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Objective: To investigate the anti-adhesive effect and underlying mechanism of dynamic and static stress stimulation on the early healing process of rat Achilles tendon injury., Methods: Achilles tendon tissues of 15 male Sprague Dawley (SD) rats aged 4-6 weeks were isolated and cultured by enzyme digestion method. Rat Achilles tendon cells were treated with tumor necrosis factor α to construct the Achilles tendon injury cell model, and dynamic stress stimulation (dynamic group) and static stress stimulation (static group) were applied respectively, while the control group was not treated. Live/dead cell double staining was used to detect cell activity, ELISA assay was used to detect the expression of α smooth muscle actin (α-SMA), and real-time fluorescence quantitative PCR was used to detect the mRNA expression of collagen type Ⅰ (COL1A1), collagen type Ⅲ (COL3A1), and Scleraxis (SCX). Thirty male SD rats aged 4-6 weeks underwent Achilles tendon suture and were randomly divided into dynamic group (treated by dynamic stress stimulation), static group (treated by static stress stimulation), and control group (untreated), with 10 rats in each group. HE staining and scoring were performed to evaluate the healing of Achilles tendon at 8 days after operation. COL1A1 and COL3A1 protein expressions were detected by immunohistochemical staining, α-SMA and SCX protein expressions were detected by Western blot, and maximum tendon breaking force and tendon stiffness were detected by biomechanical stretching test., Results: In vitro cell experiment, when compared to the static group, the number of living cells in the dynamic group was higher, the expression of α-SMA protein was decreased, the relative expression of COL3A1 mRNA was decreased, and the relative expression of SCX mRNA was increased, and the differences were all significant ( P <0.05). In the in vivo animal experiment, when compared to the static group, the tendon healing in the dynamic group was better, the HE staining score was lower, the expression of COL1A1 protein was increased, the expression of COL3A1 protein was decreased, the relative expression of SCX protein was increased, the relative expression of α-SMA protein was decreased, and the tendon stiffness was increased, the differences were all significant ( P <0.05)., Conclusion: Compared with static stress stimulation, the dynamic stress stimulation improves the fibrosis of the scar tissue of the rat Achilles tendon, promote the recovery of the biomechanical property of the Achilles tendon, and has obvious anti-adhesion effect.

A focused chemical investigation into the polar fractions of a well-known traditional Chinese medicine called Sang-Bai-Pi (the root bark of Morus alba) yielded a panel of prenylated flavanones. The new compounds were identified as four pairs of enantiomers (1a/1b-4a/4b) featuring the same constitution structure, on the basis of HRMS, NMR and ECD analyses. Several previously reported known racemic co-metabolites were also analyzed and separated by HPLC on chiral columns, and the absolute configurations of pure enantiomers were established via ECD technique for the first time. The inhibition of these isolates against the antidiabetic target α-glycosidase was further tested, with most of them showing decent inhibitory activity compared with the positive control acarbose. The interaction mechanism of two selected compounds (3a & 4b) was explored by kinetics experiment, which revealed a mixed type of inhibition pattern toward the enzyme., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

High inhibitor concentrations in lignocellulose feedstock negatively affect the degradation rate of biodetoxification strains. This study designed two adaptive laboratory evolutions in solid substrate and liquid medium to boost the biodetoxification capacity of P. variotii to high titers of lignocellulose-derived inhibitors, resulting in two evolved strains AC70 and ZW70. The results showed that the evolutionary adaptation in liquid medium could better boost the acetic acid assimilation compared to that on solid substrate. Transcriptional analysis revealed that the evolved strains exhibited a significant upregulation of adh, acs, ach1, and ackA directly related to the initial steps of acetate and furan aldehydes metabolisms. ZW70 strain can effectively remove the high concentration inhibitors cocktail from the hydrolysates derived from pretreated wheat straw and furfural residues. The biodetoxified hydrolysates by ZW70 were successfully used for cellulose chiral L-lactic acid production with the titers of ∼110 g/L, which were over 20 % higher than that detoxified by parental strain., 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 Ltd. All rights reserved.)

Background: Compared with open radical prostatectomy (RP), laparoscopic or robot-assisted RP have shown a notable decrease in the incidence of organ dysfunction or potentially life-threating complications after surgery. However, despite advances, the postoperative length of hospital stay (LOS) remains longer than desired in many cases. The Postoperative Morbidity Survey (POMS) is a simple approach to detect complications capable of prolonging LOS. The primary objective of this study was to outline the incidence and type of early morbidity following laparoscopic or robot-assisted RP using modified POMS(m-POMS). The secondary objective was to investigate the correlation between m-POMS and postoperative LOS., Methods: A retrospective study of the electronic health records was performed for all eligible patients undergoing laparoscopic or robot-assisted RP over a one-year period (August 1, 2022 to July 31, 2023). Morbidity as defined by m-POMS was collected on postoperative day 1 (POD1), POD3, POD5 and POD8. Poisson regression models were employed to assess the correlation between positive m-POMS and postoperative LOS., Results: A total of 121 patients were included. Morbidity, as measured by m-POMS, occurred on POD1 (19.01%, 95% CI [13.01%, 26.91%]), POD3 (18.81%, 95% CI [12.39%, 27.52%]), POD5 (30.23%, 95% CI [18.60%, 45.10%]) and POD8 (35.29%, 95% CI [17.31%, 58.70%]). Two prevalent domains with positive m-POMS scores were infectious and pulmonary. The occurrence of morbidity as indicated by m-POMS was correlated with longer median (IQR) postoperative LOS on POD1 7 (5, 9) versus 4 (4, 6), POD3 7 (6, 11) versus 5(4, 6), and POD5 11 (6.5, 11) versus 7(6, 9) (p < 0.05) compared with patients who did not encounter m-POMS-assessed morbidity. Regression analysis showed that m-POMS-defined morbidity was correlated with longer postoperative LOS on POD1 and POD3., Conclusions: The incidence of early morbidity, as defined by m-POMS following radical prostatectomy, was approximately 20%, with infectious and pulmonary complications being the most prevalent. Short-term morbidity assessed by m-POMS was significantly associated with prolonged LOS., (© 2024. The Author(s).)

To investigate the potential link between gut microbiota and functional dyspepsia (FD). Genome-wide association studies (GWAS) of gut microbiota and FD were used in Mendelian randomization (MR) research. Using the GWAS of 18,340 people, instrumental variables related to gut microbiota as an exposure factor were identified. In a GWAS investigation, 189,695 control individuals and 4376 FD patients were included as outcome variables. The primary analysis technique was inverse variance weighted analysis. The reliability of MR analysis results is tested using sensitivity analysis. Two-sample Mendelian randomization analysis revealed the presence of 7 gut microbiota associated to FD. In the inverse variance weighted analysis method, Order Erysipelotrichales (odds ratio (OR): 1.301; 95% confidence interval (CI): 1.016, 1.665; P = .037), Family Erysipelotrichales (OR: 1.301; 95% CI: 1.016, 1.665; P = .037), Genus Haemophilus (OR: 1.236; 95% CI 1.059, 1.442; P = .007), Genus Ruminiclostridium 9 (OR: 1.422; 95% CI: 1.078, 1.877; P = .013), Genus Lachnospiraceae NK4A 136 group (OR: 1.297; 95% CI: 1.059, 1.589; P = .012) was positively associated with FD. Class Gammaproteobacteria (OR: 0.705; 95% CI: 0.522, 0.952; P = .022) and Genus Erysipelatoclostridium (OR: 0.747; 95% CI: 0.628, 0.888; P = .001) were found to be inversely related to FD. There was no evidence of pleiotropy or heterogeneity in the sensitivity analysis. Our research provides evidence for a possible link between FD and a number of gut microbiota. The role that gut microbiota plays in the development of FD requires more investigation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Polygonum multiflorum-induced liver injury (PM-DILI) has significantly hindered its clinical application and development., Methods: This study investigates the variation in content and toxicity of dianthrones, the toxic components of P. multiflorum, during different processing cycles. We employed the ultra-high-performance liquid chromatography triple quadrupole mass spectrometry method to quantify six dianthrones in raw P. multiflorum and formulations processed with a method called nine cycles of steaming and sunning. Additionally, toxicity assessments were conducted using human normal liver cell line L02 and zebrafish embryos., Results: Results indicate a gradual reduction in dianthrones content with increasing processing cycles. Processed formulations exhibited significantly reduced cytotoxicity in L02 cells and hepatotoxicity in zebrafish embryos., Conclusions: Our findings elucidate the relationship between processing cycles and P. multiflorum toxicity, providing theoretical support for its safe use., (© 2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Spectrometer miniaturization has become a significant trend driven by the demand for distributed and continuous spectral sensing. Broadband encoding spectrometers, which utilize broadband encoder arrays to extract spectral features and algorithms to reconstruct spectra, are among the most competitive candidates for high-performance miniaturized spectrometers. Enhancing the spectral feature extraction capability of these broadband encoders is essential for improving spectrometer performance. However, the strategies and approaches for optimizing these encoders are not yet well-defined. This study analyzes the effectiveness of improving the basis orthogonality of the encoders for their optimization and proposes a dual-layer broadband encoder structure to implement this optimization strategy. The designed dual-layer broadband encoders consist of vertically stacked quantum dot encoders and TiO 2 /SiO 2 encoders, with the corresponding basis being mixed Gaussian. Simulation experiments demonstrate that the proposed dual-layer broadband encoder structure significantly improves the encoders' basis orthogonality, leading to enhanced spectral detection accuracy of the spectrometer constructed with these dual-layer encoders. Experimental fabrication of the dual-layer encoders confirms their physical feasibility and basis orthogonality enhancement.

Under the guidance of MS/MS-based molecular networking, five new clerodane diterpenoid glucosides, tinosinesides R-V (1-5), along with 15 known diterpenoids (6-20), were isolated from the stems of Tinospora sinensis. Compound 1 represents the first example of diterpenoid bearing a thio sugar and compound 5 is the first 18,19-dinor-clerodane with cis-fused A/B ring. The structures of the new compounds were elucidated by spectroscopic means, and their absolute configurations were established on the basis of time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculation and chemical methods. Selected compounds were evaluated for their immunomodulatory effect and several compounds could enhance the proliferation of B lymphocytes. Preliminary mechanistic studies disclosed that 3 could promote B cell generation and inhibit B cell differentiation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

L-lactic acid fermentation at low pH reduces the use of neutralizers during fermentation and the generation of solid wastes in purification processes. Most lactic acid bacteria exhibit weak tolerance and poor cell viability at low pH. This study proposes a pH shifting adaptive evolution method to improve the low-pH tolerance of an engineered Pediococcus acidilactici strain. In the first stage, cells were cultured at a moderate pH to maintain the cell viability, then shifted to a low pH to enhance low-pH tolerance. Long-term pH shifting evolution culture of the engineered P. acidilactici between the moderate and low pH resulted in a 43 % increase in L-lactic acid production at pH 4.6 (110.4 g/L) and a 2.1-fold increase at pH 4.4 (80.7 g/L) compared to the parental strain when using wheat straw as a feedstock. This pH-shifting adaptive evolution strategy provides an effective tool for improving the low-pH tolerance of lactic acid bacteria., 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 Ltd. All rights reserved.)

Nicotinamide adenine dinucleotide (NAD + ) is a crucial coenzyme involved in catalyzing cellular redox reactions and serving as a substrate for NAD + -dependent enzymes. It plays a vital role in maintaining tissue homeostasis and promoting healthy aging. Exercise, a well-established and cost-effective method for enhancing health, can influence various pathways related to NAD + metabolism. Strategies such as supplementing NAD + precursors, modulating NAD + synthesis enzymes, or inhibiting enzymes that consume NAD + can help restore NAD + balance and improve exercise performance. Various overlapping signaling pathways are known to play a crucial role in the beneficial effects of both NAD + and exercise on enhancing health and slowing aging process. Studies indicate that a combined strategy of exercise and NAD + supplementation could synergistically enhance athletic capacity. This review provides an overview of current research on the interactions between exercise and the NAD + network, underscoring the significance of NAD + homeostasis in exercise performance. It also offers insights into enhancing exercise capacity and improving aging-related diseases through the optimal use of exercise interventions and NAD + supplementation methods., Competing Interests: Declarations of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background: The rapid and accurate acquisition of prostate cancer pathological tissue is critical to prostate cancer research but has traditionally proven challenging. However, the gradual application of three-dimensional (3D) modeling in medical practice has overcome many of the related limitations. This cohort study aimed to compare the difference between a 3D stereotaxic sampling method and traditional cognitive sampling method to clarify the factors affecting sampling., Methods: An analysis of 111 men who received radical prostatectomy for prostate cancer at The First Affiliated Hospital of Soochow University between November 2020 and April 2022 was conducted. The positive rate of the cognitive sampling method and the 3D stereotaxic sampling method and their respective influencing factors, such as age, body mass index (BMI), prostate-specific antigen (PSA), PSA density (PSAD), International Society of Urological Pathology (ISUP) grade, tumor volume, number of positive needles from perineal puncture, clinical T stage, and tumor image location, were compared and analyzed, and a cohort study was conducted., Results: Among the 111 patients, there were 57 cases of cognitive sampling and 54 cases of 3D stereotaxic sampling. In this study, the positive rate of cognitive sampling was 29.82% (17/57,), and the positive rate of 3D stereotaxic sampling was 61.11% (33/54), with the positive rate of 3D stereotaxic sampling being significantly higher than that of cognitive sampling (P=0.001). In cognitive sampling, tumor volume [odds ratio (OR) =1.10; 95% confidence interval (CI): 1.02-1.20], number of positive biopsy cores (OR =1.30; 95% CI: 1.06-1.60), Prostate Imaging Report and Data System (PI-RADS) score (OR =5.54; 95% CI: 1.60-19.12), and clinical T stage (OR =2.36; 95% CI: 1.31-4.25) were identified as influencing factors; in 3D stereotaxic sampling, these influencing factors were eliminated, with ORs of 1.22 (95% CI: 0.78-1.90), 0.88 (95% CI: 0.72-1.09), 1.09 (95% CI: 0.62-1.92), and 1.51 (95% CI: 0.86-2.65), respectively, representing a statistically significant difference (P<0.05)., Conclusions: The 3D stereotaxic sampling method can accurately obtain the required prostate cancer tissue from the prostate in vitro within a short time, and the factors affecting the positive rate of sampling can be eliminated., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1820/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Improving the cultivation mode and technology for traditional Chinese medicine has become important for its sustainable development. Monoculture enhances plant diseases, which decreases yield and quality. Intercropping is an effective measure to counterbalance that negative effect. In this study, we focused on Panax quinquefolium L. (ginseng) and four treatments were set up: the control without intercropping, P. quinquefolius + ryegrass (Lolium perenne L.), P. quinquefolius + red clover (Trifolium pratense L.), and P. quinquefolius + ryegrass + red clover. An LC-MS/MS system was used to detect the changes in the P. quinquefolius secondary metabolites, and high-throughput sequencing technology was used to determine the changes in the P. quinquefolius' rhizosphere soil microorganisms. Ginsenoside content, soil enzyme activities, and arbuscular mycorrhizal infection rate of P. quinquefolius were also measured using HPLC, ELISA kits, and microscopy, respectively. Co-intertia and Pearson's analysis were performed to explore the relationship between the metabolites and the P. quinquefolius microorganisms. Intercropping significantly increased the content of ginsenoside metabolites and recruited a large number of beneficial bacteria to the P. quinquefolius rhizosphere. The P. quinquefolius secondary metabolites were associated with the rhizosphere microbial community. For example, the dominant microorganisms, such as Acidobacteriota and Chloroflexi, played a key role in promoting the synthesis of ginsenoside Rd and (20R) ginsenoside Rg3 by P. quinquefolius. Intercropping led to changes in the P. quinquefolius secondary metabolites by driving and reshaping the rhizosphere microorganisms. These findings revealed the potential application of intercropping for improving the quality of P. quinquefolius., (© 2024 Scandinavian Plant Physiology Society.)

Background: Following the gastrectomy, the reduction in pulmonary function is partly attributed to postoperative pain. Subcostal quadratus lumborum block (QLB) has recently emerged as a promising component in multimodal analgesia. We aimed to assess the impact of intermittent boluses of subcostal QLB on pulmonary function recovery and analgesic efficacy after gastrectomy., Methods: Sixty patients scheduled for gastrectomy were randomly assigned to either control group (multimodal analgesia) or intervention group (intermittent boluses of subcostal QLB plus multimodal analgesia). Two primary outcomes included the preservation of forced expiratory volume in the first second (FEV1) and the pain scores (0-10 cm visual analog score) on coughing 24 h postoperatively. We assessed the pulmonary function parameters, pain score, morphine consumption and number of rescue analgesia at a 24-h interval up to 72 h (Day1, Day2, Day3 respectively) as secondary outcomes., Results: 59 patients were analyzed in a modified intention-to-treat set. The preservation of FEV1 (median difference: 4.0%, 97.5% CI: -5.7 to 14.9, P = 0.332) and pain scores on coughing (mean difference: 0.0 cm, 97.5% CI: -1.1 to 1.2, P = 0.924) did not differ significantly between two groups. In the intervention group, the recovery of forced vital capacity (FVC) was faster 72 h after surgery (interaction effect of group*(Day3-Day0): estimated effect (β) =0.30 L, standard error (SE) =0.13, P = 0.025), pain scores at rest were lower in the first 3 days (interaction effect of group*(Day1-Day0): β = - 0.8 cm, SE = 0.4, P = 0.035; interaction effect of group*(Day2-Day0): β = - 1.0 cm, SE = 0.4, P = 0.014; and interaction effect of group*(Day3-Day0): β = - 1.0 cm, SE = 0.4, P values = 0.009 respectively), intravenous morphine consumption was lower during 0-24 h (median difference: -3 mg, 95% CI -6 to -1, P = 0.014) and in total 72 h (median difference: -5 mg, 95% CI -10 to -1, P = 0.019), and the numbers of rescue analgesia was fewer during 24-48 h (median difference: 0, 95% CI 0 to 0, P = 0.043). Other outcomes didn't show statistical differences., Conclusion: Postoperative intermittent boluses of subcostal QLB did not confer advantages in terms of the preservation of FEV1 or pain scores on coughing 24 h after gastrectomy. However, notable effects were observed in analgesia at rest and FVC recovery., Competing Interests: Declaration of competing interest All authors declared that they have no conflict of interest., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Objective: To clarify the composition of lesions in different magnetic resonance imaging (MRI) partitions of positive surgical margins (PSM) after laparoscopic radical prostatectomy, explore the influence of lesion location on PSM, and construct a clinical prediction model to predict the risk of PSM., Materials and Methods: This retrospective cohort study included 309 patients who underwent laparoscopic radical prostatectomy from 2018 to 2021 in our center was performed. 129 patients who met the same criteria from January to September 2022 were external validation cohorts., Results: The incidence of PSM in transition zone (TZ) lesions was higher than that in peripheral zone (PZ) lesions. The incidence of PSM in the middle PZ was lower than that in other regions. Prostate specific antigen (PSA), clinical T-stage, the number of positive cores, international society of urological pathology (ISUP) grade (biopsy), MRI lesion location, extracapsular extension, seminal vesicle invasion (SVI), pseudo-capsule invasion (PCI), long diameter of lesions, lesion volume, lesion volume ratio, PSA density were related to PSM. MRI lesion location and PCI were independent risk factors for PSM. Least absolute shrinkage and selection operator (LASSO) regression was used to construct a clinical prediction model for PSM, including five variables: the number of positive cores, SVI, MRI lesion location, long diameter of lesions, and PSA., Conclusion: The positive rate of surgical margin in middle PZ was significantly lower than that in other regions, and MRI lesion location was an independent risk factor for PSM., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

The widespread use of antibiotics often increases bacterial resistance. Herein, we reported a silver peroxide-incorporated carbon dots (defined as Ag 2 O 2 -CDs) with high photothermal conversion efficiency via in situ oxidation process. The prepared Ag 2 O 2 -CDs exhibited ultra-small size of 2.0 nm and hybrid phase structure. Meanwhile, the Ag 2 O 2 -CDs were of a similar optical performance comparing with traditional carbon dots (CDs). Importantly, the incorporation of Ag 2 O 2 into CDs significantly enhanced photothermal conversion efficiency from 3.8% to 28.5%. By combining silver ion toxicity and photothermal ablation, the Ag 2 O 2 -CDs were capable of destroying gram-positive and gram-negative bacterium effectively. These findings demonstrated that the Ag 2 O 2 -CDs could be served as a potential antibacterial agent for clinical applications., (Creative Commons Attribution license.)

Active surveillance (AS) is the primary strategy for managing patients with low or favorable-intermediate risk prostate cancer (PCa). Identifying patients who may benefit from AS relies on unpleasant prostate biopsies, which entail the risk of bleeding and infection. In the current study, we aimed to develop a radiomics model based on prostate magnetic resonance images to identify AS candidates non-invasively. A total of 956 PCa patients with complete biopsy reports from six hospitals were included in the current multicenter retrospective study. The National Comprehensive Cancer Network (NCCN) guidelines were used as reference standards to determine the AS candidacy. To discriminate between AS and non-AS candidates, five radiomics models (i.e., eXtreme Gradient Boosting (XGBoost) AS classifier (XGB-AS), logistic regression (LR) AS classifier, random forest (RF) AS classifier, adaptive boosting (AdaBoost) AS classifier, and decision tree (DT) AS classifier) were developed and externally validated using a three-fold cross-center validation based on five classifiers: XGBoost, LR, RF, AdaBoost, and DT. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE) were calculated to evaluate the performance of these models. XGB-AS exhibited an average of AUC of 0.803, ACC of 0.693, SEN of 0.668, and SPE of 0.841, showing a better comprehensive performance than those of the other included radiomic models. Additionally, the XGB-AS model also presented a promising performance for identifying AS candidates from the intermediate-risk cases and the ambiguous cases with diagnostic discordance between the NCCN guidelines and the Prostate Imaging-Reporting and Data System assessment. These results suggest that the XGB-AS model has the potential to help identify patients who are suitable for AS and allow non-invasive monitoring of patients on AS, thereby reducing the number of annual biopsies and the associated risks of bleeding and infection., (© 2024. The Author(s).)

Azaphilones represent a particular group of fascinating pigments from fungal source, with easier industrialization and lower cost than the traditional plant-derived pigments, and they also display a wide range of pharmacological activities. Herein, 28 azaphilone analogs, including 12 new ones, were obtained from the fermentation culture of a marine fungus Penicillium sclerotium UJNMF 0503. Their structures were elucidated by MS, NMR and ECD analyses, together with NMR and ECD calculations and biogenetic considerations. Among them, compounds 1 and 2 feature an unusual natural benzo[d][1,3]dioxepine ring embedded with an orthoformate unit, while 3 and 4 represent the first azaphilone examples incorporating a novel rearranged 5/6 bicyclic core and a tetrahydropyran ring on the side chain, respectively. Our bioassays revealed that half of the isolates exhibited neuroprotective potential against H 2 O 2 -induced injury on RSC96 cells, while compound 13 displayed the best rescuing capacity toward the cell viability by blocking cellular apoptosis, which was likely achieved by upregulating the PI3K/Akt signaling pathway., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jie Bao, Yan-Fen Zhao, Hua Zhang, Shan-Shan Huang, Long Wang, Chun-Ying Wang, Yu Zhang has patent #Penicillium fungus and application thereof in preparing antibacterial medicine (CN115806881) issued to Jie Bao. Lei Zhou, Wen-Min Hou, Mei-Hui Hou, Jie Bao, Peng-Wei Jing, Hao Li, Yong-Mei Wu has patent #Extraction of nitrogenophilic ketone compound and its application(CN115850231) issued to Jie Bao. Jie Bao, Yan-Fen Zhao, Kongkai Zhu, Hua Zhang, Xin-Xin Wang, Ze-Long Chen, Ruo-Ping Ma has patent #Azone compounds and their preparation methods and their application in preparation of neuroprotective drugs (CN115851454) issued to Jie Bao. Jie Bao, Yan-Fen Zhao, Hua Zhang, Xin-Xin Wang, Shan-Shan Huang, Xin-Ping Liu has patent #Azurophilic ketone compounds with effect of promoting peripheral nerve injury repair and preparation method thereof (CN115960729) issued to Jie Bao. Xin-Ping Liu, Jie Bao, Ruo-Ping Ma, Long Wang, Yan-Fen Zhao, Xin-Xin Wang, Xin-Hui Cheng, Jia-Hui Xu has patent #Preparation of benzopyran compound and its application in preparation of medicine for neurodegenerative diseases (CN116410185) issued to Jie Bao. 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 Inc. All rights reserved.)

In the current work, grifolin was obtained from the twigs and leaves of Daphne genkwa for the first time and displayed significant growth inhibition against human lung carcinoma A549 cells. Subsequent in vitro antitumor evaluation revealed that grifolin could induce remarkable cell apoptosis and G 0 /G 1 phase arrest, as well as block cell migration and invasion. In addition, grifolin also disrupted cellular energy metabolism by inducing reactive oxygen species, reducing adenosine triphosphate and mitochondrial membrane potential, and damaging DNA synthesis. Further RNA-seq analysis demonstrated that treatment of grifolin on A549 cells led to gene enrichment in MAPK, PI3K/Akt and NF-κB signaling pathways, all of which were inhibited by grifolin according to immunoblotting experiments. Further mechanistical studies disclosed that the expression of a key upstream protein KRAS was also blocked, and the cell death triggered by grifolin could be rescued by a RAS activator ML-099. Moreover, pretreatment of ML-099 on A549 cells could reverse the grifolin-induced downregulation of key proteins in the three aforementioned pathways. These findings indicate that grifolin could induce cell death in A549 cell line by inhibiting KRAS-mediated multiple signaling pathways., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Sepsis is a life-threatening condition marked by a severe systemic response to infection, leading to widespread inflammation, cellular signaling disruption, and metabolic dysregulation. The role of lipid and amino acid metabolism in sepsis is not fully understood, but aberrations in this pathway could contribute to the disease's pathophysiology., Methods: To explore the potential of lipid and amino acid compounds as biomarkers for the diagnosis and prognosis of sepsis, a two-sample Mendelian Randomization (MR) study was conducted, examining the relationship between sepsis and 249 serum lipid and amino acid-related markers. Key enzymes involved in synthesis of phosphatidylcholine, including choline/ethanolamine phosphotransferase 1 (CEPT1), choline phosphotransferase 1 (CPT1), and ethanolamine phosphotransferase 1 (EPT1), were also targeted for drug-target Mendelian randomization., Results: The study found that phosphatidylcholines (OR IVW : 0.88, 95%CI: 0.80-0.96, p = 0.005) and phospholipids in medium HDL (OR IVW : 0.86, 95%CI: 0.77-0.96, p = 0.007) potentially exhibit a protective effect against sepsis nominally. However, the potential drug target of CEPT1, CPT1, and EPT1 was found to be unrelated to septic outcomes., Conclusion: Our findings suggest that increasing levels of phosphatidylcholines and medium HDL phospholipids may reduce the incidence of sepsis. This highlights the potential of lipid-based biomarkers in the diagnosis and management of sepsis, opening avenues for new therapeutic strategies., 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 Published by Elsevier Ltd.)

Background: Accurately detecting adverse pathology (AP) presence in prostate cancer patients is important for personalized clinical decision-making. Radiologists' assessment based on clinical characteristics showed poor performance for detecting AP presence., Purpose: To develop deep learning models for detecting AP presence, and to compare the performance of these models with those of a clinical model (CM) and radiologists' interpretation (RI)., Study Type: Retrospective., Population: Totally, 616 men from six institutions who underwent radical prostatectomy, were divided into a training cohort (508 patients from five institutions) and an external validation cohort (108 patients from one institution)., Field Strength/sequences: T2-weighted imaging with a turbo spin echo sequence and diffusion-weighted imaging with a single-shot echo plane-imaging sequence at 3.0 T., Assessment: The reference standard for AP was histopathological extracapsular extension, seminal vesicle invasion, or positive surgical margins. A deep learning model based on the Swin-Transformer network (TransNet) was developed for detecting AP. An integrated model was also developed, which combined TransNet signature with clinical characteristics (TransCL). The clinical characteristics included biopsy Gleason grade group, Prostate Imaging Reporting and Data System scores, prostate-specific antigen, ADC value, and the lesion maximum cross-sectional diameter., Statistical Tests: Model and radiologists' performance were assessed using area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. The Delong test was used to evaluate difference in AUC. P < 0.05 was considered significant., Results: The AUC of TransCL for detecting AP presence was 0.813 (95% CI, 0.726-0.882), which was higher than that of TransNet (0.791 [95% CI, 0.702-0.863], P = 0.429), and significantly higher than those of CM (0.749 [95% CI, 0.656-0.827]) and RI (0.664 [95% CI, 0.566-0.752])., Data Conclusion: TransNet and TransCL have potential to aid in detecting the presence of AP and some single adverse pathologic features., Level of Evidence: 4 TECHNICAL EFFICACY: Stage 4., (© 2023 International Society for Magnetic Resonance in Medicine.)

Biodetoxification fungus selectively degrades toxic inhibitors generated from pretreatment of lignocellulose without consuming fermentable sugars. However, one barrier for practical application is the sustained cell viability in the consequent fermentation step to compete the fermentable sugars with fermenting strains, resulting in sugar loss and reduced target product yield. This study investigated the competitive growth property between the biodetoxification fungus Paecilomyces variotii FN89 and the L-lactic acid bacterium Pediococcus acidilactici ZY271 under varying temperature and lactic acid osmatic stress. The results show that the L-lactic acid bacterium Ped. acidilactici ZY271 showed less thermotolerance to Pae. variotii FN89 at high temperature of 45 °C to 50 °C in both synthetic medium and wheat straw hydrolysate. In the higher temperature environment, the growth of the biodetoxification strian failed to compete with the lactic acid fermentation strain and was quickly eliminated from the fermentation system. The high temperature fermentation facilitated a fast transition from the detoxification stage to the fermentation stage for higher production of L-lactic acid., (© 2024. The Author(s).)

Leukemia caused by environmental chemical pollutants has attracted great attention, the malignant leukemic transformation model of TK6 cells induced by hydroquinone (HQ) has been previously found in our team. However, the type of leukemia corresponding to this malignant transformed cell line model needs further study and interpretation. Furthermore, the molecular mechanism of malignant proliferation of leukemic cells induced by HQ remains unclear. This study is the first to reveal the expression of aberrant genes in leukemic cells of HQ-induced malignant transformation, which may correspond to chronic lymphocytic leukemia (CLL). The expression of Linc01588, a long non-coding RNA (lncRNA), was significantly up-regulated in CLL patients and leukemic cell line model which previously described. After gain-of-function assays and loss-of-function assays, feeble cell viability, severe apoptotic phenotype and the increased secretion of TNF-α were easily observed in malignant leukemic TK6 cells with Linc01588 deletion after HQ intervention. The tumors derived from malignant TK6 cells with Linc01588 deletion inoculated subcutaneously in nude mice were smaller than controls. In CLL and its cell line model, the expression of Linc01588 and miR-9-5p, miR-9-5p and SIRT1 were negative correlation respectively in CLL and cell line model, while the expression of Linc01588 and SIRT1 were positive correlation. The dual-luciferase reporter assay showed that Linc01588 & miR-9-5p, miR-9-5p & SIRT1 could bind directly, respectively. Furthermore, knockdown of miR-9-5p successfully rescued the severe apoptotic phenotype and the increased secretion of TNF-α caused by the Linc01588 deletion, the deletion of Linc01588 in human CLL cell line MEC-2 could also inhibit malignant biological characteristics, and the phenotype caused by the deletion of Linc01588 could also be rescued after overexpression of SIRT1. Moreover, the regulation of SIRT1 expression in HQ19 cells by Linc01588 and miR-9-5 P may be related to the Akt/NF-κB pathway. In brief, Linc01588 deletion inhibits the malignant biological characteristics of HQ-induced leukemic cells via miR-9-5p/SIRT1, and it is a novel and hopeful clue for the clinical targeted therapy of CLL., 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 Authors. Published by Elsevier Inc. All rights reserved.)

Purpose To develop and validate a machine learning multimodality model based on preoperative MRI, surgical whole-slide imaging (WSI), and clinical variables for predicting prostate cancer (PCa) biochemical recurrence (BCR) following radical prostatectomy (RP). Materials and Methods In this retrospective study (September 2015 to April 2021), 363 male patients with PCa who underwent RP were divided into training ( n = 254; median age, 69 years [IQR, 64-74 years]) and testing ( n = 109; median age, 70 years [IQR, 65-75 years]) sets at a ratio of 7:3. The primary end point was biochemical recurrence-free survival. The least absolute shrinkage and selection operator Cox algorithm was applied to select independent clinical variables and construct the clinical signature. The radiomics signature and pathomics signature were constructed using preoperative MRI and surgical WSI data, respectively. A multimodality model was constructed by combining the radiomics signature, pathomics signature, and clinical signature. Using Harrell concordance index (C index), the predictive performance of the multimodality model for BCR was assessed and compared with all single-modality models, including the radiomics signature, pathomics signature, and clinical signature. Results Both radiomics and pathomics signatures achieved good performance for BCR prediction (C index: 0.742 and 0.730, respectively) on the testing cohort. The multimodality model exhibited the best predictive performance, with a C index of 0.860 on the testing set, which was significantly higher than all single-modality models (all P ≤ .01). Conclusion The multimodality model effectively predicted BCR following RP in patients with PCa and may therefore provide an emerging and accurate tool to assist postoperative individualized treatment. Keywords: MR Imaging, Urinary, Pelvis, Comparative Studies Supplemental material is available for this article . © RSNA, 2024.

Cancer is a heterogeneous disease. Although both tumor metabolism and tumor immune microenvironment are recognized as driving factors in tumorigenesis, the relationship between them is still not well-known, and potential combined targeting approaches remain to be identified. Here, we demonstrated a negative correlation between the expression of NAMPT, an NAD + metabolism enzyme, and PD-L1 expression in various cancer cell lines. A clinical study showed that a NAMPT High PD-L1 Low expression pattern predicts poor prognosis in patients with various cancers. In addition, pharmacological inhibition of NAMPT results in the transcription upregulation of PD-L1 by SIRT-mediated acetylation change of NF-κB p65, and blocking PD-L1 would induce NAMPT expression through a HIF-1-dependent glycolysis pathway. Based on these findings, we designed and synthesized a dual NAMPT/PD-L1 targeting compound, LZFPN-90, which inhibits cell growth in a NAMPT-dependent manner and blocks the cell cycle, subsequently inducing apoptosis. Under co-culture conditions, LZFPN-90 treatment contributes to the proliferation and activation of T cells and blocks the growth of cancer cells. Using mice bearing genetically manipulated tumors, we confirmed that LZFPN-90 exerted target-dependent antitumor activities, affecting metabolic processes and the immune system. In conclusion, our results demonstrate the relevance of NAD + -related metabolic processes in antitumor immunity and suggest that co-targeting NAD + metabolism and PD-L1 represents a promising therapeutic approach., (© 2024. The Author(s).)

Seven new polyketides including three chromone derivatives (1-3) and four linear ones incorporating a tetrahydrofuran ring (4-7), along with three known compounds (8-10), were obtained from the fermentation of an endophytic fungus (Chaetomium sp. UJN-EF006) isolated from the leaves of Vaccinium bracteatum. The structures of these fungal metabolites have been elucidated by spectroscopic means including MS, NMR and electronic circular dichroism. A preliminary anti-inflammatory screening with the lipopolysaccharide (LPS) induced RAW264.7 cell model revealed moderate NO production inhibitory activity for compounds 1 and 4. In addition, the expression of three LPS-induced inflammatory factors IL-6, iNOS and COX-2 was also blocked by 1 and 4., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)

Background: It is frequently observed that patients with first-ever acute ischemic stroke (AIS) have a common occurrence of asymptomatic coronary artery disease (CAD). This condition is associated with a poor prognosis. Early detection and recognition of asymptomatic CAD in first-ever AIS patients may optimize the clinical management and ultimately lead to improved outcomes. The aim of this study was to investigate the role of aortic arch plaque (AAP) detected through combined computed tomography angiography (CTA) as an early predictor of asymptomatic CAD in patients with first-ever AIS without prior diagnosis of CAD., Methods: A cross-sectional study was conducted at Xuanwu Hospital, Capital Medical University from January 2019 to December 2021, involving patients with first-ever AIS caused by large arterial atherosclerosis. Patients with a history of recognized cardiovascular disease, nonatherosclerotic arterial stenosis, atrial fibrillation related to cardioembolism, and complete carotid occlusions were excluded. The study utilized a combined coronary and cervicocephalic CTA to evaluate atherosclerosis in the cervicocephalic, aortic, and coronary arteries simultaneously. First-ever AIS patients without prior diagnosis of CAD were divided into 2 groups: 1 with asymptomatic CAD detected through CTA and the other without. Multivariate logistic regression was used to identify independent risk factors associated with the presence of asymptomatic CAD, including aortic arch, cervical and intracranial atherosclerotic characteristics (e.g., vascular stenosis, plaque thickness, extent, and complexity)., Results: Among 182 AIS patients, 84 (46.2%) had asymptomatic CAD. Increased aortic arch plaque (AAP) thickness per millimeter [adjusted odds ratio (aOR): 1.26; 95% confidence interval (CI): 1.08-1.47], presence of severe AAP (aOR: 4.24; 95% CI: 1.59-12.03), mixed AAP (aOR: 2.65; 95% CI: 1.09-6.62), and ulcerative AAP (aOR: 11.76; 95% CI: 2.05-222.84) raised the risk of asymptomatic CAD in stroke patients, independent of other factors. The combination of ulcerative AAP, diabetes mellitus, and smoking could predict asymptomatic CAD with an area under the receiver operating characteristic curve (AUC) of 0.71 (95% CI: 0.64-0.79; P<0.001). Ulcerative AAP was found to be more valuable than cervicocephalic atherosclerotic characteristics for predicting asymptomatic CAD in first-ever AIS patients., Conclusions: The presence of ulcerative AAP was associated with asymptomatic CAD in first-ever AIS patients. As an early systemic atherosclerosis feature, ulcerative AAP is probably a more valuable indicator than cervicocephalic atherosclerotic characteristics for predicting asymptomatic CAD in AIS patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1405/coif). All authors report that this research was funded by the Beijing Natural Science Foundation (No. Z190014). The authors have no other conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)