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Identifying neural biomarkers of pain has long been a central theme in pain neuroscience. Here, we review the state-of-the-art candidates for neural biomarkers of acute and chronic pain. We classify these potential neural biomarkers into five categories based on the nature of their target variables, including neural biomarkers of (1) within-individual perception, (2) between-individual sensitivity, and (3) discriminability for acute pain, as well as (4) assessment and (5) prospective neural biomarkers for chronic pain. For each category, we provide a synthesized review of candidate biomarkers developed using neuroimaging techniques including functional magnetic resonance imaging (fMRI), structural magnetic resonance imaging (sMRI), and electroencephalography (EEG). We also discuss the conceptual and practical challenges in developing neural biomarkers of pain. Addressing these challenges, optimal biomarkers of pain can be developed to deepen our understanding of how the brain represents pain and ultimately help alleviate patients' suffering and improve their well-being., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: 25-hydroxyvitamin D is the body's main storage form of vitamin D and is internationally recognized as the best indicator of vitamin D status in the human body. There is a scarcity of research investigating the interrelationship between serum 25-hydroxyvitamin D (25(OH)D) levels and mortality among elderly individuals with hyperlipidemia. To address this knowledge gap, we examined the association between serum 25(OH)D levels and mortality in an older hyperlipidemic population from NHANES, while controlling for other influential factors. The study sought to elucidate the correlation between serum 25(OH)D levels and mortality about all-cause mortality, cardiovascular disease (CVD), malignant neoplasms, and mortality from other causes., Methods: The data from NHANES 2001-2016, including 9,271 participants were analyzed to examine the association between serum 25(OH)D levels and mortality. The interrelationship was illustrated using Kaplan-Meier curves and restricted cubic splines, while the Cox proportional hazards model was utilized to estimate the multifactor adjusted hazard ratio (HR)., Results: This study included 9,271 participants (43.28% male) with an average age of 69.58 years, and the average duration of participant follow-up was 88.37 months. Kaplan-Meier curves demonstrated that lower serum 25(OH)D levels were associated with increased risks of all-cause mortality, cardiovascular mortality, malignant neoplasm mortality, and mortality from other causes. This negative association was further confirmed by the Cox proportional hazards models. Additionally, restricted cubic splines not only revealed this negative association but also highlighted the saturated serum 25(OH)D levels. Moreover, subgroup analyses indicated that the inverse correlation between serum 25(OH)D levels and all-cause mortality was more pronounced in the non-obese and smoking population. And the inverse correlation with mortality from other causes was even stronger in the non-obese population., Conclusions: In the elderly population with hyperlipidemia, 25(OH)D serum levels were negatively correlated with both cause-specific mortality and all-cause mortality. Moreover, there was a threshold effect in this negative association., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pan, Zhang, Sun, Shi and Zhang.)

Competing Interests: Declaration of interests We declare no competing interests.

Background: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials., Objective: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis., Methods: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale., Results: In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events., Conclusions: Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis., Clinical Trial Registration: ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021)., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Extracellular vesicles (EVs) are being considered as a potential therapeutic option for ulcerative colitis (UC), and numerous preclinical studies have been conducted on the use of EVs for UC., Methods: A systematic review was conducted to compare the therapeutic effects of mammalian EVs and placebo on UC in animal models, along with a meta-analysis comparing naïve (unmodified) EVs and placebo. The search was performed in four databases (PubMed, Web of Science, Scopus, and EMBASE) up to September 13th, 2023. The primary outcomes included disease activity index (DAI), colonic mucosal damage index (CMDI), and adverse effects (PROSPERO ID: CRD42023458039)., Results: A total of 69 studies were included based on pre-determined criteria, involving 1271 animals. Of these studies, 51 measured DAI scores, with 98 % reporting that EVs could reduce DAI scores. Additionally, 5 studies reported CMDI and all showed that EVs could significantly reduce CMDI. However, only 3 studies assessed adverse effects and none reported any significant adverse effects. The meta-analysis of these studies (40 studies involving 1065 animals) revealed that naïve EVs could significantly decrease the DAI score (SMD = -3.00; 95 % CI: -3.52 to -2.48) and CMDI (SMD = -2.10; 95 % CI: -2.85 to -1.35)., Conclusion: The results indicate that mammalian EVs have demonstrated therapeutic benefits in animal models of UC; however, the safety profile of EVs remains inadequate which highlights the need for further research on safety outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Backgrounds: Atrial fibrillation (AF) is a common complication of chronic heart failure (HF). Serum phenylalanine (Phe) levels are related to inflammation disorder. It is meaningful to study the circulating Phe with AF occurrence in HF., Methods: The cross-sectional study recruited 300 patients (78.0% male; mean age, 65 ± 13 years) with HF (left ventricular ejection fraction of ≤50%, containing 70 AF patients) and 100 normal controls. Serum Phe value was measured by liquid chromatography-tandem mass spectrometry. Logistic regression analysis was conducted to measure the association between Phe and AF risk in HF. The association between Phe and high-sensitivity C-reactive protein (hsCRP) was assessed by simple correlation analysis. In the prospective study, the 274 HF subjects (76.6% male; mean age, 65 ± 13 years) were followed up for a mean year (10.99 ± 3.00 months)., Results: Serum Phe levels increased across the control, the HF without AF, and the HF with AF groups (77.60 ± 8.67 umol/L vs. 95.24 ± 28.58 umol/L vs. 102.90 ± 30.43 umol/L, ANOVA P  < 0.001). Serum Phe value was the independent risk factor for predicting AF in HF [odds ratio (OR), 1.640; 95% CI: 1.150-2.339; P  = 0.006]. Phe levels were correlated positively with hsCRP value in HF patients with AF ( r  = 0.577, P  < 0.001). The elevated Phe levels were associated with a higher risk of HF endpoint events in HF patients with AF (log-rank P  = 0.005)., Conclusions: In HF with AF subjects, elevated Phe value confers an increased risk for prediction AF and was more related to poor HF endpoint events. Phe can be a valuable index of AF in HF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Zhou, Lu, Dai, Chen, He, Chen, Zhao, Zhang, Lu and Yang.)

This study aims to explore and analyze ancient proven prescriptions and famous physician cases for treating impotence, so as to obtain the core prescriptions for traditional Chinese medicine(TCM) treatment of impotence. It further selected and evaluated these core prescriptions to provide a demonstration for the development of new drugs for advantageous diseases treated with TCM. Through the retrieval of ancient proven prescriptions and famous physician cases for treating impotence, a database of prescriptions for treating impotence was established, and the TCM inheritance computational platform was used to explore and analyze the medication patterns of these proven prescriptions and famous physician cases. Based on the TCM efficacy prediction platform of network robustness, the interference scores of core prescriptions in the ancient proven prescriptions and famous physician cases were calculated and analyzed. On this basis, the results of ancient proven prescriptions, famous physician cases, and computational analysis were comprehensively evaluated to determine the development priority level of the core prescriptions obtained through clustering. The results revealed that medicines in the ancient proven prescriptions and famous physician cases primarily aimed at tonifying deficiency, promoting blood circulation, eliminating blood stasis, clearing heat, and resolving external symptoms, with a particular focus on warm-natured and sweet-flavored medicines associated with the spleen, liver, kidney, and lung meridians. The core prescriptions obtained from the clustering analysis of ancient proven prescriptions and famous physician cases indicated that ancient proven prescriptions combination 1 had the most perturbing effect on the disease network as determined by network robustness analysis. A comprehensive evaluation indicated that prescription combination 1 had the most optimal development potential. TCM treatment for impotence focused on regulating the functions of the spleen, liver, kidney, and lung, aiming to tonify deficiency, with heat-clearing, blood-activating, stasis-resolving, and exterior-releasing medications supplemented. The obtained ancient proven prescriptions combination 1 exhibited the highest potential development value. The integrated strategy of &quot;ancient proven prescriptions-famous physician cases-computational analysis&quot; can be utilized to screen candidate TCM new drug prescriptions.

Aims: We aim to explore the associations between serum tyrosine (Tyr) to threonine (Thr) ratio and chronic heart failure (HF) with reduced or mildly reduced ejection fraction (EF) (HFrEF or HFmrEF)., Methods and Results: The study recruited 418 subjects (77.5% males, mean age 65.2 ± 12.5 years), including 318 HF subjects (HFrEF or HFmrEF) and 100 cardiovascular subjects without acute or chronic HF [including heart failure with preserved ejection fraction (HFpEF)] as controls. Serum levels of 21 kinds of amino acids (AAs) were measured by mass spectrometry. Logistic regression analysis was conducted to measuring the association between the AAs levels and the presence of HF. Event-free survival was determined by Kaplan-Meier curves and differences in survival were assessed using log-rank tests. Cox regression analysis was used to assess the prognostic value of AAs in HF. Receiver-operating characteristic (ROC) curve was performed to further confirm regression analysis. Along with the control, HFmrEF, and HFrEF subjects, serum tyrosine (Tyr) gradually increased (64.43 ± 15.28 μmol/L vs. 71.79 ± 18.74 μmol/L vs. 77.32 ± 25.90 μmol/L, P < 0.001) while serum threonine (Thr) decreased (165.21 ± 40.09 μmol/L vs. 144.93 ± 44.56 μmol/L vs. 135.25 ± 41.25 μmol/L, P < 0.001). Tyr/Thr ratio was the independent risk factor for the presence of HF in all subjects [odds ratio (OR), 3.510; 95% confidence interval (CI): 2.445-5.040; P < 0.001]. After following up for a mean year (11.10 ± 2.80 months) in 269 HF subjects (75.1% males, mean age 65.2 ± 12.8 years), the higher Tyr/Thr ratio was associated with a higher risk of HF endpoint events in HF subjects [hazard ratio (HR), 2.901; 95% CI: 1.228-6.851; P = 0.015]. By comparing the area under the receiver-operating characteristic curve (AUC), Tyr/Thr ratio was superior to Fischer's ratio (FR) in predicting HF occurrence (0.767:0.573, P < 0.001) or cardiovascular (CV) death (0.715:0.550, P = 0.047)., Conclusions: Circulating elevated Tyr/Thr ratio confer an increased risk for the presence of HF and poor prognosis. Tyr/Thr index outweighs FR index in predicting HF occurrence or CV death., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The Angoumois grain moth, Sitotroga cerealella, is a destructive pest of maize, wheat, and rice, causing economic losses and threatening food security. This study aimed to develop and characterize microcapsules of mesoporous silica nanospheres (MSN) and cyclodextrin-modified mesoporous silica nanospheres (CDMSN) containing two aldehydes, nonanal and decanal, found in plant essential oils, to assess their attractiveness to S. cerealella populations., Results: Microcapsules with 2:1 ratio of nonanal and decanal exhibited an average encapsulation efficiency of 39.82% for MSN loaded with nonanal and decanal (MSN-ND) and 46.10% for CDMSN loaded with nonanal and decanal (CDMSN-ND). They have an elliptical shape with particle sizes of 115 nm for MSN and 175 nm for CDMSN. Gas chromatography-mass spectrometry analysis revealed in vitro release of nonanal in MSN at 96.24% and decanal at 96.42% by the 36th day. CDMSN showed releases of 93.83% for nonanal and 93.74% for decanal by the 50th day. CDMSN-ND attracted adult S. cerealella for 43 days, while MSN-ND remained effective for 29 days. In mass trapping assays in simulated grain warehouse, both MSN-ND and CDMSN-ND trapped over 50% of the adult population within 7 days, significantly reducing grain infestation rates below 10% by inhibiting F1 adult emergence. At temperatures ranging from 20 °C to 35 °C, both microcapsules exhibited significant and effective attraction rates for S. cerealella. Stored wheat seeds treated with CDMSN and CDMSN-ND over 1 year showed no significant differences in key germination parameters., Conclusion: Microencapsulated nonanal and decanal offer a promising, sustainable approach for controlling S. cerealella infestation in stored grains, contributing to global food security. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: The immune microenvironment assumes a significant role in the pathogenesis of osteoarthritis (OA). However, the current biomarkers for the diagnosis and treatment of OA are not satisfactory. Our study aims to identify new OA immune-related biomarkers to direct the prevention and treatment of OA using multi-omics data., Methods: The discovery dataset integrated the GSE89408 and GSE143514 datasets to identify biomarkers that were significantly associated with the OA immune microenvironment through multiple machine learning methods and weighted gene co-expression network analysis (WGCNA). The identified signature genes were confirmed using two independent validation datasets. We also performed a two-sample mendelian randomization (MR) study to generate causal relationships between biomarkers and OA using OA genome-wide association study (GWAS) summary data (cases n = 24,955, controls n = 378,169). Inverse-variance weighting (IVW) method was used as the main method of causal estimates. Sensitivity analyses were performed to assess the robustness and reliability of the IVW results., Results: Three signature genes (FCER1G, HLA-DMB, and HHLA-DPA1) associated with the OA immune microenvironment were identified as having good diagnostic performances, which can be used as biomarkers. MR results showed increased levels of FCER1G (OR = 1.118, 95% CI 1.031-1.212, P = 0.041), HLA-DMB (OR = 1.057, 95% CI 1.045 -1.069, P = 1.11E-21) and HLA-DPA1 (OR = 1.030, 95% CI 1.005-1.056, P = 0.017) were causally and positively associated with the risk of developing OA., Conclusion: The present study identified the 3 potential immune-related biomarkers for OA, providing new perspectives for the prevention and treatment of OA. The MR study provides genetic support for the causal effects of the 3 biomarkers with OA and may provide new insights into the molecular mechanisms leading to the development of OA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pang, Cai, Cao, Zhang, Zeng, Liu, Wang, Qu, Chen, Deng and Tan.)

This article designs and implements a fast and high-precision multi-robot environment modeling method based on bidirectional filtering and scene identification. To solve the problem of feature tracking failure caused by large angle rotation, a bidirectional filtering mechanism is introduced to improve the error-matching elimination algorithm. A global key frame database for multiple robots is proposed based on a pretraining dictionary to convert images into a bag of words vectors. The images captured by different sub-robots are compared with the database for similarity score calculation, so as to realize fast identification and search of similar scenes. The coordinate transformation from local map to global map and the cooperative SLAM exploration of multiple robots is completed by the best matching image and the transformation matrix. The experimental results show that the proposed algorithm can effectively close the predicted trajectory of the sub-robot, thus achieving high-precision collaborative environment modeling., Competing Interests: There are no conflicts of interest to disclose., (© 2024 The Authors.)

Previous studies reveal that psoriatic arthritis (PsA) and ankylosing spondylitis (AS) share susceptibility genes, such as HLA-B27, demonstrating a degree of genetic overlap between these diseases. Recent studies have identified a number of novel AS and PsA genetic susceptibility loci, but data on these loci in Chinese PsA patients are limited. To identify candidate genes that confer susceptibility to PsA in Chinese patients with PsA, psoriasis vulgaris (PsV), and healthy controls. Sixteen susceptibility loci, reported in a genome-wide association study of AS, and nine susceptibility loci, reported in candidate gene studies of PsA, were examined. Single-nucleotide polymorphisms (SNPs) were genotyped in 503 patients with PsA, 496 patients with PsV, and 979 healthy controls using the SNPscanTM multiplex SNP genotyping platform. PLINK software and logistic regression analysis were used to estimate the statistical significance of associations. PPP2R3C (rs8006884) was shown to significantly associate with PsA+PsV (p = 1.92×10-3, OR = 1.28) and was suggested to associate with PsV (p = 0.03, OR = 1.19). A suggestive association was also observed between IL-23R (rs12141575) and PsA as well as with axial PsA based on subtype analysis, KIF3A (rs2897442) and PsV, and ERN1 (rs196941) or IFIH1 (rs984971) and axial PsA. Our results suggest that PPP2R3C confers susceptibility to PsA and PsV, and that this gene may be related to the pathogenesis of psoriatic lesions and arthritis. Moreover, our results indicate a possible association between IL-23R, ERN1, or IFIH1 and subtypes of PsA, and between KIF3A and PsV.

Vascular dementia (VaD) represents a severe cognitive dysfunction syndrome closed linked to cardiovascular function. In the present study, we assessed the potential of Xinshubao tablet (XSB), a traditional Chinese prescription widely used for cardiovascular diseases, to mitigate neuropathological damage in a mouse model of VaD and elucidated the underlying mechanisms. Our findings revealed that oral administration of XSB rescued the cardiac dysfunction resulting from bilateral common carotid artery stenosis (BCAS), improved the cerebral blood flow (CBF) and cognitive function, reduced white matter injury, inhibited excessive microglial and astrocytic activation, stimulated hippocampal neurogenesis, and reduced neural apoptosis in the brains of BCAS mice. Mechanistically, RNA-seq analysis indicated that XSB treatment was significantly associated with neuroinflammation, vasculature development, and synaptic transmission, which were further confirmed by q-PCR assays. Western blot results revealed that XSB treatment hindered the nuclear translocation of nuclear factor-κB (NF-κB), thereby suppressing the NF-κB signaling pathway. These results collectively demonstrated that XSB could ameliorate cognitive dysfunction caused by BCAS through regulating CBF, reducing white matter lesions, suppressing glial activation, promoting neurogenesis, and mitigating neuroinflammation. Notably, the NF-κB signaling pathway emerged as a pivotal player in this mechanism., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Competing Interests: Declaration of interests We declare no competing interests.

Objective: To assess the utility of predictive models using ultrasound radiomic features to predict cervical lymph node metastasis (CLNM) in solitary papillary thyroid carcinoma (PTC) patients., Methods: A total of 570 PTC patients were included (456 patients in the training set and 114 in the testing set). Pyradiomics was employed to extract radiomic features from preoperative ultrasound images. After dimensionality reduction and meticulous selection, we developed radiomics models using various machine learning algorithms. Univariate and multivariate logistic regressions were conducted to identify independent risk factors for CLNM. We established clinical models using these risk factors. Finally, we integrated radiomic and clinical models to create a combined nomogram. We plotted ROC curves to assess diagnostic performance and used calibration curves to evaluate alignment between predicted and observed probabilities., Results: A total of 1561 radiomics features were extracted from preoperative ultrasound images. After dimensionality reduction and feature selection, 16 radiomics features were identified. Among radiomics models, the logistic regression (LR) model exhibited higher predictive efficiency. Univariate and multivariate logistic regression results revealed that patient age, tumor size, gender, suspicious cervical lymph node metastasis, and capsule contact were independent predictors of CLNM (all P < 0.05). By constructing a clinical model, the LR model demonstrated favorable diagnostic performance. The combined model showed superior diagnostic efficacy, with an AUC of 0.758 (95% CI: 0.712-0.803) in the training set and 0.759 (95% CI: 0.669-0.849) in the testing set. In the training dataset, the AUC value of the nomogram was higher than that of the clinical and radiomics models ( P = 0.027 and 0.002, respectively). In the testing dataset, the AUC value of the nomogram model was also greater than that of the radiomics models ( P = 0.012). However, there was no significant statistical difference between the nomogram and the clinical model ( P = 0.928). The calibration curve indicated a good fit of the combined model., Conclusion: Ultrasound radiomics technology offers a quantitative and objective method for predicting CLNM in PTC patients. Nonetheless, the clinical indicators persists as irreplaceable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Liu, Feng, Zheng, Xu, Zhang, Zhang and Feng.)

An in-depth study of the spatiotemporal variation characteristics and driving factors of ecosystem service values in the Liaohe River Delta is of great significance to its ecological environment governance and protection. Based on the land use data of the Liaohe River Delta for seven periods from 1990 to 2020, the ecosystem service value (ESV) was evaluated according to the equivalent factor coefficient correction method, establishing models for estimating the value of ecosystem services; the spatial and temporal evolution characteristics of the ESV in the study area were comprehensively analyzed; and the driving influencing factors and mechanisms of the ESV were explored. The results showed that:① From 1990 to 2020, the most common land use type in the Liaohe River Delta was cultivated land, and the areas of forest land, wetland, and unutilized land showed a decreasing trend; grassland, water, and construction land showed an increasing trend; and the area of cultivated land was basically unchanged during the 30 year period. ② In terms of the temporal evolution, the ESV in the study area showed a trend of first decreasing, then increasing, and then decreasing. In terms of the spatial distribution of ESV, the total value of ecosystem services as a whole showed a spatial divergence pattern of a high value in the southwest and low value in the northeast. ③ The sensitivity index of all land use types in the Liaohe River Delta was less than 1, indicating that the ESV was inelastic. ④ The value of ecosystem services in the Liaohe River Delta showed positive spatial coherence. On the whole, the Liaohe River Delta was dominated by HH and LL clusters, with HL clusters mostly distributed at the boundaries of LL clusters and LH clusters distributed at the boundaries of HH clusters. ⑤ Among the factors influencing the evolution of ESV in the Liaohe River Delta, DEM had the least influence, and HAI had the greatest influence on the ESV, followed by precipitation. The interaction results of all influencing factors had an enhancing effect on the spatial distribution of the ESV, among which HAI and precipitation had the strongest interaction effect, reaching 95.58%.