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Traditional Chinese medicine (TCM) prescription, with its intricate formulations and nuanced compositions, is a cornerstone of holistic health practices. However, the expansion of the TCM market has led to a surge in herb adulteration, which significantly undermines the quality and safety of these medicinal products. A case in point is Lonicerae Japonicae Flos (LJF), a widely utilized herb for treating colds, which has been adulterated by the cheaper Lonicerae Flos (LF), thereby affecting its therapeutic effectiveness. Therefore, a method utilizing handheld NIR spectroscopy combined with chemometrics has been developed to provide a portable, real-time solution for the rapid and accurate detection and quantification of adulterants in TCM. By collecting NIR spectra from LJF, LF and adulterated samples (AS), we've established a spectral database enabling deep insights into the correlation between spectral features and sample compositions. Resultantly, a classification model with a 99.58 % cross-validation accuracy, reaching 100 % for test set, effectively identified adulterants. And further spectral similarity analysis and classification identification of samples with different adulteration ratios were carried out. The cross-validation accuracy under the optimal model reached 98.38 %, and the test set accuracy was 99.20 %. In addition, the study extends to quantifying different levels of adulteration, employing 20 standard adulterated samples across a 0-100 % adulteration gradient. Via data preprocessing, feature extraction, and regression techniques, the full concentration prediction models were developed, later refined by segmenting samples based on high and low adulteration ratios. Under the SGFD_CARS_PLS (Savitzky-Golay smoothing with the first derivative_competitive adaptive reweighted sampling_partial least squares) model, exceptional performance was achieved, with a R2p of 0.983, RMSEp of 3.402, and RPDp of 7.757 for the homemade adulterated prediction set. In conclusion, the application of this technology not only improves the efficiency and accuracy of screening, but also has the advantages of low cost, easy operation and rapid results compared with traditional chemical analysis methods. It effectively protects the safety of drugs for consumers, maintains the integrity of the TCM market, and provides a strong technical support for the on-site rapid detection of TCM., Competing Interests: Declaration of competing interest 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., (Copyright © 2024. Published by Elsevier B.V.)

Background: Emotion recognition using electroencephalogram (EEG) has become a research hotspot in the field of human-computer interaction, how to sufficiently learn complex spatial-temporal representations of emotional EEG data and obtain explainable model prediction results are still great challenges., New Method: In this study, a novel hierarchical and explainable attention network ST-SHAP which combines the Swin Transformer (ST) and SHapley Additive exPlanations (SHAP) technique is proposed for automatic emotional EEG classification. Firstly, a 3D spatial-temporal feature of emotional EEG data is generated via frequency band filtering, temporal segmentation, spatial mapping, and interpolation to fully preserve important spatial-temporal-frequency characteristics. Secondly, a hierarchical attention network is devised to sufficiently learn an abstract spatial-temporal representation of emotional EEG and perform classification. Concretely, in this decoding model, the W-MSA module is used for modeling correlations within local windows, the SW-MSA module allows for information interactions between different local windows, and the patch merging module further facilitates local-to-global multiscale modeling. Finally, the SHAP method is utilized to discover important brain regions for emotion processing and improve the explainability of the Swin Transformer model., Results: Two benchmark datasets, namely SEED and DREAMER, are used for classification performance evaluation. In the subject-dependent experiments, for SEED dataset, ST-SHAP achieves an average accuracy of 97.18%, while for DREAMER dataset, the average accuracy is 96.06% and 95.98% on arousal and valence dimension respectively. In addition, important brain regions that conform to prior knowledge of neurophysiology are discovered via a data-driven approach for both datasets., Comparison With Existing Methods: In terms of subject-dependent and subject-independent emotional EEG decoding accuracies, our method outperforms several closely related existing methods., Conclusion: These experimental results fully prove the effectiveness and superiority of our proposed algorithm., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The pursuit of cutting-edge diagnostic systems capable of detecting biomarkers with exceptional sensitivity and precision is crucial for the timely and accurate monitoring of inflammatory responses. In this study, we introduce a dual gold nanoparticle-enhanced metasurface plasmon resonance (Bi-MSPR) biosensor for the ultrasensitive detection of C-reactive protein (CRP). The Bi-MSPR sensor is constructed upon a nanocup array chip with gradient-free electron density, where an innovative metasurface structure is built using a PEI-immobilized dual-gold nanoparticle amplification system. This strategy greatly amplifies the local free electric field, resulting in a signal enhancement exceeding 10-fold, with a detection limit of 0.04 ng/mL for CRP in buffer solutions and 0.017 μg/mL for serum samples. Clinical validation demonstrates a 95.83% detection rate with no cross-reactivity, highlighting the sensor's remarkable specificity and sensitivity for CRP detection. The Bi-MSPR biosensor thus represents a rapid, sensitive, and specific diagnostic tool for CRP detection.

Combined chemo-phototherapy has shown considerable advantages and potential in cancer treatment. For this purpose, self-assembled nanoparticles by gambogic acid (GA) and IR780 (referred to as GA-IR780 NPs) were prepared. Herein, GA, an active compound derived from Garcinia hanburyi Hook.f, was selected as a chemo-agent. IR780 was used as a photothermal agent as well as a photosensitizer, which could kill tumor cells via photothermal effect and photodynamic effect. The obtained GA-IR780 NPs were uniform spheres with particle size of ca. 50 nm. The drug loading efficiency of GA and IR780 was 38.42 % and 56.64 %, respectively. The GA-IR780 NPs exhibited excellent photothermal properties as well as photodynamic effect when irradiated by near infrared (NIR) light (808 nm, 2.0 W/cm 2 ). Moreover, the GA-IR780 NPs showed enhanced cytotoxicity with NIR light activation. Results of animal experiments showed that GA-IR780 NPs had the most significant tumor inhibition when irradiated by laser, and the results of H&E, Ki-67 and TUNEL staining confirmed that the GA-IR780 NPs+Laser group caused the most severe tumor tissue damage. The above results indicated that GA-mediated chemotherapy combining with IR780-based phototherapy could significantly improve the anti-tumor efficacy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kai Wu reports was provided by National Natural Science Foundation of China (No. 82204632). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To develop a deep learning system for automatic segmentation of compression fracture vertebral bodies on thoracolumbar CT and differentiate between fresh and old fractures., Methods: We included patients with thoracolumbar fractures treated at our Hospital South Campus from January 2020 to December 2023, with prospective validation from January to June 2024, and used data from the North Campus from January to December 2023 for external validation. Fresh fractures were defined as back pain lasting less than 4 weeks, with MRI showing bone marrow edema (BME). We utilized a 3D V-Net for image segmentation and several ResNet and DenseNet models for classification, evaluating performance with ROC curves, accuracy, sensitivity, specificity, precision, F1 score, and AUC. The optimal model was selected to construct deep learning system and its diagnostic efficacy was compared with that of two clinicians., Results: The training dataset included 238 vertebras (man/women: 55/183; age: 72.11 ± 11.55), with 59 in internal validation (man/women: 13/46; age: 74.76 ± 8.96), 34 in external validation, and 48 in prospective validation. The 3D V-Net model achieved a DSC of 0.90 on the validation dataset. ResNet18 performed best among classification models, with an AUC of 0.96 in validation, 0.89 in external dataset, and 0.87 in prospective validation, surpassing the two clinicians in both external and prospective validations., Conclusion: The deep learning model can automatically and accurately segment the vertebral bodies with compression fractures and classify them as fresh or old fractures, thereby assisting clinicians in making clinical decisions., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: This retrospective research had been approved by the Ethics Committee of Sun Yat-sen Memorial Hospital (Ethical number SYSKY-2023-1234-01)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale and Objectives: The purpose of this study is to conduct a meta-analysis to evaluate the diagnostic performance of current radiomics models for diagnosing osteoporosis, as well as to assess the methodology and reporting quality of these radiomics studies., Methods: According to PRISMA guidelines, four databases including MEDLINE, Web of Science, Embase and the Cochrane Library were searched systematically to select relevant studies published before July 18, 2024. The articles that used radiomics models for diagnosing osteoporosis were considered eligible. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool and radiomics quality score (RQS) were used to assess the quality of included studies. The pooled diagnostic odds ratio (DOR), sensitivity, specificity, area under the summary receiver operator characteristic curve (AUC) were calculated to estimated diagnostic efficiency of pooled model., Results: A total of 25 studies were included, of which 24 provided usable data that were utilized for the meta-analysis, including 1553 patients with osteoporosis and 2200 patients without osteoporosis. The mean RQS score of included studies was 11.48 ± 4.92, with an adherence rate of 31.89%. The pooled DOR, sensitivity and specificity for model to diagnose osteoporosis were 81.72 (95% CI: 51.08 - 130.73), 0.90 (95% CI: 0.87-0.93) and 0.90 (95% CI: 0.87-0.93), respectively. The AUC was 0.96, indicating a high diagnostic capability. Subgroup analysis revealed that the use of different imaging modalities to construct radiomics models might be one source of heterogeneity. Radiomics models built using CT images and deep learning algorithms demonstrated higher diagnostic accuracy for osteoporosis., Conclusion: Radiomics models for the diagnosis of osteoporosis have high diagnostic efficacy. In the future, radiomics models for diagnosing osteoporosis will be an efficient instrument to assist clinical doctors in screening osteoporosis patients. However, relevant guidelines should be followed strictly to improve the quality of radiomics studies., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the feasibility of using the iodine concentration (IC) parameter and extracellular volume (ECV) fraction derived from dual-energy CT for distinguishing between type I and type II epithelial ovarian carcinoma (EOC)., Methods: This study retrospectively included 172 patients with EOC preoperatively underwent dual-energy CT scans. Patients were grouped as type I and type II EOC according to postoperatively pathologic results. Normalized IC (NIC, %) values from arterial-phase (AP), venous-phase (VP) and delay-phase (DP) were measured by two observers. ECV fraction (%) was calculated by DP-NIC and hematocrit. Intra-observer correlation coefficient (ICC) was used to assess the agreement between measurements made by two observers. The differences of imaging parameters between the two groups were compared. Logistic regression was used to select independent predictive factors and establish combined parameter. Receiver operating characteristic curve was used to analyze performance of all parameters., Results: The ICCs for all parameters exceeded 0.75. All parameters in type II EOC were all significantly higher than those in type I EOC (all P < 0.05). VP-NIC exhibited the highest Area under the curve (AUC) of 0.804, along with 80.39% sensitivity and 71.43% specificity. VP-NIC was identified as the independent factor. The sensitivity and specificity of ECV fraction were 78.43% and 71.43%, respectively. The combined parameter consisting of AP-NIC, VP-NIC, DP-NIC, and ECV fraction yielded an AUC of 0.823, with sensitivity of 76.47% and specificity of 77.14%. The sensitivity of the combined parameter was significantly higher than that of AP-NIC (P = 0.049)., Conclusion: It is valuable for dual-energy CT IC-based parameters and ECV fraction in preoperatively identifying type I and type II EOC., Critical Relevance Statement: Dual-energy CT-normalized iodine concentration and extracellular volume fraction achieved satisfactory discriminative efficacy, distinguishing between type I and type II epithelial ovarian carcinoma., Competing Interests: Declarations. Ethical approval: The studies involving human participants were reviewed and approved by Institutional Review Board, XXX. Written informed consent for participation of this retrospective study was waived. Consent for publication: All authors contributed to the writing of the manuscript and consented to publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Study Design: Retrospective study analysis., Objective: To explore association between degenerative spinal conditions and paraspinal sarcopenia in patients with severe degenerative lumbar spinal stenosis (DLSS)., Background: Paraspinal muscles plays an essential role in stabilizing the spine. Paraspinal sarcopenia is progressively recognized as a crucial parameter influencing clinical outcomes in the field of spine surgery. The association between degenerative spinal conditions and paraspinal sarcopenia in patients with severe DLSS has been rarely investigated., Materials and Methods: This study was conducted on consecutive patients who underwent posterior lumbar interbody fusion at L4/5 single-level for lumbar spinal stenosis between January 2019 and July 2023. The study assessed paraspinal sarcopenia based on the fatty infiltration and Goutallier classification systems (GCS) of multifidus muscle on preoperative magnetic resonance imaging. The study evaluated the association between demographic/radiographic factors and paraspinal sarcopenia in patients with DSLL. Ordinal logistic regression analysis was then performed to adjust for confounding., Results: A total of 129 patients were included, including 38 patients with mild paraspinal sarcopenia, 52 patients with moderate paraspinal sarcopenia, and 39 patients with severe paraspinal sarcopenia. Correlation analysis indicated that age (r=0.366, P<0.001), pelvic incidence (PI) (r=0.407, P<0.001), lumbar lordosis (LL) (r=0.362, P=0.023) were positively correlated with paraspinal sarcopenia, while weight (r=-0.422, P<0.001), cross-sectional area (CSA) of psoas (r=-0613, P<0.001), facet joint angle (FA) (r=-0.447, P=0.016), and The Hounsfield Unit values of L1-L4 (L1-4 HU) (r=0.298, P=0.005) were negatively correlated with paraspinal sarcopenia. Ordinal logistic regression showed that the Facet joint osteoarthritis (FJOA) (odds ratio=2.82, P=0.017), PI (odds ratio=1.15, P<0.001), age (odds ratio=1.14, =0.001), and female (odds ratio=5.26, P=0.04) were associated with paraspinal sarcopenia., Conclusions: Our study demonstrated FJOA, PI, age, and female were associated with paraspinal sarcopenia. The assessments of paraspinal muscles cross-sectional area were not associated with the severity of fatty infiltration., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Dihydrotestosterone-induced androgen receptor activation and nuclear translocation was identified as the key event in androgen alopecia, which led to dermal papilla cell damage and hair growth cycle arrest. Inhibiting androgen receptor activation or nuclear translocation thus represents a potential therapeutic strategy for reducing dermal papilla cell damage and treating androgen alopecia., Purpose: To evaluate the effects of obacunone androgen alopecia and explore the potential underlying mechanisms., Methods: The effects of obacunone on androgen receptor activation and changes in the properties of dermal papilla cells were investigated. Meanwhile, the effects of obacunone on transforming growth factor-β-induced hair follicle stem cell damage and on androgen alopecia mice induced by dihydrotestosterone were evaluated., Results: Obacunone can competitively bind to androgen receptors with dihydrotestosterone, thereby alleviating the androgen receptor dimerization and nuclear translocation. The negative effects of dihydrotestosterone on dermal papilla cell apoptosis, senescence, and cycle arrest were alleviated by obacunone. Obacunone also counteracted the proliferation and apoptosis of transforming growth factor-β-mediated hair follicle stem cells. In mice with androgen alopecia, treatment with obacunone promoted mice hair growth and inhibited TGF-β/smad signaling., Conclusion: Thus, inhibiting androgen receptor dimerization was found to be an effective strategy for alleviating androgen alopecia. Obacunone follows a novel mechanism and holds potential as a drug candidate for androgen alopecia through inhibition of the dimerization of the androgen receptor. This targeting strategy may provide a new avenue for the development of new drugs different from the existing therapeutic approaches., Competing Interests: Declaration of competing interest 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. 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., (Copyright © 2024. Published by Elsevier GmbH.)

Adipose tissue inflammation is now considered to be a key process underlying metabolic diseases in obese individuals. However, it remains unclear how adipose inflammation is initiated and maintained or the mechanism by which inflammation develops. We found that microRNA-802 ( Mir802 ) expression in adipose tissue is progressively increased with the development of dietary obesity in obese mice and humans. The increasing trend of Mir802 preceded the accumulation of macrophages. Adipose tissue-specific knockout of Mir802 lowered macrophage infiltration and ameliorated systemic insulin resistance. Conversely, the specific overexpression of Mir802 in adipose tissue aggravated adipose inflammation in mice fed a high-fat diet. Mechanistically, Mir802 activates noncanonical and canonical NF-κB pathways by targeting its negative regulator, TRAF3. Next, NF-κB orchestrated the expression of chemokines and SREBP1, leading to strong recruitment and M1-like polarization of macrophages. Our findings indicate that Mir802 endows adipose tissue with the ability to recruit and polarize macrophages, which underscores Mir802 as an innovative and attractive candidate for miRNA-based immune therapy for adipose inflammation., Competing Interests: YY, BH, YQ, DW, YJ, LS, QW, YP, YZ, YS, WH, ZC, LJ, FZ No competing interests declared, (© 2024, Yang, Huang, Qin et al.)

Extracellular matrix (ECM) metabolism disorders in the inflammatory microenvironment play a key role in the pathogenesis of intervertebral disc degeneration (IDD). Interleukin-32 (IL-32) has been reported to be involved in the progression of various inflammatory diseases; however, it remains unclear whether it participates in the matrix metabolism of nucleus pulposus (NP) cells. Therefore, this study aimed to investigate the mechanism of IL-32 on regulating the ECM metabolism in the inflammatory microenvironment. RNA-seq was used to identify aberrantly expressed genes in NP cells in the inflammatory microenvironment. Western blotting, real-time quantitative PCR, immunohistochemistry and immunofluorescence analysis were performed to measure the expression of IL-32 and metabolic markers in human NP tissues or NP cells treated with or without tumor necrosis factor-α (TNF-α). In vivo, an adeno-associated virus overexpressing IL-32 was injected into the caudal intervertebral discs of rats to assess its effect on IDD. Proteins interacting with IL-32 were identified via immunoprecipitation and mass spectrometry. Lentivirus overexpressing IL-32 or knocking down Fat atypical cadherin 4 (FAT4), yes-associated protein (YAP) inhibitor-Verteporfin (VP) were used to treat human NP cells, to explore the pathogenesis of IL-32. Hippo/YAP signaling activity was verified in human NP tissues. IL-32 expression was significantly upregulated in degenerative NP tissues, as indicated in the clinical samples. Furthermore, IL-32 was remarkably overexpressed in TNF-α-induced degenerative NP cells. IL-32 overexpression induced IDD progression in the rat model. Mechanistically, the elevation of IL-32 in the inflammatory microenvironment enhanced its interactions with FAT4 and mammalian sterile 20-like kinase1/2 (MST1/2) proteins, prompting MST1/2 phosphorylation, and activating the Hippo/YAP signaling pathway, causing matrix metabolism disorder in NP cells. Our results suggest that IL-32 mediates matrix metabolism disorders in NP cells in the inflammatory micro-environment via the FAT4/MST/YAP axis, providing a theoretical basis for the precise treatment of IDD., Competing Interests: Declaration of competing interest 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., (Copyright © 2024. Published by Elsevier B.V.)

The interplay between gut microbiota and host is crucial for maintaining host health. When this balance is broken, various diseases can arise, including colorectal cancer (CRC). However, the mechanism by which gut microbiota and host interactions mediate CRC development remains unclear. Here, we found that Gasdermin D (GSDMD), an inflammasome effector responsible for forming membrane pores to mediate cell pyroptosis, was upregulated in both human and mouse intestinal tumor samples. GSDMD deficiency significantly suppressed intestinal tumor development in Apc min/+ mice, a spontaneous CRC mouse model. Apc min/+ Gsdmd -/- mice exhibited reduced IL-1β release in the intestine, and the administration of recombinant mouse IL-1β partially restored intestinal tumor development in Apc min/+ Gsdmd -/- mice. Moreover, 16s rRNA sequencing showed a substantial increase in Lactobacillus abundance in the feces of Apc min/+ Gsdmd -/- mice compared to Apc min/+ mice. Concurrently, Kynurenine (Kyn), a metabolite derived from host tryptophan (Trp) metabolism, was significantly decreased in the feces of Apc min/+ Gsdmd -/- mice, as shown by metabolite analysis. Additionally, Kyn levels were inversely correlated with Lactobacillus abundance. Furthermore, the administration of exogenous Kyn also promoted intestinal tumor development in Apc min/+ Gsdmd -/- mice. Thus, GSDMD promotes spontaneous CRC development through increasing IL-1β release and Kyn production. Our data suggest an association between GSDMD, gut microbiota, the host Trp/Kyn pathway, and CRC development., (© 2024. The Author(s).)

Objectives: To systematically evaluate the efficacy and safety of enteral nutrition with ω-3 polyunsaturated fatty acid preparations or standard enteral nutrition preparations used in patients with gastric cancer during perioperative period, and to provide reference for clinical rational drug use., Methods: Pubmed, EMbase, The Cochrane Library, CNKI and Wanfang Medical databases were searched by computer to collect relevant literature. The search period was from the establishment of the database to August 1, 2024. Meta-analysis was performed using Revman5.4 software after two researchers independently screened literature, extracted data, and evaluated the risk of bias in included studies., Results: A total of 20 randomized controlled studies were included. The Meta results showed that there was no statistical difference in mortality between the enteral nutrition with ω-3 polyunsaturated fatty acid group and the control group (RR = 0.46, P = 0.17). However, the IEN group demonstrated superior advantages in reducing infection complications (RR = 0.81, P = 0.05) and wound infection (RR = 0.61, P = 0.04) among gastric cancer patients, as well as improving immune-related indicators (including IgG, IgA, IgM, CD4, and CD4/CD8), inflammation-related markers (including CRP, IL-1β, and IL-6), and nutritional indicators (including Total protein, Albumin, and Transferrin)., Conclusion: enteral nutrition with ω-3 polyunsaturated fatty acid preparation has advantages in the efficacy and safety of perioperative nutritional therapy in patients with gastric cancer, and can be used as a clinical choice. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies., 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 Fu, Hu, Chang and Duan.)

Purpose: This study aimed to quantify and evaluate morphology of intervertebral space between neighboring cervical units using radiographic imaging indices, to help spine surgeons when performing anterior cervical discectomy and fusion (ACDF) surgery on the Chinese population., Methods: The background and imaging parameters of the subjects were assessed. Cervical lateral radiographs were employed to measure the intervertebral height (IH), intervertebral height index (IHI), and segmental lordosis (SL). Endplate parameters measurements were conducted on sagittal T2-weighted magnetic resonance imaging (MRI), including endplate sagittal diameter (ESD), and endplate concavity depth (ECD). All individuals were divided into three age groups: individuals aged 20-35 were in group A, individuals aged 36-50 were in group B, and individuals aged over 50 were in group C. A comparison of the variables was conducted among the three groups. Additionally, these radiographic parameters were also compared between males and females., Results: A total of 102 individuals were included in this study. IH was greater at C6/7 than those at other segmental levels (p < 0.001). The largest SL values were found at C6/7, while the least were found at C3/4. The superior ESD (ESDs) and ECD (ECDs) of the intervertebral space were significantly greater than those of the inferior endplates (p < 0.05). The ESD and ECD values were the largest at C6/7, while the least at C3/4. Additionally, age and gender had an influence on several parameters. IH was significantly lower in group A compared to group B (p < 0.05) and group C (p < 0.05) from C3/4 level to C6/7 level. ECDs were lower in group A compared to group B (p < 0.05) and group C (p < 0.05) at each level. IH and ESD in males were generally significantly greater than those in females at all levels (p < 0.05)., Conclusion: The current study found that C6/7 had the greatest IH, SL, ESD, and ECD values in asymptomatic Chinese. SL gradually increased from C3/4 to C6/7 levels. IH and ECD were significantly associated with age. Males had greater IH and ESD values than females. These findings provide baseline information for planning for selection of anterior screws and intervertebral implants., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The oil derived from Psidium guajava seeds (TKSO) exhibits an abundance of diverse unsaturated fatty acids, notably oleic, linoleic, and α-linolenic acids, conferring substantial health advantages in addressing metabolic irregularities and human diseases. This research endeavor focused on elucidating the impacts of TKSO on colonic inflammatory responses and intestinal microbiota alterations in a murine model of colitis induced by dextran sulfate sodium (DSS), demonstrated that substantial supplementation with TKSO reduces the severity of colitis induced by DSS. Furthermore, TKSO effectively attenuated the abundance and expression of proinflammatory mediators while augmenting the expression of tight junction proteins in DSS-challenged mice. Beyond this, TKSO intervention modulated the intestinal microbial composition in DSS-induced colitis mice, specifically by enhancing the relative presence of Lactobacillus , Norank&#95;f&#95;Muribaculaceae , and Lachnospiraceae&#95;NK4A136&#95; group, while concurrently diminishing the abundance of Turicibacter . Additionally, an analysis of short-chain fatty acids (SCFAs) revealed noteworthy elevations in acetic, propionic, isobutyric, and butyric acids, and total SCFAs levels in TKSO-treated mice. In summary, these findings underscore the potential of TKSO to reduce the severity of colitis induced by DSS in mice through intricate modulation of the intestinal microbiota, metabolite profiles, and intestinal barrier repair, thereby presenting a promising avenue for the development of therapeutic strategies against intestinal inflammatory conditions.

The deformation law of pipelines crossing landslide areas is an important prerequisite for the scientific design of pipelines. Most current studies find it difficult to simulate the real stress and strain state of pipelines on site. This study conducted two centrifuge model tests to observe pipeline failure indicators (deformation, stress, strain) and slope failure indicators (crack width, soil pressure, landslide displacement) in response to changes in acceleration. The experimental findings align with the results obtained from numerical simulations. The findings indicate that slope failure with high moisture content is more serious. At a moisture content of 15%, the slope has a maximum displacement of 70 mm in close reach to the buried pipeline. The pipeline has a "bimodal distribution" of strain along its axial length. The largest amount of deformation occurs at a distance of L/4 from the center of the pipeline, and the deformation value is 9000 με. Moreover, the maximum deformation in the mid-span is 21 mm, which corresponds to the result accumulated from the numerical simulation. Thus, the pipeline needs to improve the disaster prevention capabilities at the mid-span and L/4 of the pipeline., (© 2024. The Author(s).)

Obesity has become one of the most serious chronic diseases threatening human health. Its onset and progression are closely related to the intestinal microbiota, as disruption of the intestinal flora promotes the production of endotoxins and induces an inflammatory response. This study aimed to investigate the variations in the physicochemical properties of various refined tea seed oils and their impact on intestinal microbiota disorders induced by a high-fat diet (HFD) through dietary intervention. In the present study, C57BL/6J mice on a HFD were randomly divided into three groups: HFD, T-TSO, and N-TSO. T-TSO and N-TSO mice were given traditionally refined and optimized tea seed oil for 12 weeks. The data revealed that tea seed oil obtained through degumming at 70 °C, deacidification at 50 °C, decolorization at 90 °C, and deodorization at 180 °C (at 0.06 MPa for 1 h) effectively removed impurities while minimizing the loss of active ingredients. Additionally, the optimized tea seed oil mitigated fat accumulation and inflammatory responses resulting from HFD, and reduced liver tissue damage in comparison to traditional refining methods. More importantly, N-TSO can serve as a dietary supplement to enhance the diversity and abundance of intestinal microbiota, increasing the presence of beneficial bacteria ( norank&#95;f&#95;&#95;Muribaculaceae , Lactobacillus , and Bacteroides ) while reducing pathogenic bacteria ( Alistipes and Mucispirillum ). Therefore, in HFD-induced obese C57BL/6J mice, N-TSO can better ameliorate obesity compared with a T-TSO diet, which is promising in alleviating HFD-induced intestinal microbiota disorders.

Background: Systemic lupus erythematosus (SLE) is an immune-mediated and multi-systemic disease which may affect the nervous system, causing neuropsychiatric SLE (NPSLE). Recent neuroimaging studies have examined brain functional alterations in SLE. However, discrepant findings were reported. This meta-analysis aims to identify consistent resting-state functional abnormalities in SLE., Methods: PubMed and Web of Science were searched to identify candidate resting-state functional MRI studies assessing SLE. A voxel-based meta-analysis was performed using the anisotropic effect-size version of the seed-based d mapping (AES-SDM). The abnormal intrinsic functional patterns extracted from SDM were mapped onto the brain functional network atlas to determine brain abnormalities at a network level., Results: Twelve studies evaluating fifteen datasets were included in this meta-analysis, comprising 572 SLE patients and 436 healthy controls (HCs). Compared with HCs, SLE patients showed increased brain activity in the bilateral hippocampus and right superior temporal gyrus, and decreased brain activity in the left superior frontal gyrus, left middle temporal gyrus, bilateral thalamus, left inferior frontal gyrus and right cerebellum. Mapping the abnormal patterns to the network atlas revealed the default mode network and the limbic system as core neural systems commonly affected in SLE., Limitations: The number of included studies is relatively small, with heterogeneous analytic methods and a risk of publication bias., Conclusions: Brain functional alterations in SLE are predominantly found in the default mode network and the limbic system. These findings uncovered a consistent pattern of resting-state functional network abnormalities in SLE which may serve as a potential objective neuroimaging biomarker., Competing Interests: Declaration of competing interest The authors have declared no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Peptidyl arginine deiminase 4 (PAD4) plays a pivotal role in infection and inflammatory diseases by facilitating the formation of neutrophil extracellular traps (NETs). However, the substrates of PAD4 and its exact role in inflammatory bowel disease (IBD) remain unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) and substrate citrullination mapping to decipher the role of PAD4 in intestinal inflammation associated with IBD. Our results demonstrated that PAD4 deficiency alleviated colonic inflammation and restored intestinal barrier function in a dextran sulfate sodium (DSS)-induced colitis mouse model. scRNA-seq analysis revealed significant alterations in intestinal cell populations, with reduced neutrophil numbers and changes in epithelial subsets upon PAD4 deletion. Gene expression analysis highlighted pathways related to inflammation and epithelial cell function. Furthermore, we found that neutrophil-derived extracellular vesicles (EVs) carrying PAD4 were secreted into intestinal epithelial cells (IECs). Within IECs, PAD4 citrullinates mitochondrial creatine kinase 1 (CKMT1) at the R242 site, leading to reduced CKMT1 protein stability via the autophagy pathway. This action compromises mitochondrial homeostasis, impairs intestinal barrier integrity, and induces IECs apoptosis. IEC-specific depletion of CKMT1 exacerbated intestinal inflammation and apoptosis in mice with colitis. Clinical analysis of IBD patients revealed elevated levels of PAD4, increased CKMT1 citrullination, and decreased CKMT1 expression. In summary, our findings highlight the crucial role of PAD4 in IBD, where it modulates IECs plasticity via CKMT1 citrullination, suggesting that PAD4 may be a potential therapeutic target for IBD., (© 2024. The Author(s), under exclusive licence to CSI and USTC.)

Purpose: Nearly all patients with hip fractures undergo surgical treatment. The use of different anesthesia techniques during surgery may influence the clinical outcomes. The optimal anesthetic technique for patients undergoing hip fracture surgery is still controversial. We performed this updated systematic review and meta-analysis to compare clinical outcomes of patients undergoing hip fracture surgery with different anesthesia techniques., Source: Articles published from 2000 to May 2023 were included from MEDLINE, Embase, Web of Science, and the Cochrane Library. We included randomized controlled trials and observational studies comparing general anesthesia (GA) with regional anesthesia (RA) for the outcomes of 30-day mortality, 90-day mortality, in-hospital mortality, perioperative complications, length of hospital stay, and length of surgery in patients undergoing hip fracture surgery. Subgroup analyses were performed for the outcomes based on study design (randomized controlled trials or observational studies). We used a random-effects model for all analyses., Principal Findings: In this meta-analysis, we included 12 randomized controlled trials. There was no difference in postoperative 30-day mortality between the two groups (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.44 to 1.74; I 2  = 0%). The incidence of intraoperative hypotension was lower in patients who received RA vs GA (OR, 0.52; 95% CI, 0.38 to 0.72; I 2  = 0%). No significant differences were observed in 90-day mortality, in-hospital mortality, postoperative delirium, pneumonia, myocardial infarction, venous thromboembolism, length of surgery, and length of hospital stay., Conclusion: In this updated systematic review and meta-analysis, RA did not reduce postoperative 30-day mortality in hip fracture surgery patients compared to GA. Fewer patients receiving RA had intraoperative hypotension than those receiving GA did. Apart from intraoperative hypotension, the data showed no differences in complications between the two anesthetic techniques., Study Registration: PROSPERO (CRD42023411854); registered 7 April 2023., (© 2024. Canadian Anesthesiologists' Society.)

Meloidogyne incognita is one of the most widely distributed plant-parasitic nematodes and causes severe economic losses annually. The parasite produces effector proteins that play essential roles in successful parasitism. Here, we identified one such effector named MiCE108, which is exclusively expressed within the nematode subventral esophageal gland cells and is upregulated in the early parasitic stage of M. incognita. A yeast signal sequence trap assay showed that MiCE108 contains a functional signal peptide for secretion. Virus-induced gene silencing of MiCE108 impaired the parasitism of M. incognita in Nicotiana benthamiana. The ectopic expression of MiCE108 in Arabidopsis suppressed the deposition of callose, the generation of reactive oxygen species, and the expression of marker genes for bacterial flagellin epitope flg22-triggered immunity, resulting in increased susceptibility to M. incognita, Botrytis cinerea, and Pseudomonas syringae pv. tomato (Pst) DC3000. The MiCE108 protein physically associates with the plant defense protease RD21A and promotes its degradation via the endosomal-dependent pathway, or 26S proteasome. Consistent with this, knockout of RD21A compromises the innate immunity of Arabidopsis and increases its susceptibility to a broad range of pathogens, including M. incognita, strongly indicating a role in defense against this nematode. Together, our data suggest that M. incognita deploys the effector MiCE108 to target Arabidopsis cysteine protease RD21A and affect its stability, thereby suppressing plant innate immunity and facilitating parasitism., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

With the large-scale construction of oil and gas pipelines, the safety issues of long-distance buried pipelines in the service and construction have become increasingly prominent. The complex geological and topographical conditions of the special zone will put forwards extremely high requirements on pipe trench laying backfill materials and construction technology. For example, pipelines are inevitable to cross the active fault, while the trench backfilled with soil has limitations in protecting them from failure under the active fault displacement caused by the earthquake. Therefore, it is necessary to study the pipe-soil interaction mechanism, determine the stress state of the pipeline and propose a new backfilling material that can protect the pipeline from failure. Foam concrete (FC) provides a new choice to backfill the buried pipeline trench due to its high-homogeneity, lightweight, controllable-strength, and self-compacting. To further determine the applicability of the FC, the pipe-FC interaction mechanism is studied. Then, a FE model of the FC-pipeline-soil interaction system is established by Abaqus to quantitatively analyze the applicability of the FC based on the experimental data of the mechanical performance of the FC. It proves that using FC as trench backfill material has a noticeable protective effect on the pipeline under the earthquake-induced displacement of the normal fault. Furthermore, FC has a better protective effect on the pipeline subjected to compressive than tensile. Therefore, the reference for applying FC in trench backfilling of pipelines crossing normal fault is provided., (© 2024. The Author(s).)

Background: Diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) provide more comprehensive and informative perspective on microstructural alterations of cerebral white matter (WM) than single-shell diffusion tensor imaging (DTI), especially in the detection of crossing fiber. However, studies on systemic lupus erythematosus patients without neuropsychiatric symptoms (non-NPSLE patients) using multi-shell diffusion imaging remain scarce., Methods: Totally 49 non-NPSLE patients and 41 age-, sex-, and education-matched healthy controls underwent multi-shell diffusion magnetic resonance imaging. Totally 10 diffusion metrics based on DKI (fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, mean kurtosis, axial kurtosis and radial kurtosis) and NODDI (neurite density index, orientation dispersion index and volume fraction of the isotropic diffusion compartment) were evaluated. Tract-based spatial statistics (TBSS) and atlas-based region-of-interest (ROI) analyses were performed to determine group differences in brain WM microstructure. The associations of multi-shell diffusion metrics with clinical indicators were determined for further investigation., Results: TBSS analysis revealed reduced FA, AD and RK and increased ODI in the WM of non-NPSLE patients (P < 0.05, family-wise error corrected), and ODI showed the best discriminative ability. Atlas-based ROI analysis found increased ODI values in anterior thalamic radiation (ATR), inferior frontal-occipital fasciculus (IFOF), forceps major (F&#95;major), forceps minor (F&#95;minor) and uncinate fasciculus (UF) in non-NPSLE patients, and the right ATR showed the best discriminative ability. ODI in the F&#95;major was positively correlated to C3., Conclusion: This study suggested that DKI and NODDI metrics can complementarily detect WM abnormalities in non-NPSLE patients and revealed ODI as a more sensitive and specific biomarker than DKI, guiding further understanding of the pathophysiological mechanism of normal-appearing WM injury in SLE., (© 2024. The Author(s).)

Intervertebral disc degeneration (IDD) is the cause of low back pain (LBP), and recent research has suggested that inflammatory cytokines play a significant role in this process. Maslinic acid (MA), a natural compound found in olive plants ( Olea europaea ), has anti-inflammatory properties, but its potential for treating IDD is unclear. The current study aims to investigate the effects of MA on TNFα-induced IDD in vitro and in other in vivo models. Our findings suggest that MA ameliorates the imbalance of the extracellular matrix (ECM) and mitigates senescence by upregulating aggrecan and collagen II levels as well as downregulating MMP and ADAMTS levels in nucleus pulposus cells (NPCs). It can also impede the progression of IDD in rats. We further find that MA significantly affects the PI3K/AKT and NF-κB pathways in TNFα-induced NPCs determined by RNA-seq and experimental verification, while the AKT agonist Sc-79 eliminates these signaling cascades. Furthermore, molecular docking simulation shows that MA directly binds to PI3K. Dysfunction of the PI3K/AKT pathway and ECM metabolism has also been confirmed in clinical specimens of degenerated nucleus pulposus. This study demonstrates that MA may hold promise as a therapeutic agent for alleviating ECM metabolism disorders and senescence to treat IDD.

Purpose: To develop and validate a nomogram based on extracellular volume (ECV) fraction derived from dual-energy CT (DECT) for preoperatively predicting microsatellite instability (MSI) status in gastric cancer (GC)., Materials and Methods: A total of 123 patients with GCs who underwent contrast-enhanced abdominal DECT scans were retrospectively enrolled. Patients were divided into MSI (n=41) and microsatellite stability (MSS, n=82) groups according to postoperative immunohistochemistry staining, then randomly assigned to the training (n=86) and validation cohorts (n=37). We extracted clinicopathological characteristics, CT imaging features, iodine concentrations (ICs), and normalized IC values against the aorta (nICs) in three enhanced phases. The ECV fraction derived from the iodine density map at the equilibrium phase was calculated. Univariate and multivariable logistic regression analyses were used to identify independent risk predictors for MSI status. Then, a nomogram was established, and its performance was evaluated by ROC analysis and Delong test. Its calibration performance and clinical utility were assessed by calibration curve and decision curve analysis, respectively., Results: The ECV fraction, tumor location, and Borrmann type were independent predictors of MSI status (all P < 0.05) and were used to establish the nomogram. The nomogram yielded higher AUCs of 0.826 (0.729-0.899) and 0.833 (0.675-0.935) in training and validation cohorts than single variables ( P <0.05), with good calibration and clinical utility., Conclusions: The nomogram based on DECT-derived ECV fraction has the potential as a noninvasive biomarker to predict MSI status in GC patients., 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 Hu, Zhao, Ji, Chen, Xu, Liu, Zhang and Liu.)

Objectives: This study aimed to evaluate the activity of the glymphatic system in systemic lupus erythematosus (SLE) by a diffusion-based method termed "Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS)", and examined its correlations with morphological changes in the brain., Methods: In this cross-sectional study, forty-five female patients with SLE and thirty healthy controls (HCs) were included. Voxel-based and surface-based morphometric analyses were performed to examine T1 weighted images, and diffusion tensor images were acquired to determine diffusivity along the x-, y-, and z-axes in the plane of the lateral ventricle body. The ALPS-index was calculated. The differences in values between SLE patients and HC group were compared using the independent samples t test or Mann-Whitney U test. For the correlations between the ALPS-index and brain morphological parameters, partial correlation analysis and Pearson's correlation analysis were conducted., Results: SLE patients showed lower values for the ALPS-index in left (1.543 ± 0.141 vs 1.713 ± 0.175, p < 0.001), right (1.428 ± 0.142 vs 1.556 ± 0.139, p < 0.001) and whole (1.486 ± 0.121 vs 1.635 ± 0.139, p < 0.001) brain compared with the HC group. The reduced ALPS-index showed significant positive correlations with gray matter loss., Conclusion: The non-invasive ALPS-index could serve as a sensitive and effective neuroimaging biomarker for individually quantifying glymphatic activity in patients with SLE. Glymphatic system abnormality may be involved in the pathophysiologic mechanism underlying central nervous system damage in SLE patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Cyclophosphamide (Cy) is a frequently used chemotherapeutic drug, but long-term Cy treatment can cause immunosuppression and intestinal mucosal damage. The intestinal mucosal barrier and gut flora play important roles in regulating host metabolism, maintaining physiological functions and protecting immune homeostasis. Dysbiosis of the intestinal flora affects the development of the intestinal microenvironment, as well as the development of various external systemic diseases and metabolic syndrome., Results: The present study investigated the influence of sciadonic acid (SA) on Cy-induced immunosuppression in mice. The results showed that SA gavage significantly alleviated Cy-induced immune damage by improving the immune system organ index, immune response and oxidative stress. Moreover, SA restored intestinal morphology, improved villus integrity and activated the nuclear factor κB signaling pathway, stimulated cytokine production, and reduced serum lipopolysaccharide (LPS) levels. Furthermore, gut microbiota analysis indicated that SA increased t beneficial bacteria (Alistipes, Lachnospiraceae&#95;NK4A136&#95;group, Rikenella and Odoribacter) and decreased pathogenic bacteria (norank-f-Oscillospiraceae, Ruminococcus and Desulfovibrio) to maintain intestinal homeostasis., Conclusion: The present study provided new insights into the SA regulation of intestinal flora to enhance immune responses. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

In the face of escalating metabolic disease prevalence, largely driven by modern lifestyle factors, this study addresses the critical need for novel therapeutic approaches. We have identified the sodium-coupled citrate transporter (NaCT or SLC13A5) as a target for intervention. Utilizing rational drug design, we developed a new class of SLC13A5 inhibitors, anchored by the hydroxysuccinic acid scaffold, refining the structure of PF-06649298 . Among these, LBA-3 emerged as a standout compound, exhibiting remarkable potency with an IC 50 value of 67 nM, significantly improving upon PF-06649298 . In vitro assays demonstrated LBA-3 's efficacy in reducing triglyceride levels in OPA-induced HepG2 cells. Moreover, LBA-3 displayed superior pharmacokinetic properties and effectively lowered triglyceride and total cholesterol levels in diverse mouse models (PCN-stimulated and starvation-induced), without detectable toxicity. These findings not only spotlight LBA-3 as a promising candidate for hyperlipidemia treatment but also exemplify the potential of targeted molecular design in advancing metabolic disorder therapeutics.

High-fat diet (HFD) has been associated with certain negative bone-related outcomes, such as bone metabolism disruption and bone loss. Sciadonic acid (SC), one of the main nutritional and functional components of Torreya grandis seed oil, is a unique Δ5-unsaturated-polymethylene-interrupted fatty acid (Δ5-UPIFA) that has been claimed to counteract such disorders owing to some of its physiological effects. However, the role of SC in ameliorating bone metabolism disorders due to HFD remains unclear. In the present investigation, we observed that SC modulates the OPG/RANKL/RANK signaling pathway by modifying the lipid metabolic state and decreasing inflammation in mice. In turn, it could balance bone resorption and formation as well as calcium and phosphorus levels, enhance bone strength and bone mineral density (BMD), and improve its microstructure. In addition, SC could inhibit fat vacuoles in bone, reverse the phenomenon of reduced numbers and poor continuity of bone trabeculae, and promote orderly arrangement of collagen fibers and cartilage repair. This study provides some theoretical basis for SC as a dietary intervention agent to enhance bone nutrition.

The accumulation of trace amounts of certain small molecules in food poses considerable human health challenges, including the potential for carcinogenesis and mutagenesis. Here, an ultrasensitive gold-platinum nanoflower-coupled metasurface plasmon resonance (MetaSPR) (APNMSPR) biosensor, based on a competitive immunoassay, was developed for the multiplexed and rapid quantitative analysis of trace small molecules in eggs, offering timely monitoring of food safety. This one-step biosensor can be integrated into either a newly designed detachable high-throughput MetaSPR chip-strip plate device or a standard 96-well plate for multiplexed small-molecule detection within a single egg. The limits of detection were 0.81, 1.12, and 1.74 ppt for florfenicol, fipronil, and enrofloxacin, respectively, demonstrating up to 1000-fold increased sensitivity and a 15-fold reduction in analysis time compared with those of traditional methods. The results obtained using the APNMSPR biosensor showed a strong correlation with those obtained using liquid chromatography-tandem mass spectrometry. The APNMSPR biosensor holds immense promise for the multiplexed, highly sensitive, and rapid quantitative analysis of small molecules for applications in food safety control, early diagnosis, and environmental monitoring., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Development and validation of a predictive model including serum vitamin concentration to estimate the risk of chemotherapy-induced grade 3/4 neutropenia in esophageal cancer, gastric cancer, or colorectal cancer patients who receive the first cycle of chemotherapy., Methods: Data from 535 patients treated at the Affiliated Fuyang People's Hospital of Anhui Medical University from January 1, 2020, to March 2, 2022, were used to derive the predictive model. Least absolute shrinkage and selection operator regression analysis was performed to screen potential risk characteristics, and multivariate logistic regression was utilized to investigate efficient factors associated with chemotherapy-induced neutropenia. A nomogram was constructed using this logistic model. This nomogram was then tested on a temporal validation cohort containing 212 consecutive patients., Results: In the cohort of all 747 eligible patients, grade 3/4 neutropenia incidence was 45.2%. Age, Eastern Cooperative Oncology Group-performance status, neutrophil count, serum albumin, and hemoglobin data were entered into the final model. The performance of the final predictive nomogram was assessed by the area under the receiver operating characteristic curve in both the development and validation datasets. The calibration curves indicated that the estimated risks were accurate. Decision curve analysis for the predictive model exhibited improved clinical practicality., Conclusion: In the present study, we established an accessible risk predictive model and identified valuable serum vitamin concentration parameters associated with chemotherapy-induced neutropenia. The predictive model may improve the grade 3/4 neutropenia risk prediction in patients with gastrointestinal malignancies who receive oxaliplatin- and fluoropyrimidine-based chemotherapy and help physicians make appropriate decisions for disease management., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Supplemental materialSupplemental material for this article is available online.

Uniaxial cyclic compression tests were performed to investigate the compression deformation and damage of polymer-bonded explosive (PBX) simulant, particularly shear localization. The macroscopic mechanical behavior and mesoscale failure mechanisms of the PBX simulant were analyzed by optical observation and SEM scanning methods. After each cyclic compression, the specimen was scanned by X-ray computed tomography (CT), and the internal 3D deformation of the specimen was calculated using the digital volume correlation (DVC) method. The results show that the stress-strain curve of the PBX simulant exhibits five stages and coincides with the morphological changes on the surface of the specimen. The mesoscale failure mechanism is dominated by particle interface debonding and binder tearing, accompanied by a small amount of particle breakage. There are three bifurcation points (T 1 , T 2 , and T 3 ) in the curves of the normal and shear strain components with compression strain. It was found that these bifurcation points can reflect the full progression of the specimen from inconspicuous damage to uniformly distributed damage, shear localization, and eventual macroscopic fracture. The strain invariant I 1 can quantitatively and completely characterize the deformation and damage processes of the PBX simulant under cyclic compression., Competing Interests: The authors declare no conflicts of interest.

Background: Accurate preoperative judgment of lymph node (LN) metastasis is a critical step in creating a treatment strategy and evaluating prognosis in rectal cancer (RC) patients., Objective: This study aimed to explore the value of T1 mapping and amide proton transfer weighted (APTw) imaging in predicting LN metastasis in patients with rectal cancer., Methods: In a retrospective study, twenty-three patients with pathologically confirmed rectal adenocarcinoma who underwent MRI and surgery from August 2019 to August 2021 were selected. Then, 3.0T/MR sequences included conventional sequences (T1WI, T2WI, and DWI), APTw imaging, and T1 mapping. Patients were divided into LN metastasis (group A) and non-LN metastasis groups (group B). The intra-group correlation coefficient (ICC) was used to test the inter-observer consistency. Mann-Whitney U test was used to compare the differences between the two groups. Spearman correlation analysis was performed to evaluate the correlation between T1 and APT values. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the differential performance of each parameter and their combination. The difference between AUCs was compared using the DeLong test., Results: The APT value in patients with LN metastasis was significantly higher than in those without LN metastasis group (P=0.020). Also, similar results were observed for the T1 values (P=0.001). The area under the ROC curve of the APT value in the prediction of LN metastasis was 0.794; when the cutoff value was 1.73%, the sensitivity and specificity were 71.4% and 88.9%, respectively. The area under the ROC curve of the T1 value was 0.913; when the cutoff value was 1367.36 ms, the sensitivity and specificity were 78.6% and 100.0%, respectively. The area under the ROC curve of T1+APT was 0.929, with a sensitivity of 78.6% and specificity of 100.0%., Conclusion: APT and T1 values show great diagnostic efficiency in predicting LN metastasis in rectal cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background Context: Facet joint osteoarthritis (FJOA) is associated with lumbar disc degeneration and has a significant role in the development of lumbar spinal stenosis (LSS). The relationship between various radiographic parameters and the grade of FJOA is not well understood., Purpose: To explore radiographical parameters associated with FJOA in LSS without lumbar dynamic instability., Study Design: Retrospective study analysis., Patient Sample: A total of 122 patients diagnosed with LSS who visited our hospital between January 2015 and July 2022., Outcome Measures: We evaluated radiographic parameters of patients at L4-5 including lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), grades of FJOA, facet joint orientation (FO), facet joint tropism (FT), intervertebral height index (IHI) and the relative cross-sectional area (RCSA) of paraspinal muscles., Methods: Patients diagnosed with LSS between January 2015 and July 2022 were enrolled. Demographic characteristics and radiographic parameters were collected. Spinopelvic parameters were measured through the preoperative lateral image of the whole spine, including LL, PI, pelvic tilt, and sacral slope. Lumbar computed tomography scan and magnetic resonance imaging were collected to measure the FO, FT, IHI, and the RCSA of paraspinal muscles respectively. Patients were divided into three groups according to the severity of FJOA graded by the Weishaupt classification: grade 0 and grade 1 were group A, grade 2 were group B, and grade 3 were group C. All variables were compared among the three groups, while the relationship between parameters and grades of FJOA were also analyzed., Results: A total of 122 patients were included. PI was significantly greater in group C compared to group A (p = 0.025) and group B (p=0.022). FT was significantly greater in group C compared to group A (p<.001) and group B (p<.001). The RCSA of multifidus in group A were significantly greater than that in group B (p=0.02) and C (p=0.002). Additionally, FO in group C were significantly lower than group A (p<.001) and group B (p=0.028). The IHI in group C was significantly lower than group A (p=0.017). The correlation analysis indicated that grades of FJOA was positively related to Age, BMI (body mass index), PI, LL and FT, while negatively related to IHI, FO, RCSA of multifidus and RCSA of psoas major. Furthermore, the logistics regression showed that FT, PI, and IHI were important influence factors for FJOA., Conclusions: The current study confirmed that FT, PI and IHI were significantly associated with grades of FJOA at L4-5. Additionally, longitudinal studies are needed to understand the causal relationship between these parameters and FJOA., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Along with the gradually increasing incidence, nonalcoholic fatty liver disease (NAFLD) has already been influencing the health of more and more people in the world. Corydalis saxicola Bunting (CSB), a valuable folk medicine, is the dried whole grass of a perennial herb, Yanhuanglian (Papaveraceae), which has significant effects on various hepatitis, liver fibrosis, cirrhosis and other liver diseases. Corydalis saxicola Bunting total alkaloids (CSBTA), a mixture of alkaloids extracted from CSB, exhibit widely-accepted hepatoprotective effects., Aim of the Study: This study aimed to explore the therapeutic potential of CSBTA on NAFLD and the underlying mechanism., Materials and Methods: A mice model was established by high fat and high cholesterol diet (HFHCD) to study the benefits of CSBTA on the progression of NAFLD. The efficacy of CSBTA on NAFLD was revealed systematically via RNA-sequencing analysis. Further efficacy and molecular mechanism study were explored in mouse primary hepatocytes and HepG2 cells stimulated with high energy with or without pharmacological inhibition or gene silencing., Results: CSBTA effectively improved the major hallmarks of NAFLD including liver lipid accumulation, liver injury, inflammation and fibrosis in HFHCD-fed mice. RNA sequencing and targeted qPCR analysis jointly evidenced CSBTA significantly suppressed the expression of Srebf1, Acc1 and Fasn which are the genes responsible for fatty acid biosynthesis. Moreover, stable isotope tracer test denoted CSBTA reduced lipid accumulation via interrupting fatty acid biosynthesis in hepatocytes or the liver. Mechanistically, CSBTA could impede SREBP1 maturation via AMPK activation, thereby reducing DNL-derived lipid accumulation in hepatocytes., Conclusions: CSBTA protected against hepatic steatosis and other hallmarks of NAFLD induced by HFHCD via suppressing DNL, through modulating the AMPK-SREBP1 axis. CSBTA may therefore have a therapeutic potential for NAFLD treatment., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Osteoporosis is a metabolic bone loss disorder usually accompanied by overactivated osteoclast formation and increased bone resorption. Transcriptional co-activator with PDZ-binding motif (TAZ) is an emerging potential target for the treatment of osteoporosis. Our previous research showed that TAZ overexpression inhibited osteoclast formation while TAZ silencing had the opposite effect. In addition, TAZ knockout in mouse osteoclasts induced osteoporosis in animal experiments. XMU-MP-1 (XMU) is a selective MST1/2 inhibitor that can theoretically activate TAZ; however, its effect on osteoporosis remains unknown. In this study, we found that XMU treatment significantly increased TAZ expression in osteoclasts and inhibited osteoclast formation in vitro; however, this inhibitory effect was eliminated after the deletion of TAZ. Furthermore, XMU treatment upregulated TAZ expression in osteoclasts and alleviated ovariectomy (OVX)-induced osteoporosis in bilateral OVX mouse models. These findings suggest that XMU can effectively activate TAZ and that pharmacological activation of TAZ may be a promising option for the treatment of osteoporosis., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Responsive drug delivery systems hold great promise for tumor treatment as they focus on therapeutic agents directly, thus minimizing systemic toxicities and drug leakage. In this study, we covalently bound a matrix metalloproteinases-2 (MMP-2) enzyme-sensitive peptide to a tissue-penetrating peptide to rationally design a MMP-2 responsive multifunctional peptide hydrogel platform (aP/IR@FMKB) for cancer photothermal-chemo-immunotherapy. The constructed aP/IR@FMKB with bufalin (BF) loaded in trimethyl chitosan nanoparticles (TB NPs), photothermal agent IR820, and immune checkpoint inhibitor aPD-L1 by self-assembly could be dissociated in the presence of MMP-2 enzyme, triggering content release., Methods: TB NPs, IR820, and aPD-L1 were encapsulated by intermolecular self-assembly and enzyme-sensitive nanogels (aP/IR@FMKB) were constructed. The in vitro cytotoxicity of the blank gels and their ability to induce immunogenic cell death (ICD) in aP/IR@FMKB were evaluated using 4T1 cells. The promotion of deep tumor penetration and enzyme responsiveness was analyzed using a 3D cell model. The retention and antitumor activity at the tumor sites were examined using the primary tumor model. To assess the antitumor effect of aP/IR@FMKB induced by the immune response and its mechanism of action, recurrent tumor and distal tumor models were constructed., Results: This hydrogel system demonstrated exceptional photothermal performance and displayed prolonged local retention. Furthermore, the induction of ICD through IR820 and TB NPs sensitized the PD-L1 blockade, resulting in a remarkable 3.5-fold and 5.2-fold increase in the frequency of intratumor-infiltrating CD8 + T-cells in the primary tumor and distal tumor, respectively. Additionally, this system demonstrated remarkable efficacy in suppressing primary, distal, and recurrent tumors, underscoring its potential as a highly potent therapeutic strategy., Conclusion: This innovative design of the responsive hydrogel can effectively modulate the tumor immune microenvironment while also demonstrating sensitivity to the PD-1/PD-L1 blockade. This significant finding highlights the promising potential of this hydrogel in the field of multimodal tumor therapy., Competing Interests: All authors have no conflicts of interest for this work to disclose., (© 2024 Zhang et al.)

Purpose: To investigate the function and mechanism of tumor protein p53 in pathological scarring after glaucoma filtration surgery (GFS) using human Tenon's fibroblasts (HTFs) and a rabbit GFS model., Methods: The expression of p53 in bleb scarring after GFS and transforming growth factor-β (TGF-β)-induced HTFs (myofibroblasts [MFs]) was examined by western blot and immunochemical analysis. The interaction between p53 and specificity protein 1 (Sp1) was investigated by immunoprecipitation. The role of p53 and Sp1 in the accumulation of collagen type I alpha 1 chain (COL1A1) and the migration of MFs was evaluated by western blot, quantitative real-time polymerase chain reaction (qRT-PCR), wound healing, and Transwell assay. The regulatory mechanisms among p53/Sp1 and miR-29b were detected via qRT-PCR, western blot, luciferase reporter assay, and chromatin immunoprecipitation assay. The therapeutic effect of mithramycin A, a specific inhibitor of Sp1, on scarring formation was evaluated in a rabbit GFS model., Results: p53 was upregulated in bleb scar tissue and MFs. p53 and Sp1 form a transcription factor complex that induces the accumulation of COL1A1 and promotes the migration of MFs through downregulation of miR-29b, a known suppressor of COL1A1. The p53/Sp1 axis inhibits miR-29b expression by the direct binding promoter of the miR-29b gene. Mithramycin A treatment attenuated bleb scar formation in vivo., Conclusions: The p53/Sp1/miR-29b signaling pathway plays a critical role in bleb scar formation after GFS. This pathway could be targeted for therapeutic intervention of pathological scarring after GFS., Translational Relevance: Our research indicates that inhibition of p53/Sp1/miR-29b is a promising therapeutic strategy for preventing post-GFS pathological scarring.

The hepatic SLC13A5/SLC25A1-ATP-dependent citrate lyase (ACLY) signaling pathway, responsible for maintaining the citrate homeostasis, plays a crucial role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Bempedoic acid (BA), an ACLY inhibitor commonly used for managing hypercholesterolemia, has shown promising results in addressing hepatic steatosis. This study aimed to elucidate the intricate relationships in processes of hepatic lipogenesis among SLC13A5, SLC25A1, and ACLY and to examine the therapeutic potential of BA in NAFLD, providing insights into its underlying mechanism. In murine primary hepatocytes and HepG2 cells, the silencing or pharmacological inhibition of SLC25A1/ACLY resulted in significant upregulation of SLC13A5 transcription and activity. This increase in SLC13A5 activity subsequently led to enhanced lipogenesis, indicating a compensatory role of SLC13A5 when the SLC25A1/ACLY pathway was inhibited. However, BA effectively counteracted this upregulation, reduced lipid accumulation, and ameliorated various biomarkers of NAFLD. The disease-modifying effects of BA were further confirmed in NAFLD mice. Mechanistic investigations revealed that BA could reverse the elevated transcription levels of SLC13A5 and ACLY, and the subsequent lipogenesis induced by PXR activation in vitro and in vivo. Importantly, this effect was diminished when PXR was knocked down, suggesting the involvement of the hepatic PXR-SLC13A5/ACLY signaling axis in the mechanism of BA action. In conclusion, SLC13A5-mediated extracellular citrate influx emerges as an alternative pathway to SLC25A1/ACLY in the regulation of lipogenesis in hepatocytes, BA exhibits therapeutic potential in NAFLD by suppressing the hepatic PXR-SLC13A5/ACLY signaling axis, while PXR, a key regulator in drug metabolism may be involved in the pathogenesis of NAFLD. SIGNIFICANCE STATEMENT: This work describes that bempedoic acid, an ATP-dependent citrate lyase (ACLY) inhibitor, ameliorates hepatic lipid accumulation and various hallmarks of non-alcoholic fatty liver disease. Suppression of hepatic SLC25A1-ACLY pathway upregulates SLC13A5 transcription, which in turn activates extracellular citrate influx and the subsequent DNL. Whereas in hepatocytes or the liver tissue challenged with high energy intake, bempedoic acid reverses compensatory activation of SLC13A5 via modulating the hepatic PXR-SLC13A5/ACLY axis, thereby simultaneously downregulating SLC13A5 and ACLY., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

Objective . In the field of motor imagery (MI) electroencephalography (EEG)-based brain-computer interfaces, deep transfer learning (TL) has proven to be an effective tool for solving the problem of limited availability in subject-specific data for the training of robust deep learning (DL) models. Although considerable progress has been made in the cross-subject/session and cross-device scenarios, the more challenging problem of cross-task deep TL remains largely unexplored. Approach . We propose a novel explainable cross-task adaptive TL method for MI EEG decoding. Firstly, similarity analysis and data alignment are performed for EEG data of motor execution (ME) and MI tasks. Afterwards, the MI EEG decoding model is obtained via pre-training with extensive ME EEG data and fine-tuning with partial MI EEG data. Finally, expected gradient-based post-hoc explainability analysis is conducted for the visualization of important temporal-spatial features. Main results . Extensive experiments are conducted on one large ME EEG High-Gamma dataset and two large MI EEG datasets (openBMI and GIST). The best average classification accuracy of our method reaches 80.00% and 72.73% for OpenBMI and GIST respectively, which outperforms several state-of-the-art algorithms. In addition, the results of the explainability analysis further validate the correlation between ME and MI EEG data and the effectiveness of ME/MI cross-task adaptation. Significance . This paper confirms that the decoding of MI EEG can be well facilitated by pre-existing ME EEG data, which largely relaxes the constraint of training samples for MI EEG decoding and is important in a practical sense., (© 2023 IOP Publishing Ltd.)

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality. Human phenylalanine tRNA synthetase (PheRS) comprises two α catalytic subunits encoded by the FARSA gene and two β regulatory subunits encoded by the FARSB gene. FARSB is a potential oncogene, but no experimental data show the relationship between FARSB and HCC progression. We found that the high expression of FARSB in liver cancer is closely related to patients' low survival and poor prognosis. In liver cancer cells, the mRNA and protein expression levels of FARSB are increased and promote cell proliferation and migration. Mechanistically, FARSB activates the mTOR complex 1 (mTORC1) signaling pathway by binding to the component Raptor of the mTORC1 complex to play a role in promoting cancer. In addition, we found that FARSB can inhibit erastin-induced ferroptosis by regulating the mTOR signaling pathway, which may be another mechanism by which FARSB promotes HCC progression. In summary, FARSB promotes HCC progression and is associated with the poor prognosis of patients. FARSB is expected to be a biomarker for early screening and treatment of HCC.

Osteoarthritis is a common chronic degenerative disease, of which the essence is the degenerative changes of bone and joint cartilage, involving damage in multiple structures such as bone, synovium and joints. In the mechanism of arthritis inflammation is closely related, and therefore the exploration to inhibit inflammatory mediators is crucial for the clinical prevention and treatment of osteoarthritis. Inotodiol is a lanostane triterpenoid isolated from Inonotus obliquus, which had been extensively reported to be an anti-inflammatory agent, but its effect on arthritis remains unknown. In this study, we firstly demonstrated that inotodiol significantly reduced IL-1β-induced chondrocyte injury and inhibited the release of inflammatory factors. At the same time, experiments in vivo showed that inotodiol could effectively improve the symptoms of joint injury in mice and reduce the area of cartilage destruction, indicating that inotodiol may be a potential therapeutic drug for osteoarthritis., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Nuclear respiratory factor 1 (NRF1) is a transcription factor that participates in several kinds of tumor, but its role in hepatocellular carcinoma (HCC) remains elusive. This study aims to explore the role of NRF1 in HCC progression and investigate the underlying mechanisms., Results: NRF1 was overexpressed and hyperactive in HCC tissue and cell lines and high expression of NRF1 indicated unfavorable prognosis of HCC patients. NRF1 promoted proliferation, migration and invasion of HCC cells both in vitro and in vivo. Mechanistically, NRF1 activated ERK1/2-CREB signaling pathway by transactivating lysophosphatidylcholine acyltransferase 1 (LPCAT1), thus promoting cell cycle progression and epithelial mesenchymal transition (EMT) of HCC cells. Meanwhile, LPCAT1 upregulated the expression of NRF1 by activating ERK1/2-CREB signaling pathway, forming a positive feedback loop., Conclusions: NRF1 is overexpressed in HCC and promotes HCC progression by activating LPCAT1-ERK1/2-CREB axis. NRF1 is a promising therapeutic target for HCC patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

In many practice application, the cost for acquiring abnormal data is quite expensive, thus the one-class classification (OCC) problem attracts great attention. As one of the solutions, support vector data description (SVDD) gains a continuous focus in outlier detection since it is based on the data description. For the sphere obtained by SVDD, both the center and the volume (or radius) strongly depend on the support vectors, while the support vectors are sensitive to the tradeoff parameter C . Hence, how to select this parameter is a rather challenging problem. In order to address this problem, we define several distance metrics relative to the image region in Gaussian kernel space. With the distance metrics, two probability densities relative to the global region and the local region are designed, respectively. Then, the information quantity and the information entropy are developed for regularizing the tradeoff parameter. This novel SVDD is called global plus local jointly regularized support vector data description (GL-SVDD), in which both the global region information and the local image region information jointly penalize the images as possible outliers. Finally, we use the UCI dataset and the hyperspectral data of cherry fruit to evaluate the performance of several OCC approaches. Experimental results show that GL-SVDD is encouraging.

Sulfur has a high affinity for mercury (Hg) and can serve as effective treating agent for Hg pollution. However, conflict effects between reducing Hg mobility and promoting Hg methylation by sulfur were found in recent studies, and there is a gap in understanding the potential mechanism of MeHg production under different sulfur-treated species and doses. Here, we investigated and compared the MeHg production in Hg-contaminated paddy soil and its accumulation in rice under elemental sulfur or sulfate treatment at a relatively low (500 mg·kg -1 ) or high (1000 mg·kg -1 ) level. The associated potential molecular mechanisms are also discussed with the help of density functional theory (DFT) calculation. Pot experiments demonstrate that both elemental sulfur and sulfate at high exposure levels increased MeHg production in soil (244.63-571.72 %) and its accumulation in raw rice (268.73-443.50 %). Coupling the reduction of sulfate or elemental sulfur and decrease of soil redox potential leads to the detachment of Hg-polysulfide complexes from the surface of HgS which can be explained by DFT calculations. Enhancement of free Hg and Fe release through reducing Fe(III) oxyhydroxides further promotes soil MeHg production. The results provide clues for understanding the mechanism by which exogenous sulfur promotes MeHg production in paddies and paddy-like environments and give new insights for decreasing Hg mobility by regulating soil conditions., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 Elsevier B.V. All rights reserved.)