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Purpose: HER2 expression is crucial for the application of HER2-targeted antibody-drug conjugates. This study aims to construct a predictive model by integrating multiparametric magnetic resonance imaging (mpMRI) based multimodal radiomics and the Vesical Imaging-Reporting and Data System (VI-RADS) score for noninvasive identification of HER2 status in bladder urothelial carcinoma (BUC)., Methods: A total of 197 patients were retrospectively enrolled and randomly divided into a training cohort (n = 145) and a testing cohort (n = 52). The multimodal radiomics features were derived from mpMRI, which were also utilized for VI-RADS score evaluation. LASSO algorithm and six machine learning methods were applied for radiomics feature screening and model construction. The optimal radiomics model was selected to integrate with VI-RADS score to predict HER2 status, which was determined by immunohistochemistry. The performance of predictive model was evaluated by receiver operating characteristic curve with area under the curve (AUC)., Results: Among the enrolled patients, 110 (55.8%) patients were demonstrated with HER2-positive and 87 (44.2%) patients were HER2-negative. Eight features were selected to establish radiomics signature. The optimal radiomics signature achieved the AUC values of 0.841 (95% CI 0.779-0.904) in the training cohort and 0.794 (95%CI 0.650-0.938) in the testing cohort, respectively. The KNN model was selected to evaluate the significance of radiomics signature and VI-RADS score, which were integrated as a predictive nomogram. The AUC values for the nomogram in the training and testing cohorts were 0.889 (95%CI 0.840-0.938) and 0.826 (95%CI 0.702-0.950), respectively., Conclusion: Our study indicated the predictive model based on the integration of mpMRI-based radiomics and VI-RADS score could accurately predict HER2 status in BUC. The model might aid clinicians in tailoring individualized therapeutic strategies., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To investigate corticospinal tract (CST) injury and remodeling in patients with basal ganglia intracerebral hemorrhage (ICH) and explore the characterization capabilities of the corresponding parameters. In this prospective study, baseline, scale, and diffusion-weighted imaging (DWI) data were collected from patient cohorts. Participants were stratified into favorable (0-3 points) and unfavorable (4-6 points) prognosis groups, based on Modified Rankin Scale (mRS) after 3-6 months. The analysis of DWI data was conducted employing FSL and DSI Studio software to compare CST injury between the prognosis groups and CST remodeling features. A partial correlation model was deployed to elucidate the characterization capability of CST-related parameters. Additionally, logistic regression analysis was applied to identify factors significantly influencing prognosis. A total of 65 patients were enrolled with a mean age of 53.52 years and a median hematoma volume of 23.60 ml. The 44 patients were classified within the favorable prognosis group, demonstrating a statistically significant difference in their lower mean age (P = 0.002). Additionally, 10 patients underwent DWI review with a mean age of 50.30 years and a median hematoma volume of 18.56 ml. The investigation uncovered evidence of CST damage versus remodeling at the group level, respectively, with statistical significance (FDR-corrected P < 0.05, 10,000 permutations). The fractional anisotropy (FA) ratio in the internal capsule region exhibited moderate correlation with motor function (r = 0.507, P < 0.001) and the 3- to 6-month mRS scores (r =  - 0.318, P < 0.013). Furthermore, binary logistic regression analysis identified the FA rate in the internal capsule as a significant influencing factor of prognosis (odds ratio = 1.027, 95% confidence interval = 1.003-1.052, P = 0.025). Basal ganglia ICH can coincide with injury to the CST, which could undergo repair over time. Additionally, the FA ratio of the internal capsule is a potential biomarker to characterize residual motor function and provide prognostic information., Competing Interests: Declarations. Ethics Approval and Consent to Participate: This study was approved by the Huashan Hospital Ethics Committee Affiliated with Fudan University (20201011 and 2022904). Informed consents were obtained from patients or their families before inclusion, and the study was conducted in conformity with the 1964 Declaration of Helsinki. Competing Interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Local relapse has not been eradicated even in the era of total mesorectum excision. 1,2 Although various approaches have been attempted, R0 resection remains the only potentially curative treatment. 3,4 PATIENT AND METHODS: A 45-year-old woman with a history of laparoscopic abdominoperineal resection was diagnosed with pelvic recurrence 7 months ago. Then, she received chemoradiotherapy. Magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) showed pelvic recurrences at the surface of the right piriformis and obturator internus, posterior vaginal wall, and presacral fascia. The patient also had bilateral hydronephrosis. No distant metastasis was found. First, the lateral pelvic lymph nodes were removed. Then, the internal iliac arteries and veins were transected. Next, the fibrotic ureters were isolated and cut. Then, presacral fascia at the S4 and S5 levels was excised. Anteriorly, the urethra and vagina were transected. Lastly, the suspected pelvic recurrent lesions were resected en bloc with partial right piriformis, obturator internus, and gluteus maximus through a combined abdominal and perineal approach. Greater omental pedicle flap was transplanted into the pelvic cavity and pelvic floor was reconstructed., Results: The operative time was 600 min, and blood loss was 400 ml. Postoperative course was uneventful, and the patient was discharged 14 days after surgery. Pathology report showed a moderately differentiated rectal adenocarcinoma invading the vagina, presacral fascia, and pelvic musculature. All margins were negative., Conclusions: As demonstrated by this case, image-guided total pelvic exenteration with presacral fascia and sidewall musculature excision provides an opportunity to cure pelvic recurrence of rectal cancer. 5 ., Competing Interests: Disclosure: The authors declare no conflicts of interest. Ethical Approval: This study was approved by the Ethics Committee of Changzheng Hospital., (© 2025. Society of Surgical Oncology.)

Objectives: Elderly frailty patients are at particular risk of sedation-related adverse events (SRAEs) during sedation. This study aimed to assess whether intravenous lidocaine could reduce the incidence of SRAEs in elderly frailty patients undergoing endoscopic retrograde cholangiopancreatography (ERCP)., Methods: A total of 210 elderly frailty patients scheduled for ERCP were randomly divided into two groups: lidocaine and control. Patients in the lidocaine group received intravenous lidocaine (1.0 mg/kg) before anesthesia induction, followed by continuous intravenous infusion (2.0 mg/kg/h) during ERCP. The control group received an equal volume of saline solution. The primary endpoint was the composite incidence of SRAEs during ERCP. Secondary endpoints were propofol consumption, VAS score, endoscopists' and patients' satisfaction scores and lidocaine-related adverse events and so on., Results: The composite incidence of SRAEs in the lidocaine group was significantly lower than in the control group (41.05% vs. 21.86%, p < 0.05). The propofol requirement (436.11 ± 118.90, 388.54 ± 149.65. p < 0.001) and VAS score of patients (3.02 ± 1.07, 2.54 ± 1.10. p < 0.05) in the lidocaine group were significantly lower than those in the control group. The endoscopists' satisfaction scores (7.77 ± 1.12, 8.23 ± 1.10. p < 0.05) and patients' satisfaction scores (8.53 ± 0.95, 8.98 ± 0.86. p < 0.05) in lidocaine group were significantly higher than those in the control group., Conclusions: Intravenous lidocaine can significantly decrease the incidence of SRAEs for ERCP procedures in elderly frailty patients, with no increase in lidocaine or other related adverse events., Trial Registration: Chinese Clinical Trial Registry (Trial ID: ChiCTR2300067796, https://www.chictr.org.cn/showproj.html?proj=185763 )., Competing Interests: Declarations. Disclosures: Hao Gao, Zhi-yu Yin, Li-xiao Hao, Jian Wang, Hao-liang Cai, Guo Jun, Xiao-fan Huang, Yue Yong, Yong-qiang Wang, Wen-ting Chen and Jian-gang Song have no conflicts of interest or financial ties to disclose., (© 2025. The Author(s).)

Key Message: A major locus Qfcr.cau-1B conferring resistance to Fusarium crown rot was identified and validated. The putative gene underlying this locus was pinpointed via virus-induced gene silencing. Fusarium crown rot (FCR), caused by various Fusarium pathogens such as Fusarium pseudograminearum and F. culmorum, is a severe soil-borne disease which significantly affected wheat (Triticum aestivum) production in many arid and semi-arid cropping regions of the world. In this study, a total of 5 QTLs associated with FCR resistance were detected on chromosomes 1B, 2B, 3A, 5A, and 7D using a population of 120 F 8 recombinant inbred lines (RIL) derived from a cross between two Chinese germplasm 20828 and SY95-71. A major locus Qfcr.cau-1B, which accounted for up to 28.33% of the phenotypic variation with a LOD value of 10.99, was consistently detected across all three trials conducted. The effect of Qfcr.cau-1B on FCR resistance was further validated using a F 5 RIL population between 20828 and BLS2. Integrated transcriptome and sequence variation analysis showed that three genes including TraesCS1B02G017700, TraesCS1B02G016400, and TraesCS1B02G022300 were potential candidate genes for Qfcr.cau-1B. Of these three genes, the virus-induced silencing of TraesCS1B02G022300 significantly promoted FCR severity, indicating its positive role in FCR resistance. Taken together, results from this study expand our understanding on genetic basis of FCR resistance in wheat and will be indicative for cloning genes conferring FCR resistance., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval: The experiments were performed in compliance with the current laws of China., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neuropathic pain is a type of pain caused by an injury or disease of the somatosensory nervous system. Currently, there is still absence of effective therapeutic drugs for neuropathic pain, so developing new therapeutic drugs is urgently needed. In the present study, we observed the effect of Comp 6d, a novel silent information regulator 1 (SIRT1) activator synthesized in our laboratory, on neuropathic pain and investigated the mechanisms involved. We found that both intrathecal and intraperitoneal injections of Comp 6d effectively alleviated neuropathic pain induced by chronic constriction injury (CCI) or spared nerve injury (SNI). However, the effect of Comp 6d on neuropathic pain was abolished in SIRT1 knockout mice. These results demonstrated that Comp 6d alleviated neuropathic pain by specifically activating SIRT1 in the spinal cord. Moreover, long-term intraperitoneal injection of Comp 6d had no significant side effects on heart, liver and kidney in SNI mice. Further study showed that the improvement of neuropathic pain by Comp 6d was mediated by the downregulation of mGluR1/5 levels and the subsequent inhibition of spinal neuronal activation. Taken together, the present findings suggest that the novel SIRT1 activator Comp 6d inhibits the activation of spinal cord neurons via the SIRT1-mGluR1/5 pathway, thereby attenuating neuropathic pain. Comp 6d is expected to be an effective therapeutic agent for neuropathic pain., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Augmented reality (AR) has emerged as a transformative technology in medical education, particularly in training basic laparoscopic skills. Despite its growing applications, the effectiveness of AR in this specific domain remains underexplored, with a lack of standardized assessment frameworks and inconsistent methodologies across studies. This systematic review and meta-analysis aimed to evaluate the effectiveness of AR in laparoscopic basic skills training for medical students and junior physicians., Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. Databases searched included PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. Studies were selected based on their focus on AR applications in laparoscopic training, involving both randomized controlled trials and non-randomized studies. Inclusion criteria focused on medical students and novice surgeons, assessing educational outcomes such as Global Operative Assessment of Laparoscopic Skills (GOALS) Global, Objective Structured Assessment of Technical Skills (OSATS) Global, OSATS Specific, Training Time, and Subjective Workload., Results: A total of 12 studies involving 434 participants met the inclusion criteria. The analysis revealed that AR technology significantly improved educational outcomes, with participants achieving higher GOALS and OSATS scores. Specifically, the mean difference for GOALS scores was 2.40 points (95% CI [1.30, 3.50], p < 0.001) and for OSATS scores, 7.71 points (95% CI [3.39, 12.03], p < 0.001). Additionally, AR-assisted training showed a reduction in subjective workload, with a mean decrease of 2.95 points (95% CI [- 4.95, - 0.95], p = 0.003)., Conclusions: The findings indicate that AR significantly enhances laparoscopic training outcomes, facilitating improved technical skills, efficiency, and learner independence. However, variability in study designs and outcomes limits generalizability. Future research should focus on standardize AR training protocols and evaluate long-term effectiveness to fully leverage AR's potential in surgical education., Competing Interests: Declarations. Disclosures: JianXiong, Xiaoqin Dai, Yuyang Zhang, Xingchao Liu and Xiyuan Zhou have no conflicts of interest or financial ties to disclose., (© 2024. The Author(s).)

Gliomas are the most prevalent type of primary brain tumor, with poor prognosis reported in patients with high-grade glioma. Kinesin family member 4 A (KIF4A) stimulates the proliferation, migration, and invasion of tumor cells. However, its function in gliomas has not been clearly established. Therefore, this study aimed to investigate the effects of KIF4A on the epithelial-mesenchymal transition and invasion of glioma cells. We searched The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases to identify KIF4A-related signaling pathways and downstream genes. We further validated them using western blotting, transwell migration and invasion, wound-healing scratch, and dual-luciferase reporter assays in U251 and U87 human glioblastoma cells. Our analysis of the Cancer Genome Atlas and Chinese Glioma Genome Atlas data showed elevated KIF4A expression in patients with gliomas and was associated with clinical grade. Here, KIF4A overexpression promoted the migration, invasion, and proliferation of glioma cells, whereas KIF4A knockdown showed contrasting results. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) analyses demonstrated that KIF4A positively controls TGF-β/SMAD signaling in glioma cells. Additionally, genetic correlation analysis revealed that KIF4A transcriptionally controls benzimidazoles-1 expression in glioma cells. KIF4A promotes the epithelial-mesenchymal transition by regulating the TGF-β/SMAD signaling pathway via benzimidazoles-1 in glioma cells., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: Not applicable, as neither human nor animal experimentation was performed in this study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study compared the effects of calcium oxalate stones and uric acid stones on male sexual function., Methods: We enrolled 100 patients with ureteral stones. According to the composition of the stones, they were divided into the calcium oxalate stone group and the uric acid stone group. All patients underwent ureteroscopic holmium laser lithotripsy. General data such as age, body mass index, course of disease, stone diameter, and degree of renal hydronephrosis were compared. Sperm parameters, including sperm density, sperm viability, and sperm deformity rate, as well as International Index of Erectile Function-5 questionnaire (IIEF-5) scores, and Quality of Life (QOL) scores, were measured and compared before and 6 weeks after the surgery., Results: There were no statistically significant differences in general data and sperm parameters between the two groups before the surgery (P > 0.05). However, there were significantly lower IIEF scores but significantly higher QOL scores in the uric acid stone group. In the calcium oxalate stone group, there were no statistically significant differences in sperm parameters, IIEF score, and QOL score before and after the surgery (P > 0.05). In the uric acid stone group, there were no statistically significant differences in sperm parameters before and after surgery (P > 0.05), whereas there were significantly higher IIEF scores but significantly lower QOL scores after the surgery (P < 0.05). The prevalence of erectile dysfunction (ED) in the uric acid stone group was 38.18% (21/55), which was significantly higher compared to 20.00% (9/45) in the calcium oxalate stone group (P < 0.05). The multivariate binary logistic regression analysis showed that the independent risk factor related to ED was uric acid stones (odds ratio: 2.637, 95% confidence interval 1.040-6.689, P = 0.041). No statistically significant differences were found in sperm parameters between patients with and without ED., Conclusion: Compared with the calcium oxalate stone group, patients with uric acid stones had a higher prevalence of ED and poorer sexual performance., Competing Interests: Declarations. Conflict of interest: All authors declare no conflicts of interest. Ethical approval: This study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and approved by the Ethics Committee of Suzhou Science and Technology Town Hospital. Informed consent: All patients have signed informed consent., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Osteosarcoma (OS) is a malignant bone sarcoma arising from mesenchymal stem cells. The biological role of Acyl-CoA synthetase long-chain family member 4 (ACSL4), recently identified as an oncogene in numerous tumor types, remains largely unclear in OS. In this study, we investigated the expression of ACSL4 in OS tissues using immunohistochemistry staining (IHC) staining of a human tissue microarray and in OS cells by qPCR assay. Our findings revealed a significant up-regulation of ACSL4 in both OS tissues and cells. To further understand its biological effects, we conducted a series of loss-of-function experiments using ACSL4-depleted MNNG/HOS and U-2OS cell lines, focusing on OS cell proliferation, migration, and apoptosis in vitro. Our results demonstrated that ACSL4 knockdown remarkably suppressed OS cell proliferation, arrested cells in the G2 phase, induced cell apoptosis, and inhibited cell migration. Additionally, a subcutaneous xenograft mice model was established to validate the in vivo impact of ACSL4, revealing ACSL4 silencing impaired tumor growth in the OS xenograft mice. Additionally, we discovered that ACSL4 could regulate the phosphorylation level of Smad2 through cooperative interactions, and treatment with a TGF-β inhibitor weakened the promoting effects of ACSL4 overexpression. In short, ACSL4 regulated OS progression by modulating TGF-β/Smad2 signaling pathway. These findings underscore ACSL4 as a promising therapeutic target for OS patients and contribute novel insights into the pathogenesis of OS., Competing Interests: Declarations. Conflict of interests: The authors declare that they have no conflicts of interest. Ethical approval: All experiments were approved by Ethical Committee of The Second Affiliated Hospital of Guangxi Medical University. Consent to participate: Informed consent was taken from all the participants. Consent to publish: The authors affirm that human research participants provided informed consent for publication of the images in Fig. 1., (© 2024. The Author(s).)

Bufalin, which is isolated from toad venom, exerts positive effects on hearts under pathological circumstance. We aimed to investigate the effects and mechanisms of bufalin on myocardial I/R injury. In vivo, bufalin ameliorated myocardial I/R injury, which characteristics with better ejection function, decreased infarct size and less apoptosis. The levels of pyroptotic proteins were increased in I/R-treated macrophages and inflammatory cytokines expressed more in I/R-induced mouse, which could be attenuated by bufalin. Bufalin also reduced H/R-treated macrophage pyroptosis in vitro. Autophagic flux blockage and ROS accumulation were reduced by bufalin in impaired macrophages. Overexpression of p62 abrogated the anti-proptosis and anti-oxidative effects of bufalin. The levels of apoptosis related proteins were changed and TUNEL-positive ratio was raised in cardiomyocytes that received conditioned medium treatment with H/R-treated macrophages, while bufalin pretreatment could reduce apoptosis. These findings indicate that bufalin may attenuate myocardial I/R injury by suppressing macrophage pyroptosis via P62 pathway., Competing Interests: Declarations. Ethics Approval: No human studies were carried out by the authors for this article. All the experiments complied with the guiding principles for the care and use of laboratory animals of Zhongshan Hospital, Fudan University and were approved by the Committee for Animal Experimentation. Disclosures: None. Conflict of Interest: All authors disclosed no relevant relationships., (© 2024. The Author(s).)

Purpose: Recurrent miscarriage (RM) is a distressing and complicated adverse pregnancy outcome. It is commonly recognized that insufficient decidualization could result in RM, but the molecular mechanisms of decidual impairment are still not fully understood. Thus, this study aimed to identify novel key genes potentially involved in RM and explore their roles played in endometrial decidualization., Methods: Initially, a combinative analysis of decidual and mid-secretory endometrial transcriptomes was performed to discover hub genes involved in the etiology of RM. And the expression levels of hub genes were evaluated in both primary decidual stromal cells (DSCs) and decidual tissues. Subsequently, the immortalized human endometrial cell line, T-HESCs, was used to investigate whether FXYD1 overexpression affects decidualization by regulating Na/K-ATPase activity., Results: FXYD domain containing ion transport regulator 1 (FXYD1) was identified as a hub gene in the pathogenesis of RM through various bioinformatic methods. Abnormally increased FXYD1 expression was observed in DSCs and decidual tissues from RM patients compared to that of the normal group. Furthermore, in vitro decidualization was obviously inhibited by the overexpression of FXYD1. Additionally, Na/K-ATPase activity was significantly elevated during decidualization, whereas overexpression of FXYD1 reduced Na/K-ATPase activity. Bufalin, a Na/K-ATPase inhibitor, showed an effectively inhibitory effect on decidualization., Conclusions: Collectively, FXYD1 was discovered as a hub gene associated with RM, and its expression levels in RM patients were significantly upregulated. Increased FXYD1 expression might lead to decidualization defects by reducing Na/K-ATPase activity, of which presented a novel prospective treatment target for RM., Competing Interests: Declarations. Ethics approval: This study involving human was approved by the Medical Ethics Committees of The Second Hospital of Tianjin Medical University (KY2017K002) and the Shanghai Institute for Biomedical and Pharmaceutical Technologies (PJ2018-06). Informed consent: Written informed consent was obtained from all participants. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ferroptosis is a novel type of programmed cell death dependent on iron and is characterized by the accumulation of lipid peroxides, which is involved in acute lung injury (ALI). Brazilin, an organic compound known for its potent antioxidant and anti-inflammatory properties, has not been thoroughly studied for its potential impact on lipopolysaccharide (LPS)-induced ALI. Here, we found that pretreatment of brazilin mitigated LPS-induced lung injury and inflammation by inhibiting mitochondrial oxidative stress and ferroptosis, both in vivo and in vitro. Sirtuin 3 (SIRT3) was identified as a downstream target of brazilin, and overexpression of SIRT3 mirrored the protective effects of brazilin against LPS-induced ALI. Additionally, SIRT3 contributed to the upregulation, mitochondrial translocation and deacetylation of glutathione peroxidase 4 (GPX4). Through screening potential acetylation sites on GPX4, we identified lysine 148 (K148) as the residue deacetylated by SIRT3. Mutating the acetylation site of GPX4 within mitochondria (mitoGPX4-K148R) reduced LPS or SIRT3 knockdown-induced GPX4 acetylation, oxidative stress, and ferroptosis, ultimately ameliorating ALI. In conclusion, our study demonstrates the beneficial effects of brazilin in treating LPS-induced ALI. Brazilin enhances SIRT3 expression, which in turn deacetylates and facilitates the mitochondrial translocation of GPX4, thereby reducing mitochondrial oxidative stress and ferroptosis. These findings suggest that the SIRT3/GPX4 pathway may represent a critical mechanism, and brazilin emerges as a promising therapeutic candidate for ALI., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pancreatic neuroendocrine neoplasms (pNENs) are the second most common pancreatic malignancy. While most cases are sporadic, a small proportion is associated with genetic syndromes, such as Multiple Endocrine Neoplasia (MEN), Von Hippel-Lindau Syndrome (VHL), Neurofibromatosis Type 1 (NF1), and Tuberous Sclerosis Complex (TSC). This review aims to use pNENs as a clue to reveal the full spectrum of disease, providing a comprehensive understanding of diagnosis. It aids in promptly identifying abnormalities in other organs, recognizing familial genetic mutations, and achieving personalized treatment., Competing Interests: Declarations. Institutional review board statement: Not applicable. Informed consent: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To elucidate the mechanism by which tyrosine phosphatase SHP2 protects CRC through modulation of TFEB-mediated ferritinophagy, thereby suppressing ROS and ferroptosis., Methods: SW480 and SW620 cells, in the logarithmic growth phase, were treated with or without the SHP2 inhibitor PHPS1, the activator Trichomide A, EGF, or MMP inhibitors, and randomly assigned to four groups. Additionally, SW480 cells in the logarithmic phase underwent treatments with EGF, the ferroptosis inducer erastin, Trichomide A, or the curcumin analog C1, forming seven groups. Cell migration assessment in these groups employed scratch and Transwell assays. Protein expression analysis of total SHP2, total PI3K, p-SHP2, p-PI3K, p-TFEB, TFEB, SQSTM1, LC3, LAMP2, NCOA4, FTH1, GPX4, NOX4, and ACSL4 in the seven SW480 groups was conducted through Western blot and immunofluorescence. Apoptosis analysis was performed on these seven groups, while gene co-expression analysis utilized bioinformatics. SW480 and CCD-841CoN cells were categorized into four groups, undergoing treatment with saline, EGFR-OE lentivirus, SHP2-KD lentivirus, or SHP2-OE lentivirus. Western blot analysis in SW480 cells detected EGFR, total SHP2, p-SHP2, GPX4, and ACSL4 proteins, and tumor volume observations were conducted in a nude mouse xenograft model. Western blot also evaluated total SHP2, p-SHP2, GPX4, and ACSL4 protein expression in CCD-841CoN cells., Results: Bioinformatics analysis revealed correlations between EGFR and SHP2, SHP2 and PIK3CA, SHP2 and MAPK1, BRK4 and HIF1A, HIF1A and NCOA4, as well as TFEB and FTH1. Scratch and Transwell assays showed that SHP2 diminishes the migratory capacity of SW480 and SW620 cells. Western blot and immunofluorescence demonstrated that EGFR activation of SHP2 markedly elevated p-TFEB levels while reducing TFEB protein expression. EGF stimulation enhanced the expression of FTH1, GPX4, NOX4, and ACSL4. Combined stimulation with EGF and SHP2 further amplified the expression of p-SHP2, p-TFEB, and NCOA4 while reducing TFEB, SQSTM1, LC3, and LAMP2. Erastin augmented FTH1, GPX4, NOX4, and ACSL4 expression while decreasing p-SHP2, p-TFEB, TFEB, SQSTM1, LC3, LAMP2, and NCOA4. TFEB activation suppressed p-SHP2, p-TFEB, NCOA4, FTH1, and GPX4 expression, while promoting TFEB, SQSTM1, LC3, LAMP2, NOX4, and ACSL4 expression. Apoptosis assays indicated that SHP2 activation decelerated apoptosis in SW480 cells, whereas erastin under EGF stimulation accelerated apoptosis, as did TFEB activation. Western blot results in SW480 cells displayed that overexpression of EGFR or SHP2 significantly increased total SHP2, p-SHP2, and GPX4 expression while decreasing ACSL4 levels. SHP2 knockdown decreased total SHP2, p-SHP2, and GPX4 expression, with an increase in ACSL4 expression. In CCD-841CoN cells, overexpression of EGFR or SHP2 resulted in a decrease in p-SHP2 and an increase in total SHP2, more pronounced with SHP2 overexpression, while GPX4 and ACSL4 levels remained stable. SHP2 knockdown led to reduced EGFR, total SHP2, p-SHP2, and GPX4 expression, without a significant impact on ACSL4 levels. The nude mouse xenograft model demonstrated that EGFR overexpression significantly increased tumor size, whereas SHP2 overexpression markedly decreased tumor volume. SHP2 knockdown resulted in significantly larger tumors., Conclusion: SHP2 advances CRC progression by modulating TFEB-mediated ferritinophagy, suppressing ROS and ferroptosis. Targeting SHP2 presents a promising therapeutic strategy for CRC., Competing Interests: Declarations. Ethics approval and consent to participate: This study has been People’s Liberation Army by the Medical Ethics Committee of the 980 Hospital of the Joint Logistics Support Unit. Medical Ethics Committee of the 98O Hospital of the Joint Logistics Support Force of the People's Liberation Army of China (2024-KY-87). Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To construct a predictive model using deep-learning radiomics and clinical risk factors for assessing the preoperative histopathological grade of bladder cancer according to computed tomography (CT) images., Methods: A retrospective analysis was conducted involving 201 bladder cancer patients with definite pathological grading results after surgical excision at the organization between January 2019 and June 2023. The cohort was classified into a test set of 81 cases and a training set of 120 cases. Hand-crafted radiomics (HCR) and features derived from deep-learning (DL) were obtained from computed tomography (CT) images. The research builds a prediction model using 12 machine-learning classifiers, which integrate HCR, DL features, and clinical data. Model performance was estimated utilizing decision-curve analysis (DCA), the area under the curve (AUC), and calibration curves., Results: Among the classifiers tested, the logistic regression model that combined DL and HCR characteristics demonstrated the finest performance. The AUC values were 0.912 (training set) and 0.777 (test set). The AUC values of clinical model achieved 0.850 (training set) and 0.804 (test set). The AUC values of the combined model were 0.933 (training set) and 0.824 (test set), outperforming both the clinical and HCR-only models., Conclusion: The CT-based combined model demonstrated considerable diagnostic capability in differentiating high-grade from low-grade bladder cancer, serving as a valuable noninvasive instrument for preoperative pathological evaluation., Competing Interests: Declarations. Ethical approval: Affiliated Hospital of Guizhou Medical University, We hereby approve the submission of the article entitled "A multimodal deep-learning model based on multichannel CT radiomics for predicting pathological grade of bladder cancer" by Ting Zhao, Qinghong Duan, et al at Department of Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China. As its content complies with the relevant regulatory requirements on medical ethics and does not infringe on patient privacy or involve any commercial interest. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Organoids are rapidly self-organizing 3D in vitro cultures derived from pluripotent stem cells (PSCs) or adult stem cells (ASCs) that possess disease-like characteristics with high success rates. Due to their ability to retain tissue structure, biological phenotypes, and genetic information, they have been utilized as a novel in vitro model for disease research. In recent years, scientists have established self-organizing 3D organoids for human endometrium, fallopian tubes, ovaries, and cervix by culturing stem cells with cytokines in 3D scaffolds. The integration of organoids with animal models, organ-on-a-chip systems, and 3D printing technologies offers a novel preclinical model for exploring disease mechanisms and developing treatments. This review elaborate on the recent research progress of stem cells-formed organoids in the field of gynecology from the aspects of constructing gynecological disease organoids, drug screening and new drug development, simulation modeling, allogeneic transplantation, regenerative medicine and personalized treatment.", Competing Interests: Declarations. Ethics Approval and Consent to Participate: Not applicable. Consent of Publication: Not applicable. Competing Interests: The authors declare that there is no competing interest., (© 2024. The Author(s).)

Competing Interests: Disclosure: The authors declare no competing financial or nonfinancial interests.

Brain arteriovenous malformations (bAVMs) are a major cause of hemorrhagic stroke in children and young adults. These lesions are thought to result from somatic KRAS/BRAF mutations in brain endothelial cells (bECs). In this study, we introduce a new bAVM model by inducing a brain endothelial-specific Braf V600E mutation using the Slc1o1c1(BAC)-CreER driver line. The pathological characteristics of this model resemble human bAVMs, including dilated and hyperpermeable vessels, as well as parenchymal hemorrhage. We observed that these lesions showed a typical reduction in pericyte coverage and disruption of the pericyte-endothelial cell connection. Additionally, we found that ANGPT2 levels were significantly increased in the endothelium of bAVM lesions, which may be a critical factor in the pericyte deficits of the malformed vessels. Treatment with an ANGPT2 neutralizing antibody confirmed that blocking ANGPT2 can restore pericyte density in bAVM lesions, improve pericyte coverage around microvessels, enhance tight junction protein coverage related to endothelial cells, and normalize endothelial barrier function. In summary, our findings suggest that increased ANGPT2 expression in endothelial cells with the Braf V600E mutation is a key factor in pericyte deficiencies in bAVMs, highlighting the potential effectiveness of anti-ANGPT2 therapy in treating bAVMs., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: To explore the diagnostic efficacy of advanced intelligent clear-IQ engine (AiCE) and adaptive iterative dose reduction 3D (AIDR 3D), combination with and without the black blood CT technique (BBCT), for detecting vascular invasion in patients diagnosed with nonmetastatic pancreatic ductal adenocarcinoma (PDAC)., Methods: A total of 35 consecutive patients diagnosed with PDAC, proceeding with contrast-enhanced abdominal CT scans, were enrolled in this study. The arterial and portal venous phase images were reconstructed using AiCE and AIDR 3D. The corresponding BBCT images were established as AiCE-BBCT and AIDR 3D-BBCT, respectively. Two observers scored the image quality independently. Cohen's kappa (k) value or intraclass correlation coefficient (ICC) was used to analyze consistency. The diagnostic performance of four algorithms in detecting vascular invasion in PDAC patients was assessed using the area under the curve (AUC)., Results: The AiCE and AiCE-BBCT groups demonstrated superior image noise and diagnostic acceptability compared with AIDR 3D and AIDR 3D-BBCT groups (all p < 0.001), and the k value was 0.861-0.967 for both reviewers. In terms of diagnostic capability for vascular invasion in PDAC, the AiCE-BBCT group exhibited higher specificity (95.0%) and sensitivity (93.3%) compared to the AIDR 3D and AIDR 3D-BBCT groups, with an AUC of 0.942 (95% CI: 0.849-1.000, p < 0.05). Furthermore, all vascular evaluations conducted using AiCE-BBCT demonstrated better consistency (ICC: 0.847-0.935)., Conclusion: The BBCT technique in conjunction with AiCE could lead to notable enhancements in both the image quality of PDAC images and the diagnostic performance for tumor vascular invasion., Critical Relevance Statement: Better diagnostic accuracy of vascular invasion of PDAC based on BBCT in combination with an AiCE is a critical factor in determining treatment strategies and patient outcomes., Key Points: Identifying vascular invasion of PDAC is important for prognostication. Combined images provide improved image quality and higher diagnostic accuracy. Combined images can excellently display the vascular wall and invasion., Competing Interests: Declarations. Ethics approval and consent to participate: The research received ethical approval from the Institutional Ethics Committee at China–Japan Friendship Hospital and was conducted following the principles outlined in the Declaration of Helsinki. Competing interests: Y.X. and J.W. are affiliated with Canon Medical Systems. The remaining authors declare that they have no competing interests. Consent for publication: Not applicable., (© 2024. The Author(s).)

Occupational and unintentional exposure of zinc oxide nanoparticles (ZnONPs) raises concerns regarding their neurotoxic potential and there is an urgent need for the development of effective agents to protect against the toxic effects of ZnONPs. Astragalus memeranaceus (AM), a famous Traditional Chinese Medicine, as well as its bioactive components, showing a potential neuroprotective function. This study aims to investigate the neuroprotective effects of bioactive components of AM against ZnONPs-induced toxicity in human neuroblastoma SH-SY5Y cells and its underlying mechanisms. The cell apoptosis, ROS generation, MMP changes, mitochondrial fission/fusion, biogenesis, and mitophagy were assessed. In this study, AM treatment inhibited ZnONPs-induced cell apoptosis and ROS overproduction in SH-SY5Y cells. And astragaloside IV (ASIV) played a dominant role in the attenuation of cytotoxicity after ZnONPs exposure, rather than flavonoids and polysaccharides. ASIV treatment significantly reduced ROS generation and MMP collapse in ZnONPs-exposed cells. Furthermore, the protein expressions of mitochondrial biogenesis (PGC-1α), fusion (Mfn1 and Mfn2), and fission (Drp1) were markedly increased. Meanwhile, the PINK1/Parkin-mediated mitophagy was activated after ASIV administration, which ameliorated ZnONPs-induced SH-SY5Y cell death. Collectively, ASIV administration mitigated ZnONPs-induced cytotoxicity in SH-SY5Y cells through restoring mitochondrial quality control process, which hinted the protective role of ASIV in ZnONPs-induced neurotoxicity., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest. Consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cell pyroptosis is a form of programmed cell death, with Gasdermin-D (GSDMD) acting as its key executor. While activating pyroptosis represents a promising therapeutic strategy for cancer, the regulatory mechanisms governing GSDMD expression during cell death remain poorly understood. In this study, we identified METTL3 as a negative regulator of GSDMD-mediated pyroptosis, with high expression in breast cancer (BC) cells. YTHDF2 was found to recognize the m6A modification of GSDMD, thereby decreasing its stability. Finally, in vivo experiments further demonstrated the inhibitory effect of the METTL3 inhibitor STM2457 on tumors. Overall, these findings suggest that inhibition of METTL3 can enhance GSDMD-mediated pyroptosis and reveal a novel regulatory mechanism governing GSDMD expression, presenting a novel strategy for cancer treatment., Competing Interests: Declarations. Competing interest: The authors declare no competing interests. Ethical approval: This study was approved by the Institutional Research Ethics Committee of the Cancer Hospital at the Chinese Academy of Medical Sciences, in accordance with the Declaration of Helsinki. All animal experiments were approved by the Animal Experiment Ethics Committee of the Chinese Academy of Medical Sciences Cancer Hospital., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The rapid development of communication technology and high-frequency electronic devices has created a need for more advanced electromagnetic interference (EMI) shielding materials. In response to this demand, a study has been conducted to develop multifunctional carbon nanofibers (CNFs)/polyaniline (PANI) aerogels with excellent electromagnetic interference shielding, flame retardancy, and thermal insulation performance. The process involved freeze-drying of electrospun CNFs and PANI nanoparticles followed by in situ growth PANI to coat the CNFs, creating the core-shell structured CNFs/PANI composite fiber and its hybrid aerogels (CP-3@PANI). The interaction between PANI and aniline (ANI) provides attachment sites, allowing additional ANI adsorption into the aerogel for in situ polymerization. This results in PANI uniformly covering the surface of the CNFs, creating a core-shell composite fiber with a flexible CNF core and PANI shell. This process enhances the utilization rate of the ANI monomer and increases the PANI content loaded onto the aerogel. Additionally, effective connections are established between the CNFs, forming a stable, conductive three-dimensional network structure. The prepared CP-3@PANI aerogels exhibit excellent EMI shielding efficiency (SE) of 85.4 dB and specific EMI SE (SE d -1 ) of 791.2 dB cm 3  g⁻ 1 in the X-band. Due to the synergistic flame-retardant effect of CNFs, PANI, and the dopant (phytic acid), the CP-3@PANI aerogels demonstrate outstanding flame-retardant and thermal insulation properties, with a peak heat release rate (PHRR) as low as 7.8 W g⁻ 1 and a total heat release of only 0.58 kJ g⁻ 1 . This study provides an effective strategy for preparing multifunctional integrated EMI shielding materials., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. They have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s).)

Introduction: Most oncogenic genes contribute to cancer progression, but their role and regulatory mechanisms are not yet fully understood in hepatocellular carcinoma (HCC). This study aimed to explore the role of miR-328-3p and the regulatory relationship between miR-328-3p and HMOX1 in HCC., Methods: We utilized Cox and LASSO regression to identify a panel of oncogenic genes associated with hepatocellular carcinoma (HCC) progression within the TCGA-LIHC cohort and the GSE104580 dataset. The expression levels of the hub gene, HMOX1, were assessed in HCC cell lines using qPCR. The functional roles of miR-328-3p and HMOX1 were evaluated through a series of in vitro assays, including CCK-8 for proliferation, colony formation, wound healing, and Transwell assays for migration and invasion. The direct interaction between miR-328-3p and HMOX1 was explored using a luciferase reporter assay, Western blot (WB) for protein expression analysis, and functional assays to determine the impact on cell proliferation and migration., Results: Eight candidate genes (BIRC5, TNSF4, SPP1, HMOX1, ADM, RBP2, IGF1, and LECT2) were screen out. The hub gene HMOX1 among had high expression level in HCC cell lines. High HMOX1 expressing cell line had significantly increased proliferation and migration capacities. Moreover, HMOX1 was identified as a target of miR-328-3p, which regulated the HMOX1 expression in qPCR and WB assays. High miR-328-3p expressing HCC cell had diminished capacities for proliferation and migration. However, concurrent upregulation of HMOX1 expression resulted in enhanced proliferative and migratory abilities in these cells., Conclusion: Our study has advanced our understanding of the roles of miR-328-3p and HMOX1 in HCC, demonstrating the inhibitory effect of miR-328-3p on the oncogenic activity of HMOX1. Hence, these results revealed the function of miR-328-3p and a novel mechanistic pathway for HCC and suggested the potential therapeutic targeting of miR-328-3p and HMOX1 for HCC intervention strategies., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The immune checkpoint inhibitor therapy represented by blocking programmed cell death protein 1/ programmed cell death-ligand 1 (PD-1/PD-L1) has made significant progress in melanoma treatment. However, the response rate and therapeutic effect of immunotherapy alone are still not ideal for melanoma. In this study, we aimed to evaluate the defects of treating anti-PD-L1 alone and the therapeutic effect and molecular mechanism of combined therapy with anti-PD-L1 and MnCl 2 . We detected the changes of immune cell populations after anti-PD-L1 treatment in melanoma xenograft mouse model. Further, we evaluated the regulatory effect of MnCl 2 on dendritic cells (DCs) maturation in vitro. Next, we tested the therapeutic effect and regulatory effect on the tumor microenvironment with anti-PD-L1 and MnCl 2 via combining treatment with anti-PD-L1 and MnCl 2 . Anti-PD-L1 therapy has a certain tumor suppressive function, but the effect is not ideal. The results of flow cytometry showed that the number of CD4 + T cells and CD8 + T cells significantly increased after anti-PD-L1 treatment. However, the number of DCs remained basically unchanged after anti-PD-L1 treatment. In vitro, we confirmed that MnCl 2 significantly promoted DCs maturation vis activating cGAS-STING signaling pathway. The combination of anti-PD-L1 and MnCl 2 displayed the best tumor suppression effect in melanoma xenograft mouse model. In tumor microenvironment, the infiltration of T cells and the maturation of DCs were significantly promoted, demonstrating a strong anti-tumor immune response. In summary, we conclude that combining anti-PD-L1 with MnCl 2 is a promising therapeutic strategy for melanoma., Competing Interests: Declarations. Ethics approval: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In Asia-Pacific region, hepatocellular carcinoma is a serious health threat attributing to over 600,000 deaths each year and account for over 70% of global cases. Clinically, the major unmet needs are recurrence after curative-intent surgery, liver transplantation or local ablation and disease progression in those with hepatocellular carcinoma not eligible for resection or failed locoregional therapy. In the recent few years, new targeted therapy and immune-checkpoint inhibitors have been registered as systemic therapy to address these issues. Notably, new forms of systemic therapy, either as first-line or second-line therapy for unresectable hepatocellular or those not eligible for locoregional therapy, are now available. New data is also emerging with the use of systemic therapy to prevent hepatocellular carcinoma recurrence after curative-intent resection or local ablation therapy and to retard disease progression after locoregional therapy. In the future, further implementation of immune-checkpoint inhibitors and other forms of immunotherapy are expected to bring a new paradigm to the management of hepatocellular carcinoma. New insight related to immune-related adverse events with the use of immunotherapy has allso enabled optimization of the therapeutic approach to patients with hepatocellular carcinoma. The purpose of this clinical practice guideline is to provide an up-to-date recommendation based on clinical evidence and experience from expert Asia-Pacific key opinion leaders in the field of hepatocellular carcinoma. Three key questions will be addressed, namely: (1) Which patients with hepatocellular carcinoma should be considered for systemic therapy? (2) Which systemic therapy should be used? (3) How should a patient planned for immune checkpoint-based systemic therapy be managed and monitored?, Competing Interests: Declarations. Conflict of interest: George LAU reported lecture fees from AstraZeneca. Shuntaro OBI reported research grants from Eisai, Otsuka pharmaceutical, and Mochida pharmaceutical. Ryosuke TATEISHI reported lecture fees from Abbvie, AstraZeneca, Chugai, Eisai, Gilead Sciences, MSD and Takeda. Sadahisa OGASAWARA reported honoraria from Bayer, Eisai, Eli Lilly, consulting or advisory fees from Bayer, Eisai, Merck & Co. Inc., Chugai Pharma, Eli Lilly, and research grants from Bayer and Eisai. Naoya KATO reported honoraria payment from Bayer and Chugai; research funding from Bayer, Chugai, and Roche. Stephen L CHAN reported consulting or advisory board fees from AstraZeneca, Eisai, and MSD; reports being an invited speaker for AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, IPSEN, MSD, and Roche; and research funding from Bayer, Eisai, IPSEN, MSD, and Sirtex Medical. Yoshiyuki UENO reported honoraria payment from Chugai and Eisai. Ann-Lii CHENG reported consulting or advisory board fees from AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Eisai, Genentech/Roche, Ipsen, IQVIA, MSD, Ono Pharmaceutical, and Roche; and honoraria from AstraZeneca, Bayer, Eisai, and Genentech/Roche. Yock Young DAN reported consulting or advisory board fees from Boehringer Ingelheim, MSD, Norvo Nordisk, Roche, and research grants from MSD, Norvo Nordisk, Perspectum, Siemens. Jeong Min LEE reported lecture fees from Samsung Medison, GE Healthcare, Philips Healthcare, Starmed, and research grants from Samsung Medison, Siemens Healthineers, Philips Healthcare, GE Healthcare, Bayer, Guerbet, CMS, Canon Healthcare, Dongkuk Pharma. Diana A. Payawal reported lecture, consulting or advisory board fees from Gilead Sciences, Mylan Pharmaceuticals, Echosense, Getz and Abbott. Ekaphop SIRACHAINAN reported honoraria payment from MSD, Sanofi/Aventis, Merck, Amgen, Roche, Mundipharma, AstraZeneca, LF Asia, Diethelm Keller Group, Bristol Myers Squibb, Boehringer Ingelheim, Taiho Pharmaceutical, Dr Reddy's Laboratories, Zuellig Pharma, Meda Pharmaceuticals, Pfizer, Novo Nordisk, Novartis. Tawesak Tanwandee reported research grants from Bristol Myers Squibb and Merck. Masao Omata reported lecture, consulting or advisory board fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Otsuka, Astellas, Gilead Sciences, Chugai, Mitsubishi Tanabe, Kyorin, Merck Sharp and Dohme, Dainippon Sumitomo, Vertex Pharmaceuticals, Takeda, Merck Serono, and Zeria. Jian ZHOU, Shukui QIN, Haitao ZHAO, Motoyuki OTSUKA, Jacob GEORGE, Pierce KH CHOW, Jianqiang CAI, Shuichiro SHIINA, Osamu YOKOSUKA, Kyoko OURA, Thomas YAU, Ming KUANG, Minshan CHEN, Gregory CHENG, Wan-Long CHUANG, Oidov BAATARKHUU, Feng BI, Rino A GANI, Atsushi TANAKA, Wasim JAFRI, Ji-Dong JIA, Jia-Horng KAO, Kiyoshi HASEGAWA, Patrick LAU, Jun LIANG, Zhenwen LIU, Yinying LU, Hongming PAN, Salimur RAHMAN, Jinsil SEONG, Feng SHEN, Gamal SHIHA, Tianqiang SONG, Hui-Chuan SUN, Tsutomu MASAKI, Lai WEI, Jin Mo YANG, Jose D SALLANO, Yanqiao ZHANG,, A Kadir DOKMECI, Shu-sen ZHENG, Jia FAN, Sheung-Tat FAN and Shiv Kumar Sarin reported that they have no conflict of interest. Ethical approval: Not applicable. Informed consent: Not applicable., (© 2024. Asian Pacific Association for the Study of the Liver.)

Background: The magnesium depletion score (MDS) is a scoring system developed to predict magnesium deficiency based on pathophysiological factors that affect renal reabsorption. The relationship between systemic magnesium status and arthritis is unclear. The purpose of this study was to determine the association between the MDS and rheumatoid arthritis (RA) as well as osteoarthritis (OA)., Methods: This study was conducted through a cross-sectional survey of 20,513 adults aged ≥ 20 years who participated in NHANES from 2007 to 2018. The four dimensions of the MDS included diuretics, proton pump inhibitors, glomerular filtration rate, and excessive alcohol consumption. Univariate and multivariable-weighted logistic regression were used to assess the associations between MDS and RA/OA, and a test for trend was performed to analyze the presence of a dose-response relationship. Subgroup analyses and interaction tests were performed according to confounders., Results: After adjustment for all covariates, we found a graded dose-response relationship between MDS and RA or OA. When MDS was considered as a continuous variable, each onefold increase in MDS was associated with a 1.21-fold increase in the odds of having RA (OR = 1.21, 1.10, 1.33) and a 1.12-fold increase in the odds of having OA (OR = 1.12, 1.04, 1.21). There was an interaction of sex in the effect of MDS on RA (P interaction  = 0.004) and age in the effect of MDS on OA (P interaction  = 0.006). In addition, these associations were further confirmed in sensitivity and subgroup analyses., Conclusions: Our study identified significant dose-response associations between MDS and both RA and OA. More biological mechanisms are needed in the future to validate and clarify the results of this study., Competing Interests: Compliance with ethical standards. Disclosures: None., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Purpose: This study was designed to evaluate the efficacy of different periurethral structural reconstruction approaches to improve postoperative continence post robot-assisted radical prostatectomy (RARP), which remains a critical concern., Methods: This study included patients with prostate cancer who received single, combined, and nonreconstruction following RARP from April 2017 to May 2021. Medical details were recorded, and patients were followed up via phone or the outpatient clinic. Continence, potency recovery, and quality of life were evaluated. Continence rate was assessed by daily urinary pads use and was compared between groups with the Kaplan-Meier method. Potency recovery was assessed by the questionnaire score. All variables were further analyzed via univariable and multivariable regression analysis., Results: Sixty patients were included in nonreconstruction group. Fifty-two and 156 patients were included in the single and combined group, respectively. Across early postoperative follow-up period, both single and combined reconstruction group showed higher continence rate (p < 0.05). The combined approach showed an advantage over the single one in improving continence rate (p < 0.05). Univariable and multivariable regression analysis point to the reconstruction approach as an independent factor that affects postoperative continence recovery post RARP., Conclusions: Periurethral reconstruction approaches were found to be beneficial in promoting early continence recovery after RARP, without compromising preserved neurovascular bundle. Combination of anterior and posterior reconstruction could be more beneficial on continence recovery and should be considered in clinical practice., (© 2024. Society of Surgical Oncology.)

Introduction: Spinal chondrosarcoma exhibits higher invasiveness and a worse prognosis compared to chondrosarcoma in the extremities. The prognosis and therapeutic plan vary greatly among different pathological subtypes of chondrosarcoma. This study aimed to analyze the differences in clinical characteristics, molecular features, therapeutic effects, and prognostic factors among the subtypes of chondrosarcoma in the spine., Methods: A retrospective review was conducted on 205 patients with spinal chondrosarcoma. The clinical features and immunohistochemical (IHC) markers were compared among the pathological subtypes of chondrosarcoma grade 1, grade 2, grade 3, mesenchymal chondrosarcoma (MCS), dedifferentiated chondrosarcoma (DCS), and clear cell chondrosarcoma (CCCS). Chondrosarcoma grade 1/2/3 are collectively referred to as conventional chondrosarcoma (CCS) for multivariate survival analysis. Univariate and multivariate analyses were performed to investigate independent prognostic factors for overall survival (OS) and recurrence-free survival (RFS) in patients with spinal chondrosarcoma. Furthermore, independent prognostic factors for OS and RFS were identified in CCS and MCS., Results: MCS patients were younger than the other subtypes. Patients with chondrosarcoma grade 1/2 had better OS than those with chondrosarcoma grade 3, MCS and DCS, while only chondrosarcoma grade 1 patients showed better RFS than chondrosarcoma grade 2/3, MCS and DCS patients. Ki-67 index was higher in chondrosarcoma grade 3, MCS and DCS than chondrosarcoma grade 1/2. The comparison of IHC markers further highlighted the overexpression of P53/MDM2 in MCS and DCS. Gross total resection, including en-bloc and piecemeal resection, significantly improved OS and RFS for CCS patients, while only en-bloc resection significantly improved the prognosis of MCS patients. Chemotherapy appeared to be important for the OS of MCS patients., Conclusion: P53/MDM2 pathway was upregulated in MCS and DCS compared to chondrosarcoma grade 1/2. Radical tumor resection is crucial for the treatment of spinal chondrosarcoma, while MCS patients require further comprehensive treatments perioperatively., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This research project was examined and approved by the medical ethics committee of Shanghai Changzheng Hospital (2018SL004), and written informed consent was obtained from all patients or their legal guardians. Consent for publication: Informed consent was obtained from all subjects involved in the study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate the relationship of dyslipidemia and menopausal symptoms in Chinese menopausal women., Material and Methods: A total of 989 eligible participants with menopausal syndrome were recruited from outpatient clinics in several cities in China. Menopausal symptoms were assessed using the Chinese Menopause Rating Scale (CMRS), the Self-rating Depression Scale (SDS), and the Self-rating Anxiety Scale (SAS). Serum lipid profile was measured using enzyme colorimetry. The relationship between lipid profile and menopausal symptoms was assessed using Student's t test/nonparametric Mann-Whitney U test, Spearman's correlation test, and binary logistic regression analysis., Results: Among the 989 patients, 527 had dyslipidemia while 462 did not. Patients with dyslipidemia had significantly higher Self-rating Anxiety Scale (SAS) scores than those without (p < 0.001), while there was no significant difference in Self-rating Depression Scale (SDS) scores. Patients without dyslipidemia had higher scores on the Chinese Menopause Rating Scale (CMRS) vascular dimension compared to those with dyslipidemia (p = 0.003). The correlation test revealed that variables associated with dyslipidemia included age (p = 0.031), CMRS hot flashes dimension score (P = 0.003), and SAS score (p < 0.001). Regression analysis demonstrated that BMI (OR: 1.08, 95% CI: 1.01-1.16, p = 0.027), SAS scores (OR = 1.10, 95% CI = 1.07-1.13), vasomotor dimension (OR = 0.89, 95% CI = 0.83-0.95), physical dimension (OR = 0.96, 95% CI = 0.93-1.00), and social dimension (OR = 0.84, 95% CI = 0.74-0.95) were independently associated with an increased risk of dyslipidemia., Conclusions: This study showed that anxiety was associated with an unfavorable lipid profile, and menopausal depression seemed to have no relationship with lipid profile, while vasomotor symptoms appeared to be a favorable factor for dyslipidemia in Chinese menopausal women., Competing Interests: Declarations. Ethics approval: This study was approved by the ethics committee of Guangdong Provincial hospital of Chinese Medicine (B2013-074-01) on April 26, 2013. All participants provided written informed consent before participating in the study. Consent to participate: In the original survey, verbal and written informed consent was obtained from all respondents who were able to accept or decline their participation in the study. Consent for publication: Manuscript has been approved by all authors for publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

This study thoroughly examines the challenges in managing bilateral embolization, emphasizing intraoperative judgment. It aims to underscore the necessity of accurate etiological judgments and the limitations of cross-circulation thrombectomy. A 59-year-old male with hypertension and atrial fibrillation developed sudden limb twitching, progressing to limb paralysis and speech impairment. Neurological assessments identified multiple symptoms, while a head CT scan excluded intracranial hemorrhage. A mechanical thrombectomy revealed occlusions in the right internal cerebral artery (ICA) and left middle cerebral artery (MCA). Thrombus migration from the ICA terminus was misinterpreted as an escape from the anterior communicating artery, leading to unsuccessful thrombus retrieval. This study highlights the infrequency of bilateral embolic infarctions and intraoperative misjudgments arising from thrombus migration during thrombectomy. It underscores the limitations of cross-circulation thrombectomy and emphasizes a comprehensive risk-benefit analysis. The insights provided deepen the comprehension of thrombus migration patterns and inform strategies for bilateral embolism, focusing on optimal revascularization techniques., Competing Interests: Declarations. Conflict of interest: None declared. Ethics approval: This report was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University. Informed consent: Informed consent was obtained from the patient., (© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.)

Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study aimed to assess the impact of a lung-protective ventilation strategy utilizing transpulmonary driving pressure titrated positive end-expiratory pressure (PEEP) on the prognosis [mechanical ventilation duration, hospital stay, 28-day mortality rate and incidence of ventilator-associated pneumonia (VAP), survival outcome] of patients with Acute Respiratory Distress Syndrome (ARDS)., Methods: A total of 105 ARDS patients were randomly assigned to either the control group (n = 51) or the study group (n = 53). The control group received PEEP titration based on tidal volume [A tidal volume of 6 mL/kg, flow rate of 30-60 L/min, frequency of 16-20 breaths/min, constant flow rate, inspiratory-to-expiratory ratio of 1:1 to 1:1.5, and a plateau pressure ≤ 30-35 cmH 2 O. PEEP was adjusted to maintain oxygen saturation (SaO 2 ) at or above 90%, taking into account blood pressure], while the study group received PEEP titration based on transpulmonary driving pressure (Esophageal pressure was measured as a surrogate for pleural pressure using an esophageal pressure measurement catheter connected to the ventilator. Tidal volume and PEEP were adjusted based on the observed end-inspiratory and end-expiratory transpulmonary pressures, aiming to maintain a transpulmonary driving pressure below 15 cmH 2 O during mechanical ventilation. Adjustments were made 2-4 times per day). Statistical analysis and comparison were conducted on lung function indicators [oxygenation index (OI), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2)] as well as other measures such as heart rate, mean arterial pressure, and central venous pressure in two groups of patients after 48 h of mechanical ventilation. The 28-day mortality rate, duration of mechanical ventilation, length of hospital stay, and ventilator-associated pneumonia (VAP) incidence were compared between the two groups. A 60-day follow-up was performed to record the survival status of the patients., Results: In the control group, the mean age was (55.55 ± 10.51) years, with 33 females and 18 males. The pre-ICU hospital stay was (32.56 ± 9.89) hours. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was (19.08 ± 4.67), and the mean Murray Acute Lung Injury score was (4.31 ± 0.94). In the study group, the mean age was (57.33 ± 12.21) years, with 29 females and 25 males. The pre-ICU hospital stay was (33.42 ± 10.75) hours. The mean APACHE II score was (20.23 ± 5.00), and the mean Murray Acute Lung Injury score was (4.45 ± 0.88). They presented a homogeneous profile (all P > 0.05). Following intervention, significant improvements were observed in PaO 2 and OI compared to pre-intervention values. The study group exhibited significantly higher PaO 2 and OI compared to the control group, with statistically significant differences (all P < 0.05). After intervention, the study group exhibited a significant increase in PaCO2 (43.69 ± 6.71 mmHg) compared to pre-intervention levels (34.19 ± 5.39 mmHg). The study group's PaCO2 was higher than the control group (42.15 ± 7.25 mmHg), but the difference was not statistically significant (P > 0.05). There were no significant differences in hemodynamic indicators between the two groups post-intervention (all P > 0.05). The study group demonstrated significantly shorter mechanical ventilation duration and hospital stay, while 28-day mortality rate and incidence of ventilator-associated pneumonia (VAP) showed no significant differences. Kaplan-Meier survival analysis revealed a significantly better survival outcome in the study group at the 60-day follow-up (HR = 0.565, 95% CI: 0.320-0.999)., Conclusion: Lung-protective mechanical ventilation using transpulmonary driving pressure titrated PEEP effectively improves lung function, reduces mechanical ventilation duration and hospital stay, and enhances survival outcomes in patients with ARDS. However, further study is needed to facilitate the wider adoption of this approach., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted with approval from the Ethics Committee of Shanghai Sixth People’s Hospital. This study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all participants or their guardians. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The vertebral artery's morphological characteristics are crucial in spontaneous vertebral artery dissection (sVAD). We aimed to investigate morphologic features related to ischemic stroke (IS) and develop a novel prediction model. Out of 126 patients, 93 were finally analyzed. We constructed 3D models and morphological analyses. Patients were randomly classified into training and validation cohorts (3:1 ratio). Variables selected by LASSO - including five morphological features and five clinical characteristics - were used to develop prediction model in the training cohort. The model exhibited a high area under the curve (AUC) of 0.944 (95%CI, 0.862-0.984), with internal validation confirming its consistency (AUC = 0.818, 95%CI, 0.597-0.948). Decision curve analysis (DCA) indicated clinical usefulness. Morphological features significantly contribute to risk stratification in sVAD patients. Our novel developed model, combining interdisciplinary parameters, is clinically useful for predicting IS risk. Further validation and in-depth research into the hemodynamics related to sVAD are necessary., Competing Interests: Declarations. Ethical Approval: The Ethical Review Committee of West China Hospital of Sichuan University (Approval No. 2020(69)) and individual consent for this retrospective analysis was waived. Informed Consent: Individual consent for this retrospective analysis was waived. Competing Interests: The authors have no conflicts of interest to declare that are relevant to the content of this article., (© 2024. The Author(s).)

Context: Battery interface research can effectively guide battery design and material selection to improve battery performance. However, current electrode material interface studies still have significant limitations. In this paper, by employing DFT-D method, the influences of doping elements (boron, nitrogen, phosphorus, sulfur, and silicon) on the properties of C 60 fullerene, such as structural stability, electronic properties, and the adsorption and migration of lithium ion, are comprehensively investigated. It is demonstrated that doping can bolster the fullerene molecule's structural integrity and enhance charge transfer comparing with C 60 , thereby augmenting the material's electrical conductivity. Among the five doping elements, B-doping exhibits the most favorable adsorption energies, indicating a strong lithium binding affinity. This observation is supported with energy barrier of lithium ion migration. B-doping leads to an elevated barrier (0.37 eV) comparing with pristine C 60 (0.19 eV), whereas Si-doping significantly reduced barrier (0.038 eV) indicates enhanced lithium-ion mobility. These findings solid the efficacy of doping as a strategy to enhance the performance of fullerene electrodes., Method: All DFT calculations were performed using the VASP software package. The chosen computational technique was a combination of the generalized approximate gradient function PBE with the dispersion correction (DFT-D3) developed by Grimme. The results of the calculations were analyzed with the help of VASPKIT., Competing Interests: Declarations. Ethical approval: No applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neddylation, as a post-translational modification, has garnered significant attention in various tumor types recently. Few studies have investigated the involvement of neddylation-related genes (NRGs) in cutaneous melanoma (CM). Our study aims to identify prognostic NRGs and investigate their potential roles in CM. The RNA-sequencing data and corresponding clinical data of CM patients were retrieved from The Cancer Genome Atlas (TCGA) database, while the expression profiles of 812 normal skin specimens were obtained from the Genotype-Tissue Expression (GTEx) database. The neddylation-related genes (NRGs) were extracted from the Molecular Signatures Database (MSigDB). We identified differentially expressed NRGs in CM and determined neddylation-related prognostic genes through univariate Cox regression analysis. We constructed a novel NRGs signature using LASSO-COX. The accuracy and utility of the NRGs signature were evaluated via a variety of statistical methods. Bioinformatics tools were employed to investigate the differential biological functions and signaling pathways among distinct risk groups. The expression levels of NRGs were analyzed through RT-qPCR experiments conducted in vitro. Finally, we identified an 8-NRGs signature in CM. Our prognostic model exhibited a high predictive capability for outcomes. The differences in the proportions of immune cells among subgroups were statistically significant. The in vitro experiments indicated significant differences in the expression of our NRGs. The 8-NRGs signature serves as a prognostic model for CM. Importantly, the novel biological prognostic model holds potential for personalized therapy in CM patients., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All of the authors have read and approved the content, and agreed to submit it for consideration for publication. We confirmed that this paper has not been published elsewhere in whole or in part. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Efficient and stable photocathodes with versatility are of significance in photoassisted lithium-ion batteries (PLIBs), while there is always a request on fast carrier transport in electrochemical active photocathodes. Present work proposes a general approach of creating bulk heterojunction to boost the carrier mobility of photocathodes by simply laser assisted embedding of plasmonic nanocrystals. When employed in PLIBs, it was found effective for synchronously enhanced photocharge separation and transport in light charging process. Additionally, experimental photon spectroscopy, finite difference time domain method simulation and theoretical analyses demonstrate that the improved carrier dynamics are driven by the plasmonic-induced hot electron injection from metal to TiO 2 , as well as the enhanced conductivity in TiO 2 matrix due to the formation of oxygen vacancies after Schottky contact. Benefiting from these merits, several benchmark values in performance of TiO 2 -based photocathode applied in PLIBs are set, including the capacity of 276 mAh g -1 at 0.2 A g -1 under illumination, photoconversion efficiency of 1.276% at 3 A g -1 , less capacity and Columbic efficiency loss even through 200 cycles. These results exemplify the potential of the bulk heterojunction strategy in developing highly efficient and stable photoassisted energy storage systems., Competing Interests: Declarations. Conflict of interest: The authors declare no interest conflict. They have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s).)

Background: There is a lack of bibliometric analysis in research regarding primary therapy for end-stage renal disease (ESRD). This study aims to analyze the literature on ESRD therapy published over the past decade to understand current conditions and study trends for future research., Methods: Data were collected from the Web of Science Core Collection (WOSCC) database. Tools like CiteSpace 6.2.R4, 6.1.R6, VOSviewer 1.6.18, and Bibliometrix R4.1.1 were used to reveal research trends and hotspots. In addition, KEGG/GO analysis examined the probable functionalities of genes implicated in ESRD therapy to guide future research., Results: The bibliometric analysis presented in this paper indicates that the number of publications has remained relatively stable since 2013. The level of international collaboration is notably high, with the United States serving as the dominant research hub in this field. The University of California system is the most prolific institution, and Transplantation Proceedings is the most frequently published journal in this area. Kalantar-Zadeh, Kamyar is recognized as the most published and cited author. Keywords such as "secondary hyperparathyroidism," "uremic toxins," "cyclosporine," "mycophenolate mofetil," and "biomarkers" have seen a surge in interest recently, reflecting emerging research trends. Furthermore, inflammation and stem cell research have been identified as promising new therapeutic avenues for ESRD., Conclusion: This study identifies major areas, frontiers, and trends in research on primary treatments for ESRD, providing significant implications for future research., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Consensus regarding the hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer (CRC) regimen remains elusive. In this study, patient-derived tumor organoids from CRC were utilized as a preclinical model for in vitro drug testing of HIPEC regimens commonly used in clinical practice. This approach was used to facilitate the clinical formulation of HIPEC., Method: Tumor tissues and corresponding clinical data were obtained from patients diagnosed with CRC at the Sixth Affiliated Hospital of Sun Yat-Sen University. Qualified samples were cultured and passaged. We aimed to assess the sensitivity of in vitro hyperthermic perfusion using five different regimens, i.e. mitomycin C, mitomycin C combined with cisplatin, mitomycin C combined with 5-fluorouracil, oxaliplatin, and oxaliplatin combined with 5-fluorouracil., Results: Tumor organoids obtained from 46 patients with CRC were cultured, and in vitro hyperthermic perfusion experiments were conducted on 42 organoids using five different regimens. The average inhibition rate of mitomycin C was 85.2% (95% confidence interval [CI] 80.4-89.9%), mitomycin C combined with cisplatin was 85.5% (95% CI 80.2-90.7%), mitomycin C combined with 5-fluorouracil was 65.6% (95% CI 59.6-71.6%), oxaliplatin was 37.9% (95% CI 31.5-44.3%), and oxaliplatin combined with 5-fluorouracil was 40.7% (95% CI 33.9-47.5%)., Conclusion: In vitro hyperthermic perfusion demonstrates that the inhibition rate of mitomycin C, both alone and in combination with cisplatin, surpasses that of the combination of mitomycin C with 5-fluorouracil and oxaliplatin. In clinical practice, the combination of mitomycin C and cisplatin can be regarded as the optimal choice for HIPEC in CRC., (© 2024. The Author(s).)

Ferroptosis represents a newly programmed cell death, and the process is usually accompanied with iron-dependent lipid peroxidation. Importantly, ferroptosis is implicated in a myriad of diseases. Recent literature suggests a potential position of ferroptosis in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD), the most widespread liver ailment worldwide. Intriguingly, several functional genes and metabolic pathways central to ferroptosis are regulated by nuclear factor erythroid-derived 2-like 2 (NRF2). In current work, we aim to identify protocatechuic acid (PCA), a primary metabolite of antioxidant polyphenols, as a potent NRF2 activator and ferroptosis inhibitor in the hepatic lipotoxicity and steatosis models. Herein, both NRF2 +/+ and NRF2 -/- cell lines and mice were used to analyze the importance of NRF2 in PCA function, and hepatic lipotoxicity and steatosis models were induced by palmitic acid and high-fat diet respectively. Our results indicated that ferroptosis was mitigated by PCA intervention in hepatic cells. Furthermore, PCA exhibited therapeutic efficacy against ferroptosis, as well as hepatic lipotoxicity and steatosis. The protective role of PCA was predominantly mediated through NRF2 activation, potentially elucidating a pivotal mechanism underlying PCA's therapeutic impact on MAFLD. Additionally, the augmented mitochondrial TCA cycle activity observed in hepatic lipotoxicity and steatosis models was ameliorated by PCA, in part via NRF2-dependent pathways, further bolstering PCA's anti-ferroptosis properties. Collectively, our findings underscore PCA's potential in alleviating hepatic ferroptosis, lipotoxicity and steatosis via inducing activation of NRF2 signaling pathway, offering a promising strategy for the therapy of MAFLD as well as related lipid metabolic disorders., Competing Interests: Declarations: Ethical approval All animal studies received approval from the Ethics Committee on Biomedical Science in School of Medicine, Xi’an Jiaotong University (Approval number: 2022–1371) on June 9th, 2022. All experimental procedures were conducted in strict compliance with the Declaration of Helsinki, which is the guiding principle for the Ethics Committee on Biomedical Science at the School of Medicine, Xi’an Jiaotong University acts on. Conflicts of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Lenvatinib is a potent first-line therapy for patients with hepatocellular carcinoma (HCC), but it also increased the number of neutrophils in HCC tumor microenvironment., Methods: CitH3, MPO-DNA, elastase and MPO activity were measured for assessing neutrophil extracellular traps (NETs) in vivo and in vitro. Cell cuproptosis was assessed by measurement of copper content, FDX1, and pyruvate. The functions of lenvatinib, DNase I, interleukin 33 (IL33) neutralizing antibody and GPX4 in tumor growth were explored in mice., Results: Lenvatinib induced NETs in the HCC tumor microenvironment via HCC cells, but not through the direct stimulation of neutrophils. In addition, NET clearance by DNase I improves the efficacy of lenvatinib therapy in HCC mouse models. Mechanistically, lenvatinib promoted the expression and secretion of IL33 by HCC cells that triggered NET formation. Moreover, IL33 knockdown in Hepa1-6 cells improved lenvatinib efficacy in Hepa1-6-bearing HCC model mice and reduced NET formation in the tumor microenvironment. Subsequently, lenvatinib increased IL33 production by increasing the NDUFA4L2 expression in HCC cells. Furthermore, we found that IL33 triggered NET formation in neutrophils by increasing the protein expression of PADI4 via the Akt/mTOR signaling pathway. Rapamycin inhibition of mTOR reduced PADI4 expression and NET formation. Consistently, PADI4 inhibition by the selective PAD4 inhibitor GSK484 hydrochloride (GSK484) improved lenvatinib response to HCC therapy. Importantly, NETs contribute to lenvatinib resistance by inhibiting cuproptosis, but not apoptosis, pyroptosis, or ferroptosis in HCC cells. Treatment with GSK484 reversed the inhibitory effects of NETs on cuproptosis and sensitized the HCC cells to lenvatinib., Conclusions: Our study revealed that lenvatinib-induced NETs inhibited the cuproptosis of HCC cells, suggesting that targeting the IL33/PADI4/NET axis represents a promising therapeutic strategy for ameliorating lenvatinib resistance in HCC., Competing Interests: Declarations. Ethical approval: This animal study was approved by the Animal Care and Use Committee of the First Affiliated Hospital of Zhengzhou University with procedure number 2023-KY-1343. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Regional cerebral oxygen saturation (rSO 2 ) may vary in healthy individuals with different characteristics. Therefore, this study aimed to explore rSO 2 in a healthy population of western Sichuan. This cross-sectional study enrolled healthy volunteers from the Health Management Center and Inpatient Department of Ya'an People's Hospital, Ya'an Vocational and Technical College, Ya'an Geriatric University, and Liziping Yi Township in Shimian County, Ya'an City, Sichuan Province. Brain rSO 2 was measured by near-infrared spectroscopy (NIRS) between January 2020 and December 2022. A total of 661 volunteers were enrolled, with a mean age of 28.3 ± 23.1 years old and 276 males. There was significantly higher rSO 2 of the left brain in females (63.46 ± 3.01 vs. 63.17 ± 2.90, P = 0.015), males (63.91 ± 3.54 vs. 63.42 ± 3.32, P = 0.002), Han (65.10 ± 3.67 vs. 64.38 ± 3.43, P < 0.001), and volunteers aged 14-59 years (P < 0.05) compared with the right brain. Volunteers with Han ethnicity had significantly higher rSO 2 than those with Yi ethnicity (64.65 ± 3.29 vs. 62.68 ± 3.66, P < 0.001). Volunteers with past illness had significantly lower rSO 2 than those without past illness (62.41 ± 3.06 vs. 62.68 ± 3.66, P = 0.021). Pearson correlation analysis showed a significantly negative correlation of rSO 2 with age, ethics, past illness, and body mass index (BMI) but a significantly positive correlation with head circumference and height (all P < 0.05). The rSO 2 values in the left brain are significantly higher than in the right brain. Sex, ethnicity, age, BMI, and past illness are closely related to rSO 2 values in the healthy population., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures were performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. This study was approved by the Ethics Committee of Ya’an People’s Hospital (202201), Ya’an, China, and participants provided signed written informed consent forms. All methods were carried out in accordance with relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)