L in HG-treated microglial cells interacts with the mTORC1. In the STZ mouse model, we demonstrated that both AKAP8L knockdown and rapamycin treatment significantly enhanced cognitive function, as evidenced by improved performance in the Morris water maze, and reduced microglial activation. Moreover, these interventions effectively suppressed mTORC1 signaling, normalized autophagic flux, mitigated neuroinflammation, and decreased pyroptosis. Conclusions Our findings highlight the critical role of AKAP8L in the development of DACI. By interacting with mTORC1, AKAP8L appears to obstruct autophagic processes and initiate a cascade of neuroinflammatory responses. The identification of AKAP8L as a key mediator in DACI opens up new avenues for potential therapeutic interventions.

Abstract Background Brominated Flame Retardants (BFRs) have attracted widespread concern due to their environmental persistence and potential toxicity. This study aims to examine the association between BFRs exposure and hypertension. Methods We used data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2016 for the cross-sectional analysis. To evaluate the individual and combined impacts of BFRs exposure on hypertension, we utilized multivariate models, including generalized additive models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. Results 9882 individuals (48% male) aged ≥ 20 were included in the final analysis, of whom 4114 had hypertension. After controlling for potential covariates, higher serum concentrations of PBDE100 (OR: 1.26; 95% CI: 1.01, 1.57) and PBDE153 (OR: 1.50; 95% CI: 1.18, 1.88) were significantly associated with hypertension. A nonlinear relationship between PBDE28 and hypertension was observed (P = 0.03). Moreover, BFRs mixture were positively associated with the prevalence of hypertension in both the WQS (β:1.09; 95% CI: 1.02, 1.17; P = 0.02) and BKMR models. Conclusion Our study suggested that BFRs exposure is positively associated with hypertension in the general population. To confirm this association and elucidate the mechanisms, further research is required.

Abstract The neuropeptide 26RFa, a member of the RF-amide peptide family, activates the pyroglutamylated RF-amide peptide receptor (QRFPR), a class A GPCR. The 26RFa/QRFPR system plays critical roles in energy homeostasis, making QRFPR an attractive drug target for treating obesity, diabetes, and eating disorders. However, the lack of structural information has hindered our understanding of the peptide recognition and regulatory mechanism of QRFPR, impeding drug design efforts. In this study, we determined the cryo-EM structure of the Gq-coupled QRFPR bound to 26RFa. The structure reveals a unique assembly mode of the extracellular region of the receptor and the N-terminus of the peptide, and elucidates the recognition mechanism of the C-terminal heptapeptide of 26RFa by the transmembrane binding pocket of QRFPR. The study also clarifies the similarities and distinctions in the binding pattern of the RF-amide moiety in five RF-amide peptides and the RY-amide segment in neuropeptide Y. These findings deepen our understanding of the RF-amide peptide recognition, aiding in the rational design of drugs targeting QRFPR and other RF-amide peptide receptors.

Abstract Background Purple flowering stalk (Brassica rapa var. purpuraria) is a widely cultivated plant with high nutritional and medicinal value and exhibiting strong adaptability during growing. Mitochondrial (mt) play important role in plant cells for energy production, developing with an independent genetic system. Therefore, it is meaningful to assemble and annotate the functions for the mt genome of plants independently. Though there have been several reports referring the mt genome of in Brassica species, the genome of mt in B. rapa var. purpuraria and its functional gene variations when compared to its closely related species has not yet been addressed. Results The mt genome of B. rapa var. purpuraria was assembled through the Illumina and Nanopore sequencing platforms, which revealed a length of 219,775 bp with a typical circular structure. The base composition of the whole B. rapa var. purpuraria mt genome revealed A (27.45%), T (27.31%), C (22.91%), and G (22.32%). 59 functional genes, composing of 33 protein-coding genes (PCGs), 23 tRNA genes, and 3 rRNA genes, were annotated. The sequence repeats, codon usage, RNA editing, nucleotide diversity and gene transfer between the cp genome and mt genome were examined in the B. rapa var. purpuraria mt genome. Phylogenetic analysis show that B. rapa var. Purpuraria was closely related to B. rapa subsp. Oleifera and B. juncea. Ka/Ks analysis reflected that most of the PCGs in the B. rapa var. Purpuraria were negatively selected, illustrating that those mt genes were conserved during evolution. Conclusions The results of our findings provide valuable information on the B.rapa var. Purpuraria genome, which might facilitate molecular breeding, genetic variation and evolutionary researches for Brassica species in the future.

Cancer poses a substantial global health challenge, necessitating the widespread use of chemotherapy and radiotherapy. Despite these efforts, issues like resistance development and severe side effects remain. As such, the search for more effective alternatives is critical. Andrographolide, a naturally occurring compound, has recently gained attention for its extensive biological activities. This review explores the role of andrographolide in cancer therapy, especially focusing on the molecular mechanisms that drive its anti-tumor properties. It also examines innovative methods to enhance andrographolide's bioavailability, thus boosting its effectiveness against cancer. Notably, andrographolide has potential for use in combination with various clinical drugs, and both preclinical and clinical studies provide strong evidence supporting its broader anticancer applications. Additionally, this paper proposes future research directions for andrographolide's anti-cancer effects and discusses the challenges in its clinical usage along with current research efforts to address these issues. In summary, this review underscores andrographolide's potential roles and contributes to the development of improved cancer treatment strategies.

BackgroundThe gut microbiome has a significant impact on human wellness, contributing to the emergence and progression of a range of health issues including inflammatory and autoimmune conditions, metabolic disorders, cardiovascular problems, and psychiatric disorders. Notably, clinical observations have revealed that these illnesses can display differences in incidence and presentation between genders. The present study aimed to evaluate whether the composition of gut microbiota is associated with sex-specific differences and to elucidate the mechanism.Methods16S-rRNA-sequencing technology, hormone analysis, gut microbiota transplantation, gonadectomy, and hormone treatment were employed to investigate the correlation between the gut microbiome and sex or sex hormones. Meanwhile, genes and proteins involved bile acid signaling pathway were analyzed both in the liver and ileum tissues.ResultsThe composition and diversity of the microbiota from the jejunum and feces and the level of sex hormones in the serum differed between the sexes in young and middle-aged Sprague Dawley (SD) rats. However, no similar phenomenon was found in geriatric rats. Interestingly, whether in young, middle-aged, or old rats, the composition of the microbiota and bacterial diversity differed between the jejunum and feces in rats. Gut microbiota transplantation, gonadectomy, and hormone replacement also suggested that hormones, particularly testosterone (T), influenced the composition of the gut microbiota in rats. Meanwhile, the mRNA and protein level of genes involved bile acid signaling pathway (specifically SHP, FXR, CYP7A1, and ASBT) exhibited gender-specific differences, and T may play a significant role in mediating the expression of this pathway.ConclusionSex-specific differences in the structure of the gut microbiota are mediated by T through the bile acid signaling pathway, pointing to potential targets for disease prevention and management techniques by indicating that sex differences and T levels may alter the composition of the gut microbiota via the bile acid signaling pathway.

ObjectiveThis study aims to develop and validate SwinHS, a deep learning-based automatic segmentation model designed for precise hippocampus delineation in patients receiving hippocampus-protected whole-brain radiotherapy. By streamlining this process, we seek to significantly improve workflow efficiency for clinicians.MethodsA total of 100 three-dimensional T1-weighted MR images were collected, with 70 patients allocated for training and 30 for testing. Manual delineation of the hippocampus was performed according to RTOG0933 guidelines. The SwinHS model, which incorporates a 3D ELSA Transformer module and an sSE CNN decoder, was trained and tested on these datasets. To prove the effectiveness of SwinHS, this study compared the segmentation performance of SwinHS with that of V-Net, U-Net, ResNet and VIT. Evaluation metrics included the Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), and Hausdorff distance (HD). Dosimetric evaluation compared radiotherapy plans generated using automatic segmentation (plan AD) versus manual hippocampus segmentation (plan MD).ResultsSwinHS outperformed four advanced deep learning-based models, achieving an average DSC of 0.894, a JSC of 0.817, and an HD of 3.430 mm. Dosimetric evaluation revealed that both plan (AD) and plan (MD) met treatment plan constraints for the target volume (PTV). However, the hippocampal Dmax in plan (AD) was significantly greater than that in plan (MD), approaching the 17 Gy constraint limit. Nonetheless, there were no significant differences in D100% or maximum doses to other critical structures between the two plans.ConclusionCompared with manual delineation, SwinHS demonstrated superior segmentation performance and a significantly shorter delineation time. While plan (AD) met clinical requirements, caution should be exercised regarding hippocampal Dmax. SwinHS offers a promising tool to enhance workflow efficiency and facilitate hippocampal protection in radiotherapy planning for patients with brain metastases.

Rapid identification of peanut seed quality is crucial for public health. In this study, we present a terahertz wave imaging system using a convolutional neural network (CNN) machine learning approach. Terahertz waves are capable of penetrating the seed shell to identify the quality of peanuts without causing any damage to the seeds. The specificity of seed quality on terahertz wave images is investigated, and the image characteristics of five different qualities are summarized. Terahertz wave images are digitized and used for training and testing of convolutional neural networks, resulting in a high model accuracy of 98.7% in quality identification. The trained THz-CNNs system can accurately identify standard, mildewed, defective, dried and germinated seeds, with an average detection time of 2.2 s. This process does not require any sample preparation steps such as concentration or culture. Our method swiftly and accurately assesses shelled seed quality non-destructively.

Abstract The development and utilization of bulk resources provide the basic material needs for industrial systems. However, most current resource utilization patterns are unsustainable, with low efficiencies and high carbon emissions. Here, we report a quantitative tool for resource-based industries to facilitate sustainable and low-carbon transitions within the regional economy. To evaluate the effectiveness of this tool, the saline Qinghai Lake region was chosen as a case study. After optimizing the industrial structure, the benefits of economic output, resource efficiency, energy consumption, solid waste reduction, and carbon emission reduction can be obtained. The scenario analyses exhibit disparities in different transition paths, where the carbon mitigation, economic output, and resource efficiency that benefit from optimal development paths are significantly better than those of the traditional path, indicating the urgency of adopting cleaner technology and industrial symbiosis for regional industries.

Abstract Introduction Herpes zoster ophthalmicus (HZO) results from the reactivation of varicella zoster virus (VZV) in the ophthalmic branch of the trigeminal nerve. The inflammation caused by VZV involves multiple tissues in the eyes. Our goal is to evaluate pattern electroretinogram (PERG) changes and their relationship with corneal sub-basal nerve changes in patients with HZO. Methods Twenty-two patients with herpes zoster keratitis or conjunctivitis and 20 healthy volunteers were recruited for this cross-sectional study. A PERG test was performed on both eyes of HZO patients and one eye of the healthy controls. In vivo confocal microscopy (IVCM) was also performed on both eyes of the HZO patients to detect corneal nerve damage. Results Our results showed changes in the PERG parameters in both eyes of HZO patients compared to the healthy controls. Affected eyes showed delayed N95 peak time and decreased P50 and N95 amplitude compared to the unaffected eyes (p

Abstract Wind power prediction holds significant value for the stability of the electrical grid when wind power is connected to the grid. Using neural networks for wind power prediction may have some limitations, such as slow speed and low accuracy. This paper proposes to enhance the power prediction accuracy and speed by optimizing the neural network through health assessment wind turbines. Firstly, based on wind turbine actual operating data, a health assessment is conducted to obtain a health matrix of wind turbine. Then, by calculating the weights of the matrix, the power prediction strategy of the network is optimized. Following that, matrix approximation hyperparameters are utilized to expedite the optimization process. Finally, some tests are conducted on neural network power prediction, act as optimized back propagation (BP) neural network and whale swarm algorithm–support vector regression (WSA-SVR) neural networks are employed for wind power prediction. Results show noticeable optimization: after optimizing the BP network, power prediction accuracy increased by about 40%, and prediction speed rose by about 20%; after optimizing the WSA-SVR network, power prediction accuracy improved by 10%, and prediction speed surged by about 45%. Further analysis shows that this method can improve the accuracy and speed of most neural network wind power prediction algorithms.

Abstract The adenosine A3 receptor (A3AR), a key member of the G protein-coupled receptor family, is a promising therapeutic target for inflammatory and cancerous conditions. The selective A3AR agonists, CF101 and CF102, are clinically significant, yet their recognition mechanisms remained elusive. Here we report the cryogenic electron microscopy structures of the full-length human A3AR bound to CF101 and CF102 with heterotrimeric Gi protein in complex at 3.3-3.2 Å resolution. These agonists reside in the orthosteric pocket, forming conserved interactions via their adenine moieties, while their 3-iodobenzyl groups exhibit distinct orientations. Functional assays reveal the critical role of extracellular loop 3 in A3AR’s ligand selectivity and receptor activation. Key mutations, including His3.37, Ser5.42, and Ser6.52, in a unique sub-pocket of A3AR, significantly impact receptor activation. Comparative analysis with the inactive A2AAR structure highlights a conserved receptor activation mechanism. Our findings provide comprehensive insights into the molecular recognition and signaling of A3AR, paving the way for designing subtype-selective adenosine receptor ligands.

Abstract Proteins containing a ubiquitin regulatory X (UBX) domain are cofactors of Cell Division Cycle 48 (CDC48) and function in protein quality control. However, whether and how UBX-containing proteins participate in host–microbe interactions remain unclear. Here we show that MoNLE1, an effector from the fungal pathogen Magnaporthe oryzae, is a core virulence factor that suppresses rice immunity by specifically interfering with OsPUX8B.2. The UBX domain of OsPUX8B.2 is required for its binding to OsATG8 and OsCDC48-6 and controls its 26 S proteasome–dependent stability. OsPUX8B.2 and OsCDC48-6 positively regulate plant immunity against blast fungus, while the high-temperature tolerance heat-shock protein OsBHT, a putative cytoplasmic substrate of OsPUX8B.2–OsCDC48-6, negatively regulates defense against blast infection. MoNLE1 promotes the nuclear migration and degradation of OsPUX8B.2 and disturbs its association with OsBHT. Given the high conservation of MoNLE1 among fungal isolates, plants with broad and durable blast resistance might be generated by engineering intracellular proteins resistant to MoNLE1.

Abstract Objective Anesthetics have been linked to cognitive alterations, particularly in the elderly. The current research delineates how Fibroblast Growth Factor 2 (Fgf2) modulates tau protein phosphorylation, contributing to cognitive impairments in aged rats upon sevoflurane administration. Methods Rats aged 3, 12, and 18 months were subjected to a 2.5% sevoflurane exposure to form a neurotoxicity model. Cognitive performance was gauged, and the GEO database was employed to identify differentially expressed genes (DEGs) in the 18-month-old cohort post sevoflurane exposure. Bioinformatics tools, inclusive of STRING and GeneCards, facilitated detailed analysis. Experimental validations, both in vivo and in vitro, examined Fgf2’s effect on tau phosphorylation. Results Sevoflurane notably altered cognitive behavior in older rats. Out of 128 DEGs discerned, Fgf2 stood out as instrumental in regulating tau protein phosphorylation. Sevoflurane exposure spiked Fgf2 expression in cortical neurons, intensifying tau phosphorylation via the PI3K/AKT/Gsk3b trajectory. Diminishing Fgf2 expression correspondingly curtailed tau phosphorylation, neurofibrillary tangles, and enhanced cognitive capacities in aged rats. Conclusion Sevoflurane elicits a surge in Fgf2 expression in aging rats, directing tau protein phosphorylation through the PI3K/AKT/Gsk3b route, instigating cognitive aberrations.

ABSTRACTIn 2019, we conducted a cross-sectional study for polio virus seroprevalence in Guangdong province, China. We assessed the positivity rates of poliomyelitis NA and GMT in serum across various demographic groups, and the current findings were compared with pre-switch data from 2014. Using multistage random sampling method, four counties/districts were randomly selected per city, and within each, one general hospital and two township hospitals were chosen. Healthy individuals coming for medical checkups or vaccination were invited. A total of 1318 individual samples were collected and tested. In non-newborn population, age-dependent positivity rates ranged from 77.8% to 100% for PV1 NA and 70.3% to 98.9% for PV3 NA (p

Exosome-derived microRNAs (miRNAs) are biomacromolecules and nanoscale extracellular vesicles originating from intracellular compartments that are secreted by most cells into the extracellular space. This review examines the formation and function of exosomal miRNAs in biological information transfer, explores the pathogenesis of vitiligo, and highlights the relationship between exosomal miRNAs and vitiligo. The aim is to deepen the understanding of how exosomal miRNAs influence immune imbalance, oxidative stress damage, melanocyte-keratinocyte interactions, and melanogenesis disorders in the development of vitiligo. This enhanced understanding may contribute to the development of potential diagnostic and therapeutic options for vitiligo.

Abstract Background The peroxisome is a dynamic organelle with variety in number, size, shape, and activity in different cell types and physiological states. Recent studies have implicated peroxisomal homeostasis in ferroptosis susceptibility. Here, we developed a U-2OS cell line with a fluorescent peroxisomal tag and screened a target-selective chemical library through high-content imaging analysis. Methods U-2OS cells stably expressing the mOrange2-Peroxisomes2 tag were generated to screen a target-selective inhibitor library. The nuclear DNA was counterstained with Hoechst 33342 for cell cycle analysis. Cellular images were recorded and quantitatively analyzed through a high-content imaging platform. The effect of selected compounds on ferroptosis induction was analyzed in combination with ferroptosis inducers (RSL3 and erastin). Flow cytometry analysis was conducted to assess the level of reactive oxygen species (ROS) and cell death events. Results Through the quantification of DNA content and peroxisomal signals in single cells, we demonstrated that peroxisomal abundance was closely linked with cell cycle progression and that peroxisomal biogenesis mainly occurred in the G1/S phase. We further identified compounds that positively and negatively regulated peroxisomal abundance without significantly affecting the cell cycle distribution. Some compounds promoted peroxisomal signals by inducing oxidative stress, while others regulated peroxisomal abundance independent of redox status. Importantly, compounds with peroxisome-enhancing activity potentiated ferroptosis induction. Conclusions Our findings pinpoint novel cellular targets that might be involved in peroxisome homeostasis and indicate that compounds promoting peroxisomal abundance could be jointly applied with ferroptosis inducers to potentiate anticancer effect. Graphical Abstract

Miniaturized and lightweight Unmanned Aerial Vehicles (UAV) provide a flexible platform for Synthetic Aperture Radar (SAR). The application of UAV Interferometric SAR (InSAR) is gradually increasing in interferometric measurement fields. UAVs are small and light, which are easily affected by airflow disturbances. Their trajectories are nonlinear and unparallel when adopting the multipass mode for interferometry. The nonlinear and unparallel trajectories result in geometric distortion between the interferometric image pairs. Under complex topography conditions, the interferometric image pairs of UAVs have large offsets that are obviously space-dependent, thereby resulting in substantial technical challenges during image registration. Conventional image registration methods based on polynomial fitting are no longer applicable. In this study, we proposed an image registration method based on image partition with topography assistance. First, an elevation threshold is generated based on the UAV trajectories, and the measurement area is partitioned using the assisted topography. Then, a polynomial fitting model is constructed for offsets within each partition with constraints applied at the partition boundaries for joint optimization. Finally, continuous global offset fitting surfaces are obtained, and precise image registration is achieved by resampling the slave image. The effectiveness of the proposed method is preliminarily validated using real measurement data obtained from UAV InSAR in the P-band.

Ground-based arc-scanning synthetic aperture radar (GB-ArcSAR) can perform 360° scanning and has a large field of view. Based on the differential interferometry technique, GB-ArcSAR can be utilized to measure the surface deformation. However, affected by the rotating motion, rescanning angle error and rotation center offset during repeated scanning could occur. Through theoretical analysis, this article proves that the rescanning angle error has nearly no effect on the interferometric phase and can be negligible. The phase error caused by the rotation center offset can be built as a linear multiparameter model based on the multivariate Taylor expansion. Simulations are made to analyze the effect of the rotation center offset. A compensation method based on permanent scatterer technology is proposed, by using the least squares method, which jointly compensates the rotation center offset error and the atmospheric phase disturbance error. The compensation performance of the proposed method is validated in different scenarios, which can effectively improve the accuracy of deformation measurement.

Due to the specific arc-scanning way of ground-based arc-scanning synthetic aperture radar (GB-ArcSAR) to synthesize aperture, when a target's height is large enough and deviates much from the reference imaging plane, the image defocus would occur since that the target's range migration trajectory cannot be completely compensated. This article makes a theoretical analysis of the reasons for GB-ArcSAR imaging defocus, when it is utilized to observe those targets with large height differences, i.e., large elevation angles, from the imaging plane. A quantitative relationship between the imaging defocus level and the elevation angle is deduced with the simulation of an ideal target. Aiming at solving the problem of imaging defocus, an optimized imaging method of GB-ArcSAR based on the reference plane construction is proposed. A series of reference planes with different inclination angles or starting ranges are constructed and utilized for radar imaging separately. The minimum entropy criterion is then taken to search for the optimal plane. The qualitative and quantitative comparisons of the simulated and experimental datasets with other methods both prove the effectiveness of the proposed method.

Abstract Background Catheter ablation is recommended in patients with frequent and symptomatic ventricular arrhythmias (VAs) in an otherwise normal heart. Right or left outflow tract (OT) are the most common origins, and catheter ablation is highly effective with low complication rates. However, outcome of catheter ablation of VAs other than the OT (non-OTVAs) is limited. The aim of this single-center study was to assess the safety and mid-term outcome of catheter ablation for non-OTVAs. Method and Results From 2013 to 2018, 251 patients who underwent catheter ablation for idiopathic non-OTVAs were enrolled and grouped according to the origins including His-Purkinje system (HPS, n = 108), papillary muscle / moderator band (PM/MB, n = 47), tricuspid annulus (TA, n = 70), and mitral annulus (MA, n = 26), 244 (97.2%) had acute elimination of VAs. The time of VAs recurrence of the single procedure was 1.69 (0.12,9.72) months, with 66% occurring within the first 3 months. The recurrence rate was significantly higher in the PM/MB group than in the TA (p = 0.025) and MA groups (p = 0.023). The single procedure success rate in all patients was 70.1%, in which 66.7%, 59.6%, 80%, and 76.9% were achieved in the HPS, PM/MB, TA, and MA groups, respectively (p = 0.284). After multiple procedures, the total success rate was 76.5% at the follow-up of 4.38 ± 2.42 years. The rate was significantly lower in the PM/MB group than in the TA group (p = 0.035). In subgroup analysis, no significant difference was observed in the recurrence rate of single procedure in patients with different VA origins within the PM/MB (log-rank test, p = 0.546). Conclusion Despite a certain percentage of recurrences observed in the mid-term follow-up, catheter ablation remained feasible and effective for idiopathic non-OTVAs.

Abstract According to statistics, the incidence of liver cancer is increasing yearly, and effective treatment of liver cancer is imminent. For early liver cancer, resection surgery is currently the most effective treatment. However, resection does not treat the disease in advanced patients, so finding a method with a better prognosis is necessary. In recent years, ferroptosis and cuproptosis have been gradually defined, and related studies have proved that they show excellent results in the therapy of liver cancer. Cuproptosis is a new form of cell death, and the use of cuproptosis combined with ferroptosis to inhibit the production of hepatocellular carcinoma cells has good development prospects and is worthy of in-depth discussion by researchers. In this review, we summarize the research progress on cuproptosis combined with ferroptosis in treating liver cancer, analyze the value of cuproptosis and ferroptosis in the immune of liver cancer, and propose potential pathways in oncotherapy with the combination of cuproptosis and ferroptosis, which can provide background knowledge for subsequent related research.

Abstract Photothermal therapy (PTT) and photodynamic therapy (PDT) are effective method for tumor treatment. However, the limited variety and quantity of photothermal agents (PTAs) and photosensitizer (PSs) are still major challenges. Moreover, the cell apoptosis mechanism induced by PDT and PTT is still elusive. A fused-ring small molecule acceptor–donor acceptor′ donor–acceptor (A-DA′D-A) type of Y5 (Scheme 1) has a narrow band-gap and strong light absorption. Herein, we used Y5 to polymerize with thiophene unit to obtain polymer PYT based on polymerized small molecule strategy, and PYT nanoparticles (PYT NPs) was prepared via one-step nanoprecipitation strategy with DSPE-PEG2000. PYT NPs had excellent biocompatibility, good photostability, high photothermal conversion efficiency (67%) and reactive oxygen species (ROS) production capacity under 808 nm laser irradiation (PYT NPs + NIR). In vitro and in vivo experiments revealed that PYT NPs + NIR had the ability to completely ablate tumor cells. It was demonstrated that cell apoptosis induced by PYT NPs + NIR was closely related to mitochondrial damage. This study provides valuable guidance for constructing high-performance organic PTAs and PSs for tumor treatment. Scheme 1 PYT enabled by polymerized small molecule strategy for tumor photothermal and photodynamic therapy

Abstract Background This study aimed to systematically evaluate risk factors for post-operative recurrence after percutaneous endoscopic lumbar discectomy (PELD) in patients with lumbar disc herniation (LDH). Methods The eligible studies were retrieved from PubMed, Embase, and Web of Science databases. Quality assessment was performed. The effects of binary variables (sex, Modic change (MC), type 2 diabetes (T2DM), and smoking) on post-operative recurrence were evaluated as odds ratio (OR) and 95% confidence interval (CI). The effects of continuous variables (sagittal range of motion (SROM), body mass index (BMI), and age) were assessed as weighted mean difference (WMD) and 95% CI. Sensitivity analysis and publication bias were conducted to evaluate the reliability of pooled results. Results Eight studies were included, and their methodological quality was medium. MC (OR (95% CI) = 3.88 (2.24–6.74), P

As the largest non-gravitational force, solar radiation pressure (SRP) causes significant errors in precise orbit determination (POD) of the BeiDou global navigation satellite system (BDS-3) medium Earth orbit (MEO) satellite. This is mainly due to the imperfect modeling of the satellite’s cuboid body. Since the BDS-3’s inter-satellite link (ISL) can enhance the orbit estimation of BDS-3 satellites, the aim of this study is to establish an a priori SRP model for the satellite body using 281-day ISL observations to reduce the systematic errors in the final orbits. The adjustable box wind (ABW) model is employed to refine the optical parameters for the satellite buses. The self-shadow effect caused by the search and rescue (SAR) antenna is considered. Satellite laser ranging (SLR), day-boundary discontinuity (DBD), and overlapping Allan deviation (OADEV) are utilized as indicators to assess the performance of the a priori model. With the a priori model developed by both ISL and ground observation, the slopes of SLR residual for the China Academy of Space Technology (CAST) and Shanghai Engineering Center for Microsatellites (SECM) satellites decrease from −0.097 cm/deg and 0.067 cm/deg to −0.004 cm/deg and −0.009 cm/deg, respectively. The standard deviation decreased by 21.8% and 26.6%, respectively. There are slight enhancements in the average values of DBD and OADEV, and a reduced β-dependent variation is observed in the OADEV of the corresponding clock offset. We also found that considering the SAR antenna only slightly improves the orbit accuracy. These results demonstrate that an a priori model established for the BDS-3 MEO satellite body can reduce the systematic errors in orbits, and the parameters estimated using both ISL and ground observation are superior to those estimated using only ground observation.

Nonlinear disturbances, such as friction, backlash, and base vibration, are the main factors restricting the further improvement of the dynamic performance of the Acquisition, Tracking and Pointing (ATP) system. However, the modeling and compensation of the time-varying nonlinearities are still challenging. In this paper, a compound control algorithm based on model predictive control (MPC) and a Proportional Multiple-Integral State-Augmented Kalman Filter (PMISAKF) disturbance observer is proposed to improve the disturbance rejection performance. Specifically, a PMISAKF is used to estimate the system’s state and external disturbances in real-time. These observed disturbances are then treated as known external inputs at the current or future time points and incorporated into the predictive model of MPC. This allows the optimization process to take these external factors into consideration, enabling the calculation of an optimal control strategy and achieving high pointing and tracking accuracy for nonlinear time-varying disturbances. Experimental results show that the proposed method can effectively improve the system’s anti-interference ability and tracking accuracy.

Perceptual difficulty with an unfamiliar accent can dissipate within short time scales (e.g., within minutes), reflecting rapid adaptation effects. At the same time, long-term familiarity with an accent is also known to yield stable perceptual benefits. However, whether the long-term effects reflect sustained, cumulative progression from shorter-term adaptation remains unknown. To fill this gap, we developed a web-based, repeated exposure-test paradigm. In this paradigm, short test blocks alternate with exposure blocks, and this exposure-test sequence is repeated multiple times. This design allows for the testing of adaptive speech perception both (a) within the first moments of encountering an unfamiliar accent and (b) over longer time scales such as days and weeks. In addition, we used a Bayesian ideal observer approach to select natural speech stimuli that increase the statistical power to detect adaptation. The current report presents results from a first application of this paradigm, investigating changes in the recognition accuracy of Mandarin-accented speech by native English listeners over five sessions spanning 3 weeks. We found that the recognition of an accent feature (a syllable-final /d/, as in feed, sounding/t/-like) improved steadily over the three-week period. Unexpectedly, however, the improvement was seen with or without exposure to the accent. We discuss possible reasons for this result and implications for conducting future longitudinal studies with repeated exposure and testing.

BackgroundEmerging evidence links cellular senescence to the pathogenesis of major depressive disorder (MDD), a life-threatening and debilitating mental illness. However, the roles of cellular senescence-related genes in MDD are largely unknown and were investigated in this study using a comprehensive analysis.MethodsPeripheral blood microarray sequencing data were downloaded from Gene Expression Omnibus (GEO) database and retrieved cellular senescence-related genes from CellAge database. A weighted gene co-expression network analysis was used to screen MDD-associated genes. Protein-protein interactions (PPI) were predicted based on STRING data, and four topological algorithms were used to identify hub genes from the PPI network. Immune infiltration was evaluated using CIBERSORT, followed by a correlation analysis between hub genes and immune cells.ResultsA total of 84 cell senescence-related genes were differentially expressed in patients with MDD compared to healthy control participants. Among the 84 genes, 20 were identified to be associated with the MDD disease phenotype, and these genes were mainly involved in hormone-related signaling pathways (such as estrogen, steroid hormone, and corticosteroid) and immune and inflammatory pathways. Three genes, namely, JUN, CTSD, and CALR, which were downregulated in MDD, were identified as the hub genes. The expression of hub genes significantly moderate correlated with multiple immune cells, such as Tregs, NK cells, and CD4+ T cells, and the abundance of these immune cells markedly differed in MDD samples. Multiple microRNAs, transcription factors, and small-molecule drugs targeting hub genes were predicted to explore their molecular regulatory mechanisms and potential therapeutic value in MDD.ConclusionJUN, CTSD, and CALR were identified as potential diagnostic markers of MDD and may be involved in the immunoinflammatory mechanism of MDD.

Objectives: This study aims to investigate the use of sodium iodide (NaI), dimethyl sulfoxide (DMSO), ethyl alcohol, and ethyl acetate as cone-beam CT (CBCT) contrast agents for diagnosing cracked teeth. The optimal delay time for detecting the number of crack lines beyond the dentino-enamel junction (Nd), the number of cracks extending from the occlusal surface to the pulp cavity (Np), and the depth of the crack lines was explored. Methods: 14 human extracted cracked teeth were collected, 12 were used for enhanced scanning, and 2 were used for exploring the characteristic of crack lines. The teeth were scanned in 3 CBCT enhanced scanning (ES) modes: ES1 using meglumine diatrizoate (MD); ES2 using NaI and DMSO, ES3 using NaI, DMSO, ethyl alcohol and ethyl acetate. Three delay times (15mins, 30mins, and 60mins) were set for scanning. Nd, Np, and depth of crack lines were evaluated. Results: There were totally 24 crack lines on 12 cracked teeth. Nd was 10 in ES1 at 60mins, 24 in ES2 at 60mins and 24 in ES3 at 15mins. Np was 1 in ES1 at 60mins, 10 in ES2 at 60mins and 21 in ES3 at 60mins, and there were significantly different among them (p

BackgroundIn China, little is known about the hope level of older people living with HIV/AIDS (PLWHA).1 This study was to examine the hope level of older PLWHA in China and identify related factors.MethodsThis cross-sectional study was conducted in Sichuan province in China among older PLWHA.2 A standardized self-report questionnaire, the Herth Hope Index, was adopted. Multiple linear regression was used to identify factors influencing hope level. p-values

This quantitative study aimed to explore the relationships among music performance anxiety (MPA), teacher anxiety (TA), and self-efficacy (SE) through a survey study of Chinese preservice music teachers (N = 237). We also examined gender, grade, primary instrument, secondary instrument, music learning time length, and time spent in four activities: peer teaching, practicum, internship, and private teaching as potential predictors of MPA, TA, and SE. Results indicated that the higher the self-efficacy, the lower music performance anxiety and teaching anxiety; Simultaneously, the increased music performance anxiety was associated with an increased teaching anxiety. Partial correlation results indicated a significant but negative correlation between TA and SE with MPA controlled. Teaching anxiety, followed by primary piano, was the strongest predictor of MPA. MPA, followed by SE and peer teaching, was the strongest predictor of TA. TA, followed by grade level, was the strongest predictor of SE. The results from the multivariate analysis of variance revealed that the SE of male preservice music teachers were significantly higher than their female counterparts. As a study implication, music teacher educators may consider interventions and support mechanisms that address both types of anxiety simultaneously to improve overall teacher preparedness.

Objective: Deltamethrin (DLM) is a commonly used insecticide, which is harmful to many organs. Here, we explored the effects of chronic low-dose DLM residues on colon tissue and its potential mechanism. Methods: The mice were given long-term low-dose DLM by intragastric administration, and the body weights and disease activity index (DAI) scores of the mice were regularly recorded. The colon tissues were then collected for hematoxylin-eosin, immunofluorescence and immunohistochemistry staining. Besides, the RNA sequencing was performed to explore the potential mechanism. Results: Our results showed that long-term exposure to low-dose DLM could cause inflammation in mice colon tissue, manifested as weight loss, increased DAI score, increased apoptosis of colonic epithelial cells, and increased infiltration of inflammatory cells. However, we observed that after long-term exposure to DLM and withdrawal for a period of time, although apoptosis was restored, the recovery of colon inflammation was not ideal. Subsequently, we performed RNA sequencing and found that long-term DLM exposure could lead to the senescence of some cells in mice colon tissue. The results of staining of cellular senescence markers in colon tissue showed that the level of cellular senescence in the DLM group was significantly increased, and the p53 signalling related to senescence was also significantly activated, indicating that cellular senescence played a key role in DLM-induced colitis. We further treated mice with quercetin (QUE) after long-term DLM exposure, and found that QUE could indeed alleviate DLM-induced colitis. In addition, we observed that long-term accumulation of DLM could aggravate DSS-induced colitis in mice, and QUE treatment could reverse this scenario. Conclusion: Continuous intake of DLM caused chronic colitis in mice, and the inflammation persisted even after discontinuation of DLM intake. This was attributed to the induction of cellular senescence in colon tissue. Treatment with QUE alleviated DLM-induced colitis by reducing cellular senescence. Long-term DLM exposure also aggravated DSS-induced colitis, which could be mitigated by QUE treatment.

Aims: Dilated cardiomyopathy refers to a heart muscle condition characterized by structural and functional irregularities in the myocardium that are not related to ischemia. Due to diverse etiologies such as genetic mutations, infections, and exposure to toxins, dilated cardiomyopathy can lead to substantial morbidity and mortality despite advances in the management of heart failure in dilated cardiomyopathy patients. We sought to analyze the characteristics of cell-cell communication and the metabolic signaling pathways in dilated cardiomyopathy. Methods and results: The single-nucleus sequencing data of left ventricle samples were acquired from two donor datasets and two dilated cardiomyopathy datasets. Three dilated cardiomyopathy bulk-sequencing datasets were included to determine the shared dilated cardiomyopathy-specific alterations in differentially expressed genes and signaling pathways. Using “CellChat,” we analyzed intercellular communication to grasp how cell clusters interact and to map out the impaired signaling pathways in both donor and dilated cardiomyopathy conditions. Gene set enrichment analysis was applied to compare the metabolic signaling before and after dilated cardiomyopathy. We showcased how cell clusters exhibited abnormal cell-to-cell signaling transduction and how each cell type displayed dysfunctional metabolic signaling pathways through the integration of various datasets. The crucial ligand-receptor signaling contributing to outgoing or incoming signaling of dilated cardiomyopathy was identified in a cell-type dependent way, and the cell-specific metabolic alterations in glucose, lipid and amino acid were determined. The expression of gene pairs in BMP and NOTCH signal, as well as the gene expression in the arginine metabolism was validated. Conclusions: We reveal the key signals and metabolic pathways for dilated cardiomyopathy adaptation and maintenance, providing potential targets for dilated cardiomyopathy interference.

Abstract Imaging-guided photothermal therapy (PTT) for cancers recently gathered increasing focus thanks to its precise diagnosis and potent therapeutic effectiveness. Croconaine (CR) dyes demonstrate potential in expanding utility for near infrared (NIR) dyes in bio-imaging/theranostics. However, reports on CR dyes for PTT are scarce most likely due to the short of the efficacious delivery strategies to achieve specific accumulation in diseased tissues to induce PTT. Extracellular vesicles (EVs) are multifunctional nanoparticle systems that function as safe platform for disease theragnostics, which provide potential benefits in extensive biomedical applications. Here, we developed a novel delivery system for photothermal molecules based on a CR dye that exerts photothermal activity through CDH17 nanobody-engineered EVs. The formed CR@E8-EVs showed strong NIR absorption, excellent photothermal performance, good biological compatibility and superb active tumor-targeting capability. The CR@E8-EVs can not only visualize and feature the tumors through CR intrinsic property as a photoacoustic imaging (PAI) agent, but also effectively retard the tumor growth under laser irradiation to perform PTT. It is expected that the engineered EVs will become a novel delivery vehicle of small organic photothermal agents (SOPTAs) in future clinical PTT applications.

Abstract Background Accurate delineation of clinical target volume of tumor bed (CTV-TB) is important but it is also challenging due to surgical effects and soft tissue contrast. Recently a few auto-segmentation methods were developed to improve the process. However, those methods had comparatively low segmentation accuracy. In this study the prior information was introduced to aid auto-segmentation of CTV-TB based on a deep-learning model. Methods To aid the delineation of CTV-TB, the tumor contour on preoperative CT was transformed onto postoperative CT via deformable image registration. Both original and transformed tumor contours were used for prior information in training an auto-segmentation model. Then, the CTV-TB contour on postoperative CT was predicted by the model. 110 pairs of preoperative and postoperative CT images were used with a 5-fold cross-validation strategy. The predicted contour was compared with the clinically approved contour for accuracy evaluation using dice similarity coefficient (DSC) and Hausdorff distance. Results The average DSC of the deep-learning model with prior information was improved than the one without prior information (0.808 vs. 0.734, P

Abstract Microalgae as the photosynthetic organisms offer enormous promise in a variety of industries, such as the generation of high-value byproducts, biofuels, pharmaceuticals, environmental remediation, and others. With the rapid advancement of gene editing technology, CRISPR/Cas system has evolved into an effective tool that revolutionised the genetic engineering of microalgae due to its robustness, high target specificity, and programmability. However, due to the lack of robust delivery system, the efficacy of gene editing is significantly impaired, limiting its application in microalgae. Nanomaterials have become a potential delivery platform for CRISPR/Cas systems due to their advantages of precise targeting, high stability, safety, and improved immune system. Notably, algal-mediated nanoparticles (AMNPs), especially the microalgae-derived nanoparticles, are appealing as a sustainable delivery platform because of their biocompatibility and low toxicity in a homologous relationship. In addition, living microalgae demonstrated effective and regulated distribution into specified areas as the biohybrid microrobots. This review extensively summarised the uses of CRISPR/Cas systems in microalgae and the recent developments of nanoparticle-based CRISPR/Cas delivery systems. A systematic description of the properties and uses of AMNPs, microalgae-derived nanoparticles, and microalgae microrobots has also been discussed. Finally, this review highlights the challenges and future research directions for the development of gene-edited microalgae. Graphical Abstract

Abstract Background Arthroscopic technique procedures was wide accepted for the treatment of chronic ankle instability (CAI). But little acknowledge was involved to the bony landmarks and anatomic features of different bundles of lateral ligaments under arthroscopic view. Methods Sixty patients with acute or chronic lateral ankle ligaments injury (LAI) were collected prospectively, and divided randomly into two groups. In arthroscopic group, the bone tunnels were made on the LPF arthroscopically. And in open group, the bone tunnels were made on the Fibular obscure tubercle (FOT) in open procedure. The inferior bundle of ATFL and Arcuate fibre was also identified reference to the LPF and labeled by a PDS II suture penetration. Following that, The distances of the bone tunnels to the different bony markers were measured and compare between two groups. The penetrating locations of PDS II on the inferior bundle of ATFL and Arcuate fibre were also confirmed intraoperatively. And the safe angle of anchor implantation on the axial view was measured on postoperative CT scan. Results The distances of bone tunnel to the fibular tip, the fibular insertion of anterior-inferior tibiofibular ligament (AITFL), and the FOT in arthroscopic and open locating groups were 4.9 ± 2.2 and 6.3 ± 2.2 mm, 13.5 ± 2.7 and 12.4 ± 1.1 mm, 5.8 ± 2.2 and 5.6 ± 1.0 mm, respectively. The distances of bone tunnels to the FOT and fibular tip on 3d-CT view was 4.4 ± 1.5 and 4.6 ± 0.9 mm, 14.4 ± 3.2 and 13.2 ± 1.8 mm in arthroscopic and open group, and there were no significant differences between two groups. The safe angle of arthroscopic anchor placement on the axial plan was ranged from 24.9 ± 6.3o to 58.1 ± 8.0o. The PDS II sutures penetrating on the inferior bundles of ATFL and the arciform fibres were also comfirmed successfully by open visualizaion.The average distance of penetration point to the horizontal line cross the fibular tip was 2.3 ± 2.7 mm (ranged from − 3.1 to 6.0 mm), and to the vertical line cross the FOT was 2.7 ± 2.7 mm (ranged from − 2.5 to 7.5 mm). Conclusion Take the lowest point of fibula under arthroscopy (LPF) as a bony reference, we could identify the iATFL under arthroscopic visualization. By this way, we could place the suture anchors properly to the fibular footprint and suture the iATFL fibres successfully.

Abstract Macrophages are highly plastic in different tissues and can differentiate into functional subpopulations under different stimuli. Tumor-associated macrophages (TAMs) are one of the most important innate immune cells implicated in the establishment of an immunosuppressive tumor microenvironment (TME). Recent evidence pinpoints the critical role of metabolic reprogramming in dictating pro-tumorigenic functions of TAMs. Both tumor cells and macrophages undergo metabolic reprogramming to meet energy demands in the TME. Understanding the metabolic rewiring in TAMs can shed light on immune escape mechanisms and provide insights into repolarizing TAMs towards anti-tumorigenic function. Here, we discuss how metabolism impinges on the functional divergence of macrophages and its relevance to macrophage polarization in the TME.

Abstract Chemokines secreted by dendritic cells (DCs) play a key role in the regulation of inflammation and autoimmunity through chemokine receptors. However, the role of chemokine receptor CXCR1 in inflammation-inducing experimental autoimmune encephalomyelitis (EAE) and acute respiratory distress syndrome (ARDS) remains largely enigmatic. Here we reported that compared with healthy controls, the level of CXCR1 was aberrantly increased in multiple sclerosis (MS) patients. Knockout of CXCR1 not only ameliorated disease severity in EAE mice but also suppressed the secretion of inflammatory factors (IL-6/IL-12p70) production. We observed the same results in EAE mice with DCs-specific deletion of CXCR1 and antibody neutralization of the ligand CXCL5. Mechanically, we demonstrated a positive feedback loop composed of CXCL5/CXCR1/HIF-1α direct regulating of IL-6/IL-12p70 production in DCs. Meanwhile, we found CXCR1 deficiency in DCs limited IL-6/IL-12p70 production and lung injury in LPS-induced ARDS, a disease model caused by inflammation. Overall, our study reveals CXCR1 governs DCs-mediated inflammation and autoimmune disorders and its potential as a therapeutic target for related diseases.

Abstract Undruggable proteins are a class of proteins that are often characterized by large, complex structures or functions that are difficult to interfere with using conventional drug design strategies. Targeting such undruggable targets has been considered also a great opportunity for treatment of human diseases and has attracted substantial efforts in the field of medicine. Therefore, in this review, we focus on the recent development of drug discovery targeting “undruggable” proteins and their application in clinic. To make this review well organized, we discuss the design strategies targeting the undruggable proteins, including covalent regulation, allosteric inhibition, protein–protein/DNA interaction inhibition, targeted proteins regulation, nucleic acid-based approach, immunotherapy and others.

The complex influence of various disturbances on an inertially stabilized platform (ISP) restricts the further improvement of its servo performance. This article investigates the mapping relationship between internal and external disturbances and servo performance by establishing a high-precision dynamics model of the servo device with simulation and experiment. For internal disturbances, a nonlinear model of friction and backlash is established based on a BP neural network, and the transmission error is reconstructed based on the principle of main order invariance. For external disturbances, the road disturbance torque, changing inertia, and mass imbalance torque are modeled. The quantitative mapping relationship between internal and external disturbances and servo performance is obtained through simulation, in which friction and road disturbance are the largest internal and external factors affecting the servo performance, respectively. These conclusions are verified by load simulation experiments on a certain type of servo device, in which the servo performance is improved by 17% for every 25% reduction of friction torque, and the servo performance is reduced by 12% for every 33% increase of road disturbance torque. The research results provide a reference for servo device selection, performance indicator assignment, and performance prediction of the ISP.

The CRISPR-Cas9 system has emerged as the most prevalent gene editing technology due to its simplicity, high efficiency, and low cost. However, the homology-directed repair (HDR)-mediated gene knock-in in this system suffers from low efficiency, which limits its application in animal model preparation, gene therapy, and agricultural genetic improvement. Here, we report the design and optimization of a simple and efficient reporter-based assay to visualize and quantify HDR efficiency. Through random screening of a small molecule compound library, two groups of compounds, including the topoisomerase inhibitors and PIM1 kinase inhibitors, have been identified to promote HDR. Two representative compounds, etoposide and quercetagetin, also significantly enhance the efficiency of CRISPR-Cas9 and HDR-mediated gene knock-in in mouse embryos. Our study not only provides an assay to screen compounds that may facilitate HDR but also identifies useful tool compounds to facilitate the construction of genetically modified animal models with the CRISPR-Cas9 system.

Secondary cooling electromagnetic stirring (S-EMS) significantly impacts the internal quality of continuous casting slabs. In order to investigate the effects of S-EMS modes on segregation in slabs, a three-dimensional numerical model of the full-scale flow field, solidification, and mass transfer was established. A comparative analysis was conducted between continuous electromagnetic stirring and alternate stirring modes regarding their impacts on steel flow, solidification, and carbon segregation. The results indicated that adopting the alternate stirring mode was more advantageous for achieving uniform flow fields and reducing the disparity in solidification endpoints, thus mitigating carbon segregation. Specifically, the central carbon segregation index under continuous stirring at 320 A was 1.236, with an average of 1.247, while under alternate stirring, the central carbon segregation index decreased to 1.222 with an average of 1.227.