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Di Zhang,1,2 Yichong She,1,2 Jinbo Sun,1,2 Yapeng Cui,1,2 Xuejuan Yang,1,2 Xiao Zeng,1,2 Wei Qin1,2 1Engineering Research Center of Molecular and Neuro Imaging of the Ministry of Education, School of Life Science and Technology, Xidian University, Xi’an, Shaanxi, 710126, People’s Republic of China; 2Intelligent Non-Invasive Neuromodulation Technology and Transformation Joint Laboratory, Xidian University, Xi’an, People’s Republic of ChinaCorrespondence: Xiao Zeng, Xidian University, 266 Xifeng Road, Xinglong, Xi’an, Shaanxi, People’s Republic of China, 710126, Email xiaozeng1024@gmail.comPurpose: This study aims to improve brain age estimation by developing a novel deep learning model utilizing overnight electroencephalography (EEG) data.Methods: We address limitations in current brain age prediction methods by proposing a model trained and evaluated on multiple cohort data, covering a broad age range. The model employs a one-dimensional Swin Transformer to efficiently extract complex patterns from sleep EEG signals and a convolutional neural network with attentional mechanisms to summarize sleep structural features. A multi-flow learning-based framework attentively merges these two features, employing sleep structural information to direct and augment the EEG features. A post-prediction model is designed to integrate the age-related features throughout the night. Furthermore, we propose a DecadeCE loss function to address the problem of an uneven age distribution.Results: We utilized 18,767 polysomnograms (PSGs) from 13,616 subjects to develop and evaluate the proposed model. The model achieves a mean absolute error (MAE) of 4.19 and a correlation of 0.97 on the mixed-cohort test set, and an MAE of 6.18 years and a correlation of 0.78 on an independent test set. Our brain age estimation work reduced the error by more than 1 year compared to other studies that also used EEG, achieving the level of neuroimaging. The estimated brain age index demonstrated longitudinal sensitivity and exhibited a significant increase of 1.27 years in individuals with psychiatric or neurological disorders relative to healthy individuals.Conclusion: The multi-flow deep learning model proposed in this study, based on overnight EEG, represents a more accurate approach for estimating brain age. The utilization of overnight sleep EEG for the prediction of brain age is both cost-effective and adept at capturing dynamic changes. These findings demonstrate the potential of EEG in predicting brain age, presenting a noninvasive and accessible method for assessing brain aging.Keywords: brain age, sleep polysomnography, electroencephalography, deep learning, swin transformer

Shiyu Wang,1– 4 Wei Qin,1– 4 Tingting Cheng,1– 4 Cong Zeng,1– 4 Xu Chen,1– 4 Yajing Xu1– 4 1Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Changsha, Hunan, People’s Republic of China; 3Hunan Hematologic Neoplasms Clinical Medical Research Center, Changsha, Hunan, People’s Republic of China; 4National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Soochow, Jiangsu, People’s Republic of ChinaCorrespondence: Yajing Xu, Department of Hematology, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, Hunan, People’s Republic of China, Email xyyajingxu@csu.edu.cnPurpose: Acute graft-versus-host disease (aGVHD) poses a significant impediment to achieving a more favourable therapeutic outcome in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The tumour suppressor p53 plays a pivotal role in preventing aGVHD development. However, whether P53 pathway which contains p53 family members and other related genes participates in aGVHD development remains an unsolved question.Patients and Methods: Transcriptomic data was obtained from Gene Expression Omnibus (GEO) database. Gene set enrichment analysis was applied to determine the enrichment degree of signaling pathways. CIBERSORT and ssGSVA were used to evaluate immune cell compositions. Univariate and multivariate logistic regression analysis were performed to examine the independent diagnostic variables. qRT-PCR was utilized to validate the genes expression levels in our cohort.Results: A total number of 102 patients (42 aGVHD patients vs 60 non-aGVHD patients) were obtained after integrating two datasets in GEO database (GSE73809 and GSE4624). P53 pathway was remarkably suppressed in T cells from aGVHD patients and negatively associated with activated T cells as well as T cells activation related signaling pathways, including T-cell receptor (TCR), mTORC1, MYC and E2F target pathways. A risk model for aGVHD built by four genes (DDIT3, FBXW7, TPRKB and TOB1) in P53 pathway, exhibiting high differentiate and predictive value. DDIT3 and FBXW7 mRNA expression levels significantly decreased in peripheral blood mononuclear cells (PBMCs) from aGVHD patients compared with non-aGVHD group in our patient cohort, consisting with bioinformatics analysis.Conclusion: P53 pathway plays a potential role in impeding T cell activation through suppressing its related signaling pathways, thereby preventing aGVHD development. P53 pathway may emerge as a promising therapeutic target in aGVHD treatment.Keywords: allogeneic hematopoietic stem cell transplantation, aGVHD, P53 pathway, T cells, activation

Yiyue Xu,1,* Haoqian Li,1,* Xiaoqing Wang,2 Butuo Li,1 Aiqin Gao,1 Qian Zhao,1 Linlin Yang,1 Wenru Qin,1 Linlin Wang1 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 2Department of Portal Hypertension, Shandong Public Health Clinical Center, Shandong University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 JiYan Road, Jinan, 250117, People’s Republic of China, Tel +86-13793187739, Email wanglinlinatjn@163.comBackground: COVID-19 has spread worldwide, becoming a global threat to public health and can lead to complications, especially pneumonia, which can be life-threatening. However, in lung cancer patients, the prediction of pneumonia and severe pneumonia has not been studied. We aimed to develop effective models to assess pneumonia after SARS-CoV-2 infection in lung cancer patients to guide COVID-19 management.Methods: We retrospectively recruited 621 lung cancer patients diagnosed with COVID-19 via SARS-CoV-2 RT-PCR analysis in two medical centers and divided into training and validation group, respectively. Univariate and multivariate logistic regression analysis were used to identify independent risk factors of all-grade pneumonia and ≥ grade 2 pneumonia in the training group. Nomograms were established based on independent predictors and verified in the validation group. C-index, ROC curves, calibration curve, and DCA were used to evaluate the nomograms. Subgroup analyses in immunotherapy or thoracic radiotherapy patients were then conducted.Results: Among 621 lung cancer patients infected with SARS-CoV-2, 203 (32.7%) developed pneumonia, and 66 (10.6%) were ≥ grade 2. Multivariate logistic regression analysis showed that diabetes, thoracic radiotherapy, low platelet and low albumin at diagnosis of COVID-19 were significantly associated with all-grade pneumonia. The C-indices of the prediction nomograms in the training group and validation group were 0.702 and 0.673, respectively. Independent predictors of ≥ grade 2 pneumonia were age, KPS, thoracic radiotherapy, platelet and albumin at COVID 19 diagnosis, with C-indices of 0.811 and 0.799 in the training and validation groups. In the thoracic radiotherapy subgroup, 40.8% and 11% patients developed all-grade and ≥grade 2 pneumonia, respectively. The rates in the immunotherapy subgroup were 31.3% and 6.6%, respectively.Conclusion: We developed nomograms predicting the probability of pneumonia in lung cancer patients infected with SARS-CoV-2. The models showed good performance and can be used in the clinical management of COVID-19 in lung cancer patients. Higher-risk patients should be managed with enhanced protective measures and appropriate intervention.Keywords: COVID-19, pneumonia, lung cancer, risk factor, nomogram

Lini Chen,&ast; Weiyong Qin,&ast; Jiangdong Wu, Guilin Zhao, Xiaoqing Jiang, Minghui Li, Zijin Huang,&ast; Xueke Du&ast; Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zijin Huang; Xueke Du, Department of Anesthesiology, the Second Affiliated Hospital of Guangxi Medical University, No. 166 of Daxue East Road, Nanning, Guangxi, 530007, People’s Republic of China, Tel +86-13768114848 ; Tel +86-17307711159, Email batistuta921@163.com; duxueke@gxmu.edu.cnPurpose: This study aims to evaluate the effect of remimazolam on induction and maintenance of general anesthesia in kidney transplant patients.Methods: 120 patients undergoing kidney transplant were divided into two groups: Propofol group (Group P) and Remimazolam group (Group R). Anesthesia induction: remimazolam had injected IV at a dose of 0.15– 0.35 mg/kg in Group R, while propofol had injected IV at a dose of 2.0– 2.5 mg/kg in Group P. Anesthesia maintenance: remimazolam was injected IV at a dose of 0.3– 1.0 mg·kg− 1·h− 1 and propofol was injected IV at a dose of 1– 12 mg·kg− 1·h− 1 in Group R, propofol was injected IV at a dose of 3– 12 mg·kg− 1·h− 1 in Group P. All patients have the same remaining anesthesia durgs.Results: Compared with Group P, in Group R the time of disappearance of the eyelash reflex and the time to drop to 60 in BIS was longer (P < 0.05), the time of awakening was shorted (P < 0.05), the MAP of T6 was fluctuated less (P < 0.05), the incidence of hypotension and injection pain during induction was reduced (P < 0.001), the incidence of intraoperative bradycardia during operation was reduced (P < 0.05), the dosages of sedatives drug during maintenance was reduced (P < 0.05). There was no statistically significant difference in postoperative renal function between the two groups of patients (P > 0.05).Conclusion: Remimazolam can be safely and effectively used for the induction and maintenance of general anesthesia in kidney transplant patients.Keywords: remimazolam, propofol, general anesthesia, kidney transplant

Jie Liu,1,&ast; Xiajie Huang,1,&ast; Hongjie Su,1 Jie Yu,1 Xinyu Nie,1 Kaibing Liu,1 Wencong Qin,1 Yongxin Zhao,1 Yongfeng Su,1 Xiaocong Kuang,2 Di Chen,3 William W Lu,4 Yan Chen,1 Qikai Hua1 1Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Yulin Campus of Guangxi Medical University, Yulin, Guangxi, People’s Republic of China; 3Research Center for Computer-Aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 4Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong&ast;These authors contributed equally to this workCorrespondence: Yan Chen; Qikai Hua, Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email cy003@connect.hku.hk; hqk100@yeah.netPurpose: Management of severe diabetic foot ulcers (DFUs) remains challenging. Tibial cortex transverse transport (TTT) facilitates healing and limb salvage in patients with recalcitrant DFUs. However, the underlying mechanism is largely unknown, necessitating the establishment of an animal model and mechanism exploration.Methods: Severe DFUs were induced in rats, then assigned to TTT, sham, or control groups (n=16/group). The TTT group underwent a tibial corticotomy, with 6 days each of medial and lateral transport; the sham group had a corticotomy without transport. Ulcer healing was assessed through Laser Doppler, CT angiography, histology, and immunohistochemistry. Serum HIF-1α, PDGF-BB, SDF-1, and VEGF levels were measured by ELISA.Results: The TTT group showed lower percentages of wound area, higher dermis thickness (all p < 0.001 expect for p = 0.001 for TTT vs Sham at day 6) and percentage of collagen content (all p < 0.001) than the other two groups. The TTT group had higher perfusion and vessel volume in the hindlimb (all p < 0.001). The number of CD31+ cells (all p < 0.001) and VEGFR2+ cells (at day 6, TTT vs Control, p = 0.001, TTT vs Sham, p = 0.006; at day 12, TTT vs Control, p = 0.003, TTT vs Sham, p = 0.01) were higher in the TTT group. The activity of HIF-1α, PDGF-BB, and SDF-1 was increased in the TTT group (all p < 0.001 except for SDF-1 at day 12, TTT vs Sham, p = 0.005). The TTT group had higher levels of HIF-1α, PDGF-BB, SDF-1, and VEGF in serum than the other groups (all p < 0.001).Conclusion: TTT enhanced neovascularization and perfusion at the hindlimb and accelerated healing of the severe DFUs. The underlying mechanism is related to HIF-1α-induced angiogenesis.Keywords: distraction osteogenesis, tibial cortex transverse transport, diabetic foot, HIF-1α, angiogenesis

Qi Wang,1– 3,&ast; Jiaxin Dong,4,&ast; Mengxian Du,1,3,&ast; Xinna Liu,1– 3 Shiqi Zhang,1 Di Zhang,1,3 Wanyun Qin,1,3 Xikun Xu,1,2 Xianghui Li,1,3 Ruidong Su,1,2 Leyi Qiu,1,2 Baoqiang Li,4,5 Huiping Yuan1 1Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry Education, Harbin, People’s Republic of China; 3Future Medical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, People’s Republic of China; 5Laboratory of Dynamics and Extreme Characteristics of Promising Nanostructured Materials, Saint Petersburg State University, St. Petersburg, Russia&ast;These authors contributed equally to this workCorrespondence: Huiping Yuan, Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China, Email yuanhp2013@126.com Baoqiang Li, Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, 150081, People’s Republic of China, Email libq@hit.edu.cnIntroduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications.Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined.Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1β and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-β. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function.Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy. Keywords: retina, ischemia/reperfusion injury, rapamycin, carbon dots, microglial polarization, autophagy

Longbin Zheng,1,&ast; Tao Fang,2,&ast; Wei Zhang,1 Xiaojing Zhang,1 Zhiqiang Ren,1 Weimin Qin,1 Wenbo Liang,1 Qing Ma,1 Ning Yin1 1Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Anesthesiology, Xinchang County People’s Hospital, Xinchang, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Yin, Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, No. 109 Longmian Avenue, Nanjing, Jiangsu Province, 211112, People’s Republic of China, Email yinning882000@126.comPurpose: Dexmedetomidine (Dex) is a potent and highly selective α 2-adrenergic receptor agonist. Within an appropriate dose range, Dex can effectively attenuate the surgical stress response, provide intraoperative hemodynamic stability, and improve the patient recovery quality. High-dose Dex can delay patient awakening from anesthesia and increase the incidence of bradycardia. This randomized controlled trial aimed to investigate the effects of low-dose intravenous Dex premedication in patients undergoing laparoscopic cholecystectomy (LC).Material and Methods: In total, 100 patients undergoing LC were equally randomized into Group C (premedication with saline) and Group D (premedication with 0.5 μg/kg Dex). The patients were premedicated with saline or Dex, depending on the group, before anesthesia induction. Following this, anesthesia induction and endotracheal intubation was performed, and anesthesia was maintained during surgery. Following the completion of the surgery, the patients were transferred the post-anesthesia care unit (PACU) and stayed there until they met the PACU discharge criteria. The hemodynamic parameters, consumption of anesthetics, surgical duration, postoperative awakening time, extubation time, postoperative pain, and complications were recorded.Results: No significant differences were observed in the heart rate (HR) and mean arterial pressure (MAP) between the two groups before premedication (P> 0.05). The MAP and HR immediately after endotracheal intubation and immediately after extubation were significantly lower in Group D than in Group C (P< 0.05 for both). The incidence of bradycardia was significantly higher in Group D than in Group C (P< 0.05), while atropine was used in neither group. Propofol and remifentanil consumption was significantly lower in Group D than in Group C (P< 0.05). The postoperative awakening and extubation times were significantly shorter in Group D than in Group C (P< 0.05). The postoperative visual analog scale scores for pain and incidence of nausea, vomiting, and cough were significantly lower in Group D than in Group C (P< 0.05 for all).Conclusion: Our data suggest that premedication with dexmedetomidine (0.5 μg/kg) before general anesthesia induction can effectively attenuate intraoperative stress response and postoperative pain, maintain perioperative hemodynamic stability, and decrease the incidence of adverse events, which might be an effective and safe anesthetic protocol during LC worthy of further clinical application.Keywords: dexmedetomidine, laparoscopic cholecystectomy, general anesthesia, premedication

Jiemei Ye,1,2,&ast; Xiaoying Huang,3,4,&ast; Weiling Qin,1,2,&ast; Pan Liang,3,4 Jun Zhao,4 Yinxin Ye,1,2 Huojin Ji,1,2 Xinyun Peng,1,2 Yushan Liang,3,4 Yonglin Cai1,5 1Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, People’s Republic of China; 2Department of Clinical Laboratory, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, People’s Republic of China; 3Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 5Department of Preventive Medicine, Wuzhou Cancer Center, Wuzhou, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonglin Cai, Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, 543002, People’s Republic of China, Email cylzen@163.com Yushan Liang, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email yushanliang33@outlook.comPurpose: Paired Box 5 (PAX5) is a transcription factor that is widely associated with carcinogenesis. PAX5 can maintain Epstein-Barr virus (EBV) latency in B cells, while a close association exists between EBV infection and nasopharyngeal carcinoma (NPC). However, there are very few reports on the correlation between PAX5 and NPC development. The aim of this study was to investigate the role of PAX5 in NPC.Patients and Methods: The clinical value and prognostic significance of PAX5 in NPC and the association with PAX5 expression and immune cell infiltration were analyzed by multiple GEO datasets. In vivo and in vitro experiments including real-time PCR, Western blot, CCK-8 assay, and methylation sequencing were used to validate the results of bioinformatics analysis.Results: The expression of PAX5 was significantly reduced in NPC tissues, with the low expression being correlated with advanced clinical stage, low tumor mutation burden and immune activation, high relative expression of EBV, poor survival for NPC patients. PAX5 exhibited excellent diagnostic performance and had potential as a predictive factor for response to the immune checkpoint inhibitors therapy. Enrichment analysis suggested that the low expression of PAX5 was associated with the dysregulation of Hippo and Wnt signaling pathways. The promoter of PAX5 gene was hypermethylated in NPC tissues. Furthermore, the in vitro and in vivo experiments revealed that NPC tissue and cell lines had low mRNA expression levels of PAX5, the PAX5 promoter was hypermethylated in NPC cell lines, and PAX5 overexpression inhibited NPC cell proliferation and tumor growth in nude mice.Conclusion: PAX5 may be a tumor suppressor and serve as a novel potential diagnostic and prognostic marker for NPC.Keywords: nasopharyngeal carcinoma, transcription factor, PAX5, prognosis, immunity, Epstein-Barr virus

To study the behaviours of post-grouted piles installed in an uneven pebble bearing layer overlaid deep and soft soil layer in Wenzhou, China, static loading field tests of three bored post-grouted piles were conducted, considering the key design parameters of post-grouting including the grout volume, grout pressure, and bearing capacity. According to the on-site geological conditions in the region, the theoretical values were calculated through applying different calculation equations for these three parameters, and the actual values obtained from the field tests were investigated to assess the improvement effect of load-bearing performance of grouted piles installed in these geological conditions as an extremely uneven pebble-bearing layer overlaid by the deep and soft soil layer. The calculation equations of key design parameters of post-grouting in this type of soil layers were then proposed. This study could provide a reference to evaluate the performance of post-grouted piles under various grouting parameters in analogical soil layers. [ABSTRACT FROM AUTHOR]

Oxylipins derived from polyunsaturated fatty acids (PUFAs) are important endogenous signaling molecules, but are little characterized in pulmonary hypertension (PH) due to chronic obstructive pulmonary disease (COPD). In this study, we identified novel plasma oxylipins associated with PH risk in COPD patients. The plasma oxylipin profiles of COPD patients without PH (COPD-noPH) or with PH (COPD-PH) were obtained from discovery and validation cohort, using the process of LC-MS/MS analysis. There was a significant decrease in the plasma levels of both free docosahexaenoic acid (DHA) and DHA-derived oxylipins in the COPD-PH group. The multivariable logistic regression model identified DHA and four DHA-derived oxylipins (13-HDHA, 10-HDHA, 8-HDHA and 16-HDHA) exhibited significant differences between the two groups after adjusting for sex, BMI, FEV1% predicted, and smoking status. The diagnostic value of these metabolites was further evaluated through ROC curve analysis. The transcriptome profiles in peripheral blood mononuclear cells (PBMCs) of COPD-PH patients and COPD-PH patients were detected through high-throughput sequencing. The enrichment analysis revealed that the upregulated differentially expressed genes (DEGs) were highly enriched in the interferon signaling pathway. In addition, DHA supplementation proved that DHA may inhibit the development of pH by reducing the secretion of interferons derived from PBMCs. This conjecture was further confirmed by the higher level of serum interferon-γ and interferon-α2 of COPD-PH patients than that of COPD-noPH patients. The present study highlights that decreased DHA and DHA-derived oxylipins levels are suggestive of a higher risk of pH development in COPD cases., 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 UV/monochloramine (UV/NH 2 Cl) process, while efficiently eliminating micropollutants, produces toxic byproducts. This study utilized Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to investigate molecular-level changes in natural organic matter (NOM) and to disclose formation pathways of nitro(so) and chloro byproducts in the UV/NH 2 Cl process. The UV/NH 2 Cl process significantly increased the saturation and oxidation levels and altered the elemental composition of NOM. Using 15 N labeling and a screening workflow, nitro(so) byproducts with nitrogen originating from inorganic sources (i.e., reactive nitrogen species (RNS) and/or NH 2 Cl) were found to exhibit total intensities comparable to those from NOM. RNS, rather than NH 2 Cl, played a significant role in incorporating nitrogen into NOM. Through linkage analysis, nitro(so) addition emerged as an important reaction type among the 25 reaction types applied. By using phenol as a representative model compound, the nitro byproducts were confirmed to be mainly generated through the oxidation of nitroso byproducts instead of nitration. Machine learning and SHAP analysis further identified the major molecular indices distinguishing nitro(so) and chloro precursors from non-precursors. This study enhances our fundamental understanding of the mechanisms driving the generation of nitro(so) and chloro byproducts from their precursors in complex NOM during the UV/NH 2 Cl process., 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.)

Nanoplastics (<1 μm) can serve as a transport vector of environmental pollutants (e.g., heavy metals) and change their toxicities and bioavailabilities. Up to date the behaviors of adsorption and desorption heavy metals on/off nanoplastics are largely unknown. Herein, polymeric membrane potentiometric ion sensors are proposed for in-situ assessment of the real-time kinetics of heavy metal adsorption and desorption on/off nanoplastics. Results show that nanoplastics can adsorb and release heavy metals in a fast manner, indicating their superior ability in transferring heavy metals. The adsorption behaviors are closely related to the characteristics of nanoplastics and background electrolytes. Particle aggregation and increases in salinity and acidity suppress the adsorption of heavy metals on nanoplastics. The desorption efficiencies of different heavy metals are Pb 2+ (31 %) < Cu 2+ (40 %) < Cd 2+ (97 %). Our proposed method is applicable for the detection of the plastic pollutants with size <100 nm and of the samples with high salinities (e.g., seawater). This work would provide new insights into the assessment of environmental risks posed by nanoplastics and heavy metals., 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 widespread presence of microplastics and nanoplastics (MPs/NPs) in the environment has become a critical public health issue due to their potential to infiltrate and affect various biological systems. Our review is crucial as it consolidates current data and provides a comprehensive analysis of the cardiovascular impacts of MPs/NPs across species, highlighting significant implications for human health. By synthesizing findings from studies on aquatic and terrestrial organisms, including humans, this review offers insights into the ubiquity of MPs/NPs and their pathophysiological roles in cardiovascular systems. We demonstrated that exposure to MPs/NPs is linked to various cardiovascular ailments such as thrombogenesis, vascular damage, and cardiac impairments in model organisms, which likely extrapolate to humans. Our review critically evaluated methods for detecting MPs/NPs in biological tissues, assessing their toxicity, and understanding their behaviour within the vasculature. These findings emphasise the urgent need for targeted public health strategies and enhanced regulatory measures to mitigate the impacts of MP/NP pollution. Furthermore, the review underlined the necessity of advancing research methodologies to explore long-term effects and potential intergenerational consequences of MP/NP exposure. By mapping out the intricate links between environmental exposure and cardiovascular risks, our work served as a pivotal reference for future research and policymaking aimed at curbing the burgeoning threat of plastic pollution., 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.)

High-grade heavy metal elements in copper slag (CS) are worth recovering. Unfortunately, the high viscosity of leaching solution, low leaching efficiency, difficult filtration and low separation efficiency of valuable components exist in the traditional sulfuric acid leaching process. In this study, the above problems are solved by sulfuric acid pretreatment + curing + water leaching. Moreover, iron, cobalt and copper ions in solution are separated by stepwise precipitation. The final iron, cobalt, copper and silicon recoveries are 99.01 %, 98.45 %, 93.13 % and 99.52 %, respectively. Thermodynamic calculations show that H 4 SiO 4 can be converted to insoluble SiO 2 to improve filtration properties under curing conditions of sulfur dioxide partial pressures of 10 -20 ∼0 atm, oxygen partial pressures of 10 -20 ∼0 atm and 400-600k. Simulation studies of the phase equilibria of the components of the leach solution by Visual MINTEQ showed that the oxidation of Fe 2+ to Fe 3+ is necessary for the removal of Fe 2+ from the solution by precipitation. This study provides a new idea for the efficient utilization of CS., 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.)

Objectives: To explore the efficacy of diffuse magnetic resonance imaging (MRI) for identifying clinicopathological changes in immunoglobulin A nephropathy (IgAN) patients., Methods: The study enrolled IgAN patients and healthy volunteers. IgAN patients were divided into Group 1 [estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2], Group 2 (60 ≤ eGFR < 90 mL/min/1.73 m2), and Group 3 (eGFR < 60 mL/min/1.73 m2). Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and diffusion tensor imaging (DTI) were performed via 3.0 T magnetic resonance. Diffuse MRI, clinical, and pathological indicators were collected and analysed. P < .05 was considered statistically significant., Results: Forty-six IgAN patients and twenty-seven volunteers were enrolled. The apparent diffusion coefficient, diffusion coefficient (D), perfusion fraction (f), and fractional anisotropy (FA) were significantly different among IgAN subgroups and controls. These parameters were positively correlated with eGFR and negatively with creatinine, and inversely correlated with glomerular sclerosis, interstitial fibrosis, and tubular atrophy (all P < .05). They had significantly high area under the curve (AUC) for distinguishing IgAN patients from controls, while FA had the highest AUC in identifying Group 1 IgAN patients from volunteers., Conclusions: DTI and IVIM-DWI had the advantage of evaluating clinical and pathological changes in IgAN patients. DTI was superior at distinguishing early IgAN patients and might be a noninvasive marker for screening early IgAN patients from healthy individuals., Advances in Knowledge: DTI and IVIM-DWI could evaluate clinical and pathological changes and correlated with Oxford classification in IgAN patients. They could also identify IgAN patients from healthy populations, while DTI had superiority in differentiating early IgAN patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In this study, a one-step extrusion method is proposed to prepare blended polylactic acid (PLA)/thermoplastic starch (TPS) using a novel plant-derived compatibilizer, pyrogallic acid (PGA), to enhance the PLA/TPS compatibility. The effects of PGA on the mechanical behavior, fractured cross-section morphology, thermal and dynamic mechanical performance, and water resistance of PLA/TPS blends were systematically studied. Results demonstrate that the addition of PGA effectively improves the compatibility between TPS and PLA, resulting in enhanced tensile strength, crystallinity, elongation at break, thermal stability, and hydrophobicity of the blends. Specifically, incorporating 1.5 phr of PGA into the blend system yields the highest values for tensile strength (23.38 MPa) and elongation at break (16.96 %), which are 24.7 % and 233.2 %, respectively, higher than those observed for pure PLA/TPS blends. Furthermore, other properties exhibit obvious improvements upon incorporation of PGA into the blends. This approach provides a promising strategy for enhancing the performance of PLA/TPS blends and expanding their applications in food packaging, agricultural film, etc., 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.)

Recognizing the pervasive presence of alumina minerals and low-molecular-weight organic acids (LMWOAs) in the environment, this study addressed the gap in the interaction mechanisms within the ternary system involving these two components and Fe(II). Specifically, the impacts of LMWOAs on hydroxyl radicals (•OH) production and iron species transformation during Fe(II) oxidation on γ-Al 2 O 3 mineral surface were examined. Results demonstrated that adding 0.5 mM oxalate (OA) or citrate (CA) to the γ-Al 2 O 3 /Fe(II) system (28.1 μM) significantly enhanced •OH production by 1.9-fold (51.9 μM) and 1.3-fold (36.2 μM), respectively, whereas succinate (SA) exhibited limited effect (30.7 μM). Raising OA concentration to 5 mM further promoted •OH yield to 125.0 μM after 24 h. Deeper analysis revealed that CA facilitated the dissolution of adsorbed Fe(II) and its subsequent oxygenation by O 2 through both one- and two-electron transfer mechanisms, whereas OA enhanced the adsorption of dissolved Fe(II) and more efficient two-electron transfer for H 2 O 2 production. Additionally, LMWOAs presence favored the formation of iron minerals with poor crystallinity like ferrihydrite and lepidocrocite rather than well-crystallized forms such as goethite. The distinct impacts of various LMWOAs on Fe(II) oxidation and •OH generation underscore their unique roles in the redox processes at mineral surface, consequently modulating the environmental fate of prototypical pollutants like phenol., 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.)

Okra is susceptible to browning during storage. The effects of konjac glucomannan/microcapsule of thymol edible coating (TKL) on antioxidant activity and reactive oxygen (ROS) synthesis of okra during low-temperature storage were investigated. Thymol edible coating of thymol concentration 40 mg/mL (TKL40) had a regulatory effect on okra browning. After 14 days of storage, compared with the control group, the weight loss rate of TKL was reduced by 5.26 %, the hardness was increased by 24.14 %, and the L ⁎ value was increased by 31 %. Moreover, TKL40 increased the scavenging capacity of okra for DPPH and ABTS free radicals, and activated catalase and superoxide dismutase activities by promoting the accumulation of total phenolics and flavonoids. TKL40 also reduced the cell membrane damage of okra during low-temperature storage by reducing the increase of malondialdehyde and H 2 O 2 during okra storage. Meanwhile, it delayed the increase of relative conductivity and the production of O 2 .- , inhibited the activity of polyphenol oxidase in the late stage, so reduced the combination of polyphenol oxidase and phenolics to reduce the browning. Therefore, TKL40 reduces okra pericarp browning by regulating antioxidant activity and ROS synthesis., 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.)

Due to the limitations of traditional laboratory methods (TMs), identification of causative pathogens of numerous pulmonary infections (PIs) remains difficult. This study evaluated the value of metagenomic next generation sequencing (mNGS) in the identification of various respiratory pathogens. A total of 207 patients with TMs and mNGS data were collected for this retrospective study. TMs included sputum culture, blood, and bronchoalveolar lavage fluid (BALF) analysis, or polymerase chain reaction analysis of throat swabs. Otherwise, BALF was collected and analyzed using mNGS. For bacterial pathogens, sensitivities of mNGS as compared to TMs were 76.74 % and 58.14 % (P=0.012). For fungal pathogens, the detection rate of mNGS sensitivity was higher as compared to that of TMs (93.68 % vs 22.11 %; P<0.001). The positive predictive value and negative predictive value were also greater for mNGS. Use of mNGS for BALF analysis offers good specificity and thus facilitates to the clinical diagnosis of PIs., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Peony seed is an excellent oil crop, and peony seed oil is rich in unsaturated fatty acids needed by the human body. In this study, inductively coupled plasma mass spectrometry (ICP-MS), fingerprint, and chemometrics, the correlation between the content of inorganic elements in oil peony seeds, their origins, and varieties were investigated. Meanwhile, estimated daily intake (EDI), target hazard quotient (THQ), hazard index (HI), and carcinogenic risks (CR) were combined to evaluate the comprehensive health risks of heavy metals in peony seed oil. The results showed that the difference in the content of inorganic elements could identify the varieties of oil peony seeds. Sr, K, Ca, V, Al, Fe, Cu, Ba, As, Ga, Co, and Rb were the characteristic inorganic elements that played a role in identification. In addition, The THQs and HIs (< 1) for non-carcinogenic elements indicated no risk. The CRs indicated that the carcinogenic harm was negligible. The study concluded that three varieties of peony seed oil would not pose any health hazard. It provided an effective comprehensive method for the identification of oil peony seeds and predicted the potential health risks of edible peony seed oil, providing a reference for the development and consumption of peony seed oil food., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ammonia (NH 3 ) in exhaled breath (EB) has been a biomarker for kidney function, and accurate measurement of NH 3 is essential for early screening of kidney disease. In this work, we report an optical sensor that combines ultraviolet differential optical absorption spectroscopy (UV-DOAS) and spectral reconstruction fitting neural network (SRFNN) for detecting NH 3 in EB. UV-DOAS is introduced to eliminate interference from slow change absorption in the EB spectrum while spectral reconstruction fitting is proposed for the first time to map the original spectra onto the sine function spectra by the principle of least absolute deviations. The sine function spectra are then fitted by the least-squares method to eliminate noise signals and the interference of exhaled nitric oxide. Finally, the neural network is built to enable the detection of NH 3 in EB at parts per billion (ppb) level. The laboratory results show that the detection range is 9.50-12425.82 ppb, the mean absolute percentage error (MAPE) is 0.83%, and the detection accuracy is 0.42%. Experimental results prove that the sensor can detect breath NH 3 and identify EB in simulated patients and healthy people. Our sensor will serve as a new and effective system for detecting breath NH 3 with high accuracy and stability in the medical field.

Currently, inhomogeneous distribution of Zn 2+ on the surface of the Zn anode is still the essential reason for dendrite formation and unsatisfactory stability of zinc ion batteries. Given the merits of strong interaction between Sn and Zn, as well as a low nucleation barrier during Zn deposition, the combination of metallic Sn with carbon material is expected to improve the deposition of zinc ions and inhibit the growth of zinc dendrites by guiding the homogeneous plating/stripping of zinc on the electrode surface. In this article, zincophilic Sn nanoparticles with low nucleation barriers and strong interaction with Zn 2+ were embedded into 3D N-doped carbon nanofibers using a simple electrostatic spinning technique. Accordingly, when serving as an artificial coating layer for the zinc metal anode, an ultrastable Sn@NCNFs@Zn||Sn@NCNFs@Zn symmetric cell can be achieved for over 3500 h with a low nucleation overpotential of 29.1 mV. Significantly, the full cell device assembled with the as-prepared anode and MnO 2 cathode exhibits desirable electrochemical behaviors. Moreover, this simple method could be extended to other metal-carbon composites, and to ensure ease in scaling up as required. Such significant approach can provide an effective strategy for the design of high-performance zinc anodes.

Signal Recognition Particle 54 kDa (SRP54) is a subunit of the signal recognition particle (SRP), a cytoplasmic ribonucleoprotein complex guiding the transportation of newly synthesized proteins from polyribosomes to endoplasmic reticulum. In mammals, it has been reported to regulate the RLR signaling pathway negatively by impairing the association between MAVS and MDA5/RIG-I. However, the role of SRP54 in teleost antiviral innate immune response remains obscure. In this study, the SRP54 homolog of black carp (bcSRP54) has been cloned, and its function in antiviral innate immunity has been elucidated. The CDS of bcSRP54 gene consists of 1515 nucleotides and encodes 504 amino acids. Immunofluorescence (IF) showed that bcSRP54 was mainly distributed in the cytoplasm. Overexpressed bcSRP54 significantly reduced bcMDA5-mediated transcription of interferon (IFN) promoter in reporter assay. Co-expression of bcSRP54 and bcMDA5 significantly suppressed bcMDA5-mediated IFN signaling and antiviral activity, while bcSRP54 knockdown increased the antiviral ability of host cells. In addition, the results of the immunofluorescence staining demonstrated the subcellular overlapping between bcSRP54 and bcMDA5, and the co-immunoprecipitation (co-IP) experiment identified their association. Furthermore, the over-expression of bcSRP54 did not influence the protein expression and ubiquitination modification level of bcMDA5, however, hindered the binding of bcMDA5 to bcMAVS. In summary, our results conclude that bcSRP54 targets bcMDA5 and inhibits the interaction between bcMDA5 and MAVS, thereby negatively regulating antiviral innate immunity, which provides insight into how teleost SRP54 regulates IFN signaling., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

The escalating levels of plastic waste and energy crises underscore the urgent need for effective waste-to-energy strategies. This study focused on converting polypropylene wastes into high-value products employing various iron-based catalysts and microwave radiative thermal processing. The Al-Fe catalysts exhibited exceptional performance, achieving a hydrogen utilization efficiency of 97.65% and a yield of 44.07 mmol/g PP. The gas yields increased from 19.99 to 94.21 wt % compared to noncatalytic experiments. Furthermore, this catalytic system produced high-value bamboo-shaped carbon nanotubes that were absent in other catalysts. The mechanism analysis on catalytic properties and product yields highlighted the significance of oxygen vacancies in selecting high-value products through two adsorption pathways. Moreover, the investigation examined the variations in product distribution mechanisms between conventional and microwave pyrolysis, in which microwave conditions resulted in 4 times higher hydrogen yields. The technoeconomic assessment and Monte Carlo risk analysis further compared the disparity. The microwave technique had a remarkable internal rate of return (IRR) of 39%, leading to an income of $577/t of plastic with a short payback period of 2.5 years. This research offered sustainable solutions for the plastic crisis, validating the potential applicability of commercializing the research outcomes in real-world scenarios.

Tacrolimus (TAC) has high pharmacokinetic (PK) variability during the early transplantation period. The relationships between whole-blood and intracellular TAC concentrations and clinical outcomes remain controversial. This study identifies the factors affecting the PK variability of TAC and characterizes the relationships between whole-blood and intracellular TAC concentrations. Data regarding whole-blood TAC concentrations of 1,787 samples from 215 renal transplant recipients (<90 days postoperative) across two centers and intracellular TAC concentrations (648 samples) digitized from previous studies were analyzed using nonlinear mixed-effects modeling. The effects of potential covariates were screened, and the distribution of whole-blood to intracellular TAC concentration ratios (R WB:IC ) was estimated. The final model was evaluated using bootstrap, goodness of fit, and prediction-corrected visual predictive checks. The optimal dosing regimens and target ranges for each type of immune cell subsets were determined using Monte Carlo simulations. A two-compartment model adequately described the data, and the estimated mean TAC CL/F was 23.6 L·h -1 (relative standard error: 11.5 %). The hematocrit level, CYP3A5*3 carrier status, co-administration with Wuzhi capsules, and tapering prednisolone dose may contribute to the high variability of TAC PK variability during the early post-transplant period. The estimated R WB:IC of all TAC concentrations in peripheral blood mononuclear cells (PBMCs) was 4940, and inter-center variability of PBMCs was observed. The simulated TAC target range in PBMCs was 20.2-85.9 pg·million cells -1 . Inter-center variability in intracellular concentrations should be taken into account in further analyses. TAC dosage adjustments can be guided based on PK/PD variability and simulated intracellular concentrations., 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 inherent chiral structures of DNA serve as attractive scaffolds to construct DNA hybrid catalysts for valuable enantioselective transformations. Duplex and G-quadruplex DNA-based enantioselective catalysis has made great progress, yet novel design strategies of DNA hybrid catalysts are highly demanding and atomistic analysis of active centers is still challenging. DNA i-motif structures could be finely tuned by different cytosine-cytosine base pairs, providing a new platform to design DNA catalysts. Herein, we found that a human telomeric i-motif DNA containing cytosine-silver(I)-cytosine (C-Ag + -C) base pairs interacting with Cu(II) ions (i-motif DNA(Ag + )/Cu 2+ ) could catalyze Diels-Alder reactions with full conversions and up to 95 % enantiomeric excess. As characterized by various physicochemical techniques, the presence of Ag + is proved to replace the protons in hemiprotonated cytosine-cytosine (C : C + ) base pairs and stabilize the DNA i-motif to allow the acceptance of Cu(II) ions. The i-motif DNA(Ag + )/Cu 2+ catalyst shows about 8-fold rate acceleration compared with DNA and Cu 2+ . Based on DNA mutation experiments, thermodynamic studies and density function theory calculations, the catalytic center of Cu(II) ion is proposed to be located in a specific loop region via binding to one nitrogen-7 atom of an unpaired adenine and two phosphate-oxygen atoms from nearby deoxythymidine monophosphate and deoxyadenosine monophosphate, respectively., (© 2024 Wiley-VCH GmbH.)

Purpose: Early evaluation of tumor heterogeneity related to metastasis and outcomes is a major challenge in the management of advanced breast cancer (BCa) in the clinic. In this study, we introduced the value of baseline circulating tumor cells (CTC) and ctDNA for early differentiation of clinical stages, tumor heterogeneity, and prognosis in clinic., Experimental Design: A total of 292 patients with BCa were enrolled in this study, including 254 Stage IV and 38 Stage III patients, and examined the baseline levels of CTCs, CTC-clusters, and plasma ctDNA before initiating therapies. Outcomes including progression-free survival (PFS) and overall survival were evaluated using proportional hazards regression analysis., Results: The baseline CTCs, including HER2+ CTCs, in Stage IV patients were approximately 9.5 times higher than those detected in Stage III patients. Baseline CTC counts with a cutoff of 5 were significantly associated with the prognosis. Within each stage, patients with <5 CTCs had significantly longer PFS. Stage III patients with no CTCs exhibited the longest survival compared with patients with ≥1 CTC. CTC-clusters were only found in Stage IV patients, among whom 15 Stage IV patients with ≥5 CTC-clusters had the worst PFS compared with the 239 Stage IV patients with <5 CTC-clusters. Similar outcomes were observed in 28 out of 254 Stage IV patients who had at least one CTC-cluster detected, as these patients had shorter PFS compared with CTC-cluster negative group. The major differences in ctDNA mutations between patients with Stage III and Stage IV BCa were in PIK3CA and ESR1, which were associated with specific organ metastasis and worse outcomes., Conclusions: Assessing the baseline levels of CTCs, CTC-clusters, and mutational ctDNA profile could reliably aid in differentiation of clinical stage and early prediction of metastasis and outcomes in advanced BCa., (©2024 American Association for Cancer Research.)

Alteration of cell metabolism is one of the essential characteristics of tumor growth. Cancer stem cells (CSCs) are the initiating cells of tumorigenesis, proliferation, recurrence, and other processes, and play an important role in therapeutic resistance and metastasis. Thus, identification of the metabolic profiles in prostate cancer stem cells (PCSCs) is critical to understanding prostate cancer progression. Using untargeted metabolomics and lipidomics methods, we show distinct metabolic differences between prostate cancer cells and PCSCs. Urea cycle is the most significantly altered metabolic pathway in PCSCs, the key metabolites arginine and proline are evidently elevated. Proline promotes cancer stem-like characteristics via the JAK2/STAT3 signaling pathway. Meanwhile, the enzyme pyrroline-5-carboxylate reductase 1 (PYCR1), which catalyzes the conversion of pyrroline-5-carboxylic acid to proline, is highly expressed in PCSCs, and the inhibition of PYCR1 suppresses the stem-like characteristics of prostate cancer cells and tumor growth. In addition, carnitine and free fatty acid levels are significantly increased, indicating reprogramming of fatty acid metabolism in PCSCs. Reduced sphingolipid levels and increased triglyceride levels are also observed. Collectively, our data illustrate the comprehensive landscape of the metabolic reprogramming of PCSCs and provide potential therapeutic strategies for prostate cancer., (© 2024 UICC.)

The human brain is organized as a complex, hierarchical network. However, the structural covariance patterns among brain regions and the underlying biological substrates of such covariance networks remain to be clarified. The present study proposed a novel individualized structural covariance network termed voxel-based texture similarity networks (vTSNs) based on 76 refined voxel-based textural features derived from structural magnetic resonance images. Validated in three independent longitudinal healthy cohorts (40, 23, and 60 healthy participants, respectively) with two common brain atlases, we found that the vTSN could robustly resolve inter-subject variability with high test-retest reliability. In contrast to the regional-based texture similarity networks (rTSNs) that calculate radiomic features based on region-of-interest information, vTSNs had higher inter- and intra-subject variability ratios and test-retest reliability in connectivity strength and network topological properties. Moreover, the Spearman correlation indicated a stronger association of the gene expression similarity network (GESN) with vTSNs than with rTSNs (vTSN: r = 0.600, rTSN: r = 0.433, z = 39.784, P < 0.001). Hierarchical clustering identified 3 vTSN subnets with differential association patterns with 13 coexpression modules, 16 neurotransmitters, 7 electrophysiology, 4 metabolism, and 2 large-scale structural and 4 functional organization maps. Moreover, these subnets had unique biological hierarchical organization from the subcortex-limbic system to the ventral neocortex and then to the dorsal neocortex. Based on 424 unrelated, qualified healthy subjects from the Human Connectome Project, we found that vTSNs could sensitively represent sex differences, especially for connections in the subcortex-limbic system and between the subcortex-limbic system and the ventral neocortex. Moreover, a multivariate variance component model revealed that vTSNs could explain a significant proportion of inter-subject behavioral variance in cognition (80.0 %) and motor functions (63.4 %). Finally, using 494 healthy adults (aged 19-80 years old) from the Southwest University Adult Lifespan Dataset, the Spearman correlation identified a significant association between aging and vTSN strength, especially within the subcortex-limbic system and between the subcortex-limbic system and the dorsal neocortex. In summary, our proposed vTSN is robust in uncovering individual variability and neurobiological brain processes, which can serve as biologically plausible measures for linking biological processes and human behavior., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Lead (Pb) and cadmium (Cd) have been identified as the primary contaminants in soil, posing potential health threats. This study aimed to examine the effects of applying a nitrogen fertilizer and a fungal agent Trichoderma harzianum J2 (nitrogen alone, fungi alone, and combined use) on the phytoremediation of soils co-contaminated with Pb and Cd. The growth of Leucaena leucocephala was monitored in the seedling, differentiation, and maturity stages to fully comprehend the remediation mechanisms. In the maturity stage, the biomass of L. leucocephala significantly increased by 18% and 29% under nitrogen-alone (NCK + ) and fungal agent-alone treatments (J2), respectively, compared with the control in contaminated soil (CK + ). The remediation factors of Pb and Cd with NCK + treatment significantly increased by 50% and 125%, respectively, while those with J2 treatment increased by 73% and 145%, respectively. The partial least squares path model suggested that the nitrogen-related soil properties were prominent factors affecting phytoextraction compared with biotic factors (microbial diversity and plant growth). This model explained 2.56 of the variation in Cd concentration under J2 treatment, and 2.97 and 2.82 of the variation in Pb concentration under NCK + and J2 treatments, respectively. The redundancy analysis showed that the samples under NCK + and J2 treatments were clustered similarly in all growth stages. Also, Chytridiomycota, Mucoromucota, and Ciliophora were the key bioindicators for coping with heavy metals. Overall, a similar remediation mechanism allowed T. harzianum J2 to replace the nitrogen fertilizer to avoid secondary pollution. In addition, their combined use further increased the remediation efficiency., 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: Hepatic arterial infusion chemotherapy (HAIC) has shown satisfactory therapeutic efficacy in unresectable hepatocellular carcinoma (HCC) and is regarded as an important conversion treatment. However, limited information is available regarding the optimal timing of HAIC-based conversion hepatectomy. This study aims to determine the optimal timing for HAIC-based conversion surgery in patients with HCC., Methods: Data from a retrospective cohort of patients who underwent HAIC-based conversion hepatectomy were reviewed. Oncological outcomes, surgical information, and risk factors were comparatively analyzed., Results: In total, 424 patients with HCC who underwent HAIC-based conversion hepatectomy were included and were divided into responder (n=312) and nonresponder (n=112) groups. The overall survival (OS) and recurrence-free survival (RFS) rates of both the whole responder cohort and patients who achieved a response after 4-6 cycles of HAIC were significantly better than those of the nonresponder cohort. Higher OS and RFS were observed in responders than in nonresponders with advanced-stage HCC. Patients in the responder group had a shorter occlusion duration and less intraoperative blood loss than those in the nonresponder group. There were no significant differences in other surgical information or postoperative complications between the two groups. Tumor response, differentiation, postoperative alpha-fetoprotein level, postoperative protein induced by vitamin K absence or antagonist-II level, age, microvascular invasion, pre-HAIC neutrophil-to-lymphocyte ratio, and preoperative systemic inflammatory response index were independent risk factors for poor long-term survival., Conclusions: Conversion surgery should be considered when tumor response is achieved. Our findings may be useful in guiding surgeons and patients in decision-making regarding HAIC-based conversion hepatectomy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Herein, we presented an enantioselective intramolecular Diels-Alder (IMDA) reaction with vinyl branched vinylidene ortho -quinone methide (VQM). The control of site selectivity in the IMDA reaction led to both chiral bridged bicyclo[4.3.1] and [5.3.1] architectures with high isolated yields (up to 85%) and excellent enantioselectivities (up to 97% ee).

Prostate cancer (PCa) rarely responds to immune-checkpoint blockade (ICB) therapies. Cancer-associated fibroblasts (CAFs) are critical components of the immunologically "cold" tumor microenvironment and are considered a promising target to enhance the immunotherapy response. In this study, we aimed to reveal the mechanisms regulating CAF plasticity to identify potential strategies to switch CAFs from pro-tumorigenic to anti-tumor phenotypes and enhance ICB efficacy in PCa. Integration of four PCa single-cell RNA-sequencing datasets defined pro-tumorigenic and anti-tumor CAFs, and RNA-seq, flow cytometry, and a PCa organoid model demonstrated the functions of two CAF subtypes. Extracellular matrix-associated CAFs (ECM-CAF) promoted collagen deposition and cancer cell progression, and lymphocyte-associated CAFs (Lym-CAF) exhibited an anti-tumor phenotype and induced the infiltration and activation of CD8+ T cells. YAP1 activity regulated the ECM-CAF phenotype, and YAP1 silencing promoted switching to Lym-CAFs. NF-κB p65 was the core transcription factor in the Lym-CAF subset, and YAP1 inhibited nuclear translocation of p65. Selective depletion of YAP1 in ECM-CAFs in vivo promoted CD8+ T-cell infiltration and activation and enhanced the therapeutic effects of anti- PD-1 treatment in PCa. Overall, this study revealed a mechanism regulating CAF identity in PCa and highlighted a therapeutic strategy for altering the CAF subtype to suppress tumor growth and increase sensitivity to ICB.

Background: Induction chemotherapy of docetaxel plus cisplatin (TP) is myelosuppressive, leading to severe neutropenia and febrile neutropenia (FN). Herein, we aimed to investigate the efficacy and safety of mecapegfilgrastim in the prevention of neutropenia in patients with locally advanced nasopharyngeal carcinoma who received the TP regimen., Methods: A total of 30 treatment-naive patients with locally advanced nasopharyngeal carcinoma were included in this study. Mecapegfilgrastim 6 mg was injected 24-48 h after the completion of induction chemotherapy with the TP regimen., Results: The incidence of grade ≥3 neutropenia during the three induction chemotherapy cycles was 6.7% (95% CI, 0.8%-22.1%). In the first cycle of chemotherapy, the incidence of grade ≥3 neutropenia was 3.3% (95% CI, 0.1%-17.2%). No FN or antibiotic usage was reported. All 30 patients completed the induction chemotherapy cycles., Conclusion: Mecapegfilgrastim effectively reduced the incidence of chemotherapy-induced neutropenia and FN in patients with locally advanced nasopharyngeal carcinoma., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Climate change presents formidable challenges to forest biodiversity and carbon storage. Bamboo forests will be affected particularly in Southwest China's mountainous regions. Bamboo serves as not only a key food resource and habitat for giant panda Ailuropoda melanoleuca but also a potential carbon sink due to its rapid energy-to-matter conversion capability. We employ the MaxEnt model to project the distribution shifts of 20 giant panda foraged bamboo species in Sichuan Province under future climate scenarios, utilizing climate data of 30m resolution. Based on the changes in the diversity and distribution area of bamboo communities caused by climate change, the changing of giant pandas' food resources and the carbon storage of bamboo forests were calculated. The results indicated that the area of bamboo communities is projected to expand by 17.94%-60.88% more than now by the end of the 21st century. We analyzed the energy balance between the dietary needs of giant pandas and the energy provided by bamboo. We predicted that bamboo communities from 2000 to 2150 could support the continuous growth of the giant panda population (6533 wild individuals by 2140-2150 in an ideal state in Sichuan province). However, the species diversity and carbon storage of bamboo forests face out-of-sync fluctuations, both temporally and spatially. This is a critical issue for subalpine forest ecosystem management under climate change. Therefore, we propose a dynamic conservation management framework for giant panda habitats across spatial and temporal scales. This framework aims to facilitate the adaptation of subalpine forest ecosystems to climate change. This innovative approach, which integrates climate change into the conservation strategy for endangered species, contributes a conservation perspective to global climate action, highlighting the interconnectedness of biodiversity preservation and climate mitigation., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, author-ship, and/or publication of this article., (Copyright © 2024. Published by Elsevier Ltd.)

This paper summarizes the colonization dynamics of biofilms on microplastics (MPs) surfaces in aquatic environments, encompassing bacterial characteristics, environmental factors affecting biofilm formation, and matrix types and characteristics. The interaction between biofilm and MPs was also discussed. Through summarizing recent literatures, it was found that MPs surfaces offer numerous benefits to microorganisms, including nutrient enrichment and enhanced resistance to environmental stress. Biofilm colonization changes the surface physical and chemical properties as well as the transport behavior of MPs. At the same time, biofilms also play an important role in the fragmentation and degradation of MPs. In addition, we also investigated the coexistence level, adsorption mechanism, enrichment, and transformation of MPs by environmental pollutants mediated by biofilms. Moreover, an interesting aspect about the colonization of biofilms was discussed. Biofilm colonization not only had a great effect on the accumulation of heavy metals by MPs, but also affects the interaction between particles and environmental pollutants, thereby changing their toxic effects and increasing the difficulty of MPs treatment. Consequently, further attention and research are warranted to delve into the internal mechanisms, environmental risks, and the control of the coexistence of MPs and biofilms., 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.)

Materials with multifunctionality affect society enormously. However, the inability to surmount multiple functionality trade-offs limits the discovery of next-generation multifunctional materials. Departing from conventional alloying design philosophy, we present a hierarchical nanostructure (HNS) strategy to simultaneously break multiple performance trade-offs in a material. Using a praseodymium-cobalt (PrCo 5 ) ferromagnet as a proof of concept, the resulting HNS outperforms contemporary high-temperature ferromagnets with a 50 to 138% increase in electrical resistivity while achieving their highest energy density. Our strategy also enables an exceptional thermal stability of coercivity (-0.148%/°C)-a key characteristic for device accuracy and reliability-surpassing that of existing commercial rare-earth magnets. The multifunctionality stems from the deliberately introduced nanohierarchical structure, which activates multiple micromechanisms to resist domain wall movement and electron transport, offering an advanced design concept for multifunctional materials.

Single-ion conductors based on covalent organic frameworks (COFs) have garnered attention as a potential alternative to currently prevalent inorganic ion conductors owing to their structural uniqueness and chemical versatility. However, the sluggish Li + conduction has hindered their practical applications. Here, we present a class of solvent-free COF single-ion conductors (Li-COF@P) based on weak ion-dipole interaction as opposed to traditional strong ion-ion interaction. The ion (Li + from the COF)-dipole (oxygen from poly(ethylene glycol) diacrylate embedded in the COF pores) interaction in the Li-COF@P promotes ion dissociation and Li + migration via directional ionic channels. Driven by this single-ion transport behavior, the Li-COF@P enables reversible Li plating/stripping on Li-metal electrodes and stable cycling performance (88.3% after 2000 cycles) in organic batteries (Li metal anode||5,5'-dimethyl-2,2'-bis-p-benzoquinone (Me 2 BBQ) cathode) under ambient operating conditions, highlighting the electrochemical viability of the Li-COF@P for all-solid-state organic batteries., (© 2024. The Author(s).)

Objectives: Depressive symptoms are the most prevalent comorbidity in individuals with obsessive-compulsive disorder (OCD). The objective of this study was to investigate the dynamic characteristics of resting-state neural activities in OCD patients with depressive symptoms., Methods: We recruited 29 OCD patients with depressive symptoms, 21 OCD patients without depressive symptoms, and 27 healthy controls, and collected data via structural and functional magnetic resonance imaging (fMRI). We analyzed the fMRI results using the dynamic amplitude of low-frequency fluctuation (dALFF) and support vector machine (SVM) techniques., Results: Compared with OCD patients without depressive symptoms, OCD patients with depressive symptoms exhibited an increased dALFF in the left precuneus and decreased dALFF in the right medial frontal gyrus. The SVM indicated that the integration of aberrant dALFF values in the left precuneus and right medial frontal gyrus led to an overall accuracy of 80%, a sensitivity of 79%, and a specificity of 100% in detecting depressive symptoms among OCD patients., Conclusion: Therefore, our study reveals that OCD patients with depressive symptoms display neural activities with unique dynamic characteristics in the resting state. Accordingly, abnormal dALFF values in the left precuneus and right medial frontal gyrus could be used to identify depressive symptoms in OCD 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 Shang, Chen, Ding, Qin, Li, Wei, Ding, Yang, Qi, Qin, Lv, Li, Pan, Zhan, Xiao, Sun, Wang, Yu, Li and Li.)

Induced arterial pressure oscillation may improve the assessment of dynamic cerebral autoregulation (dCA) based on transfer function analysis (TFA). This study investigated dCA during repeated handgrip exercise (RHE) and compared it to spontaneous rest and sit-stand maneuvers (SSMs) which are often used for dCA assessment. After a 5-minute rest, 20 healthy young adults (10 women) underwent 5 minutes of RHE and SSMs at 0.05 Hz and 0.10 Hz in random order. Power spectral densities (PSDs) and TFA gain, phase, and coherence of mean arterial pressure (MAP) and blood velocity in the middle cerebral artery (MCAv mean ) were compared in very low (VLF: 0.02-0.07 Hz) and low (LF: 0.07-0.20 Hz) frequencies. End-tidal CO 2 (EtCO 2 ) was recorded throughout the study. Compared with rest, RHE increased PSDs of MAP and MCAv mean in VLF (444% and 273% respectively) and LF (1571% and 1765% respectively), with significant elevations in TFA coherence (VLF: 131%, LF: 128%), while SSMs exhibited the highest PSD and coherence values (all P < 0.05). TFA gains and phases were similar between RHE and rest, but VLF gain was higher while VLF and LF phases were lower during SSMs than RHE (all P < 0.05). EtCO 2 was higher during SSMs than rest and RHE (both P < 0.05), with the individual changes positively correlated with VLF gain changes (R 2 = 0.289, P < 0.001). These results suggest that RHE significantly increases arterial pressure oscillation and TFA coherence and may improve the dCA assessment in individuals not capable of performing repeated postural changes.

Ammonia-oxidizing archaea (AOA) are widely distributed in marine and terrestrial habitats, contributing significantly to global nitrogen and carbon cycles. However, their genomic diversity, ecological niches, and metabolic potentials in the anoxic intertidal aquifers remain poorly understood. Here, we discovered and named a novel AOA genus, Candidatus Nitrosomaritimum, from the intertidal aquifers of Yancheng Wetland, showing close metagenomic abundance to the previously acknowledged dominant Nitrosopumilus AOA. Further construction of ammonia monooxygenase-based phylogeny demonstrated the widespread distribution of Nitrosomaritimum AOA in global estuarine-coastal niches and marine sediment. Niche differentiation among sublineages of this new genus in anoxic intertidal aquifers is driven by salinity and dissolved oxygen gradients. Comparative genomics revealed that Candidatus Nitrosomaritimum has the genetic capacity to utilize urea and possesses high-affinity phosphate transporter systems ( phnCDE ) for surviving phosphorus-limited conditions. Additionally, it contains putative nosZ genes encoding nitrous-oxide (N 2 O) reductase for reducing N 2 O to nitrogen gas. Furthermore, we gained first genomic insights into the archaeal phylum Hydrothermarchaeota populations residing in intertidal aquifers and revealed their potential hydroxylamine-detoxification mutualism with AOA through utilizing the AOA-released extracellular hydroxylamine using hydroxylamine oxidoreductase. Together, this study unravels the overlooked role of priorly unknown but abundant AOA lineages of the newly discovered genus Candidatus Nitrosomaritimum in biological nitrogen transformation and their potential for nitrogen pollution mitigation in coastal environments.

Objectives: Cerebral arteriovenous malformations (AVMs) present complex neurovascular challenges, characterized by direct arteriovenous connections that disrupt normal brain blood flow dynamics. Traditional lumped parameter models (LPMs) offer a simplified angioarchitectural representation of AVMs, yet often fail to capture the intricate structure within the AVM nidus. This research aims at refining our understanding of AVM hemodynamics through the development of patient-specific LPMs utilizing three-dimensional (3D) medical imaging data for enhanced structural fidelity., Methods: This study commenced with the meticulous delineation of AVM vascular architecture using threshold segmentation and skeletonization techniques. The AVM nidus's core structure was outlined, facilitating the extraction of vessel connections and the formation of a detailed fistulous vascular tree model. Sampling points, spatially distributed and derived from the pixel intensity in imaging data, guided the construction of a complex plexiform tree within the nidus by generating smaller Y-shaped vascular formations. This model was then integrated with an electrical analog model to enable precise numerical simulations of cerebral hemodynamics with AVMs., Results: The study successfully generated two distinct patient-specific AVM networks, mirroring the unique structural and morphological characteristics of the AVMs as captured in medical imaging. The models effectively represented the intricate fistulous and plexiform vessel structures within the nidus. Numerical analysis of these models revealed that AVMs induce a blood shunt effect, thereby diminishing blood perfusion to adjacent brain tissues., Conclusion: This investigation enhances the theoretical framework for AVM research by constructing patient-specific LPMs that accurately reflect the true vascular structures of AVMs. These models offer profound insights into the hemodynamic behaviors of AVMs, including their impact on cerebral circulation and the blood steal phenomenon. Further incorporation of clinical data into these models holds the promise of deepening the theoretical comprehension of AVMs and fostering advancements in the diagnosis and treatment of AVMs., Competing Interests: Declaration of competing interest The authors would like to declare on behalf of the co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. No conflict of interest exists in the submission of this manuscript, and the manuscript is approved by all authors for publication., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Recent studies have shown that the gut microbiota (GM), immune cells, and coronary heart disease (CHD) are closely related, but the causal nature of these relationships is largely unknown. This study aimed to investigate this causal relationship and reveal the effect of GM and immune cells on the risk of developing CHD using mediated Mendelian randomization (MR) analysis., Methods: First, we searched for data related to GM, immune cells, and CHD through published genome-wide association studies (GWAS). We filtered the single nucleotide polymorphisms (SNPs) associated with GM and immune cells and then performed the first MR analysis to identify disease-associated intestinal bacteria and disease-associated immune cells. Subsequently, three MR analyses were conducted: from disease-associated GM to disease-associated immune cells, from disease-associated immune cells to CHD, and from disease-associated GM to CHD. Each MR analysis was conducted using inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted models, and simple models., Results: A total of six GM and 25 immune cells were found to be associated with CHD. In the MR analysis using the inverse variance weighting (IVW) method, g&#95;&#95;Desulfovibrio.s&#95;&#95;Desulfovibrio&#95;piger was associated with EM DN (CD4-CD8-) %T cells ( P < 0.05 and OR > 1), EM DN (CD4-CD8-) %T cells was associated with CHD ( P < 0.05 and OR < 1), and g&#95;&#95;Desulfovibrio.s&#95;&#95;Desulfovibrio&#95;piger was associated with CHD ( P < 0.05 and OR < 1)., Conclusion: An increase in the abundance of g&#95;&#95;Desulfovibrio.s&#95;&#95;Desulfovibrio&#95;piger leads to an increase in the amount of EM DN (CD4-CD8-) %T cells, and an increase in the amount of EM DN (CD4-CD8-) %T cells reduces the risk of developing CHD. Our study provides some references for reducing the incidence of CHD by regulating GM and immune cells., 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 Yang, Song, Tang, Liu, Zhu, Ouyang, Zhang, He and Qin.)

The asymmetric synthesis of thiophene-derived compounds, including catalytic asymmetric dearomatization of thiophene and atroposelective synthesis of benzothiophene derivatives, has rarely been reported. In this work, the asymmetric transformation of the thiophene motif is investigated. Through the rational design of substrates with a thiophene structure, by using the vinylidene ortho -quinone methide (VQM) intermediate as a versatile tool, axially chiral naphthyl-benzothiophene derivatives and thiophene-dearomatized chiral spiranes were obtained in high yields with excellent enantioselectivities., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Pyroglutamate (pE)-modified amyloid-β (Aβ) peptides play a crucial role in the development of Alzheimer's disease. pEAβ 3-42 can rapidly form oligomers that gradually elongate hydrophobic segments to form β-sheet-rich amyloid intermediates, ultimately resulting in the formation of mature amyloid fibrils. pEAβ 3-42 can also catalyze the aggregation of Aβ species and subsequently accelerate the formation of amyloid senile plaques. Considering the recent clinical success of the pEAβ 3-42 -targeting antibody donanemab, molecules that strongly bind pEAβ 3-42 and prevent its aggregation and catalytic effect on Aβs may also provide potential therapeutic options for Alzheimer's disease. Here, we demonstrate that the natural antibiotic cyclopeptide tyrocidine A (TA) not only strongly inhibits the aggregation of Aβ 1-42 as previously reported, but also interacts with the hydrophobic C-terminus and middle domain of pEAβ 3-42 to maintain an unordered conformation, effectively impeding the formation of initial oligomers and subsequently halting the aggregation of pEAβ 3-42 . Furthermore, TA can disrupt the "catalytic effect" of pEAβ 3-42 on amyloid aggregates, effectively suppressing Aβ aggregation and ultimately preventing the pathological events induced by Aβs., (© 2024 Wiley Periodicals LLC.)

Objective: To investigate the effect of Ganoderma Lucidum Spore Oil (GLSO) on the tumor growth and survival of H22 tumor-bearing mice treated with cyclophosphamide (CTX), and explore the underlying mechanism., Methods: Allograft H22 hepatocellular carcinoma mouse model was applied to investigate the effect of GLSO on the tumor growth and survival of animals, and Kaplan-Meier survival analysis was used to analyze the life span. Plasma biochemical examination was used to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (UREA) and creatinine (CRE). Western blot analysis was performed to detect Programmed Death-1 (PD-1), Programmed Death Ligand 1 (PD-L1), Janus Kinase 2 (JAK2), phosphorylated Signal Transducer and Activator of Transcription 3 (p-STAT3), and Signal Transducer and Activator of Transcription 3 (STAT3) expression., Results: GLSO increased the anti-tumor effect of CTX and prolonged the survival of H22 tumor-bearing mice treated with CTX. Meanwhile, GLSO increased the thymus index and showed no obvious toxicity to liver functions of animals. GLSO also decreased the level of UREA in H22 tumor-bearing mice treated with CTX. Furthermore, GLSO could inhibit the expression of PD-1 in spleen, which was independent of JAK2 expression and STAT3 phosphorylation. However, GLSO did not affect the expression of PD-L1, JAK2, and p-STAT3 in tumor tissue., Conclusion: GLSO could strengthen the anti-tumor effect of CTX and prolong the life span of H22 tumor-bearing mice, while the underlying mechanism might be relevant to the amelioration effect of thymus function and inhibition of PD-1 expression in spleen. Furthermore, these findings implied the promising role of GLSO in combination with CTX to extend the survival of patients in clinical chemotherapy of hepatocellular carcinoma.