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Delian Kong,1,* Junrong Li,1,* Yingying Lv,1,* Man Wang,2,* Shenghua Li,1 Baoxin Qian,3 Yusheng Yu2 1Department of Neurology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, Jiangsu, 211100, People’s Republic of China; 2Department of Radiology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, Jiangsu, 211100, People’s Republic of China; 3Huiying Medical Technology (Beijing); Huiying Medical Technology Co., Ltd, Beijing City, 100192, People’s Republic of China*These authors contributed equally to this workCorrespondence: Delian Kong; Yusheng Yu, Email xykdl@163.com; yayiba2063@163.comObjective: To develop a radiomics nomogram model based on time-of-flight magnetic resonance angiography (TOF-MRA) images for preoperative prediction of true microaneurysms.Methods: 118 patients with Intracranial Aneurysm Sac (40 positive and 78 negative) were enrolled and allocated to training and validation groups (8:2 ratio). Findings of clinical characteristics and MRA features were analyzed. A radiomics signature was built on the basis of reproducible features by using the least absolute shrinkage and selection operator (LASSO) regression algorithm in the training group. The radiomics nomogram model was constructed by combining clinical risk factors and radiomics signature. In order to compare the classification performance of clinical models, radiomics model and radiomics nomogram model, AUC was used to evaluate them. The performance of the radiomics nomogram model was evaluated by calibration curve and decision curve analysis.Results: Eleven features were selected to develop radiomics model with AUC of 0.875 (95% CI 0.78– 0.97), sensitivity of 0.84, and specificity of 0.68. The radiomics model achieved a better diagnostic performance than the clinic model (AUC = 0.75, 95% CI: 0.53– 0.97) and even radiologists. The radiomics nomogram model, which combines radiomics signature and clinical risk factors, is effective too (AUC = 0.913, 95% CI: 0.87– 0.96). Furthermore, the decision curve analysis demonstrated significantly better net benefit in the radiomics nomogram model.Conclusion: Radiomics features derived from TOF-MRA can reliably be used to build a radiomics nomogram model for effectively differentiating between pseudo microaneurysms and true microaneurysms, and it can provide an objective basis for the selection of clinical treatment plans.Keywords: machine learning, radiomics, microaneurysms, nomogram

Fudong Rao,1,&ast; Zongjie Wang,2,&ast; Xijuan Chen,3 Linwei Liu,4 Bin Qian,1 Yanhua Guo4 1Department of Anesthesiology, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 2Department of Anesthesiology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, Fujian, People’s Republic of China; 3Department of Nephrology, Hematology and Pediatrics, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 4Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin QianDepartment of Anesthesiology, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, No. 602, Middle of Bayiqi Road, Fuzhou, 350004, People’s Republic of ChinaTel +86-158800 5016Fax +86-591-86250061Email 1547945960@qq.comYanhua GuoDepartment of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, No. 134, Dongjie, Fuzhou, 350001, People’s Republic of ChinaTel +86-8050333902Fax +86-591-88217841Email guoyanhua19@126.comPurpose: Ultrasound-guided thoracic paravertebral block (TPVB) has become increasingly popular for postoperative analgesia after breast surgery. We designed this prospective, randomized, double-blind, placebo-controlled trial to test the hypothesis that TPVB is superior to placebo in improving the patient quality of recovery following modified radical mastectomy.Patients and Methods: Sixty-eight female patients undergoing elective unilateral modified radical mastectomy were enrolled. Patients were randomized to receive preoperative ultrasound-guided TPVB with 0.5% ropivacaine (TPVB group, n=34) or 0.9% saline (Control group, n=34). The primary outcome was quality of recovery, measured 24 h after surgery using the 40-item Quality of recovery questionnaire (QoR-40). Secondary outcomes were the area under the curve of the visual analog scale pain scores over 24 h, postoperative 24-h morphine consumption, time to first rescue analgesia, length of post-anesthesia care unit stay, postoperative nausea and vomiting, and patient satisfaction.Results: The global QoR-40 score 24 h postoperatively (median [interquartile range]) was 173 [170– 177] in the TPVB group and 161 [160– 164] in the control group (P< 0.001), respectively, with a median difference (95% confidence interval) of 11 (9– 14). Compared with the control group, preoperative TPVB decreased the area under the curve of the visual analog scale pain scores over 24 h, reduced postoperative 24-h morphine consumption, prolonged the time to first rescue analgesia, shortened the length of post-anesthesia care unit stay, lessened postoperative nausea and vomiting, and improved the patient satisfaction.Conclusion: A single preoperative injection of TPVB with ropivacaine enhances the quality of recovery and postoperative analgesia in patients following modified radical mastectomy.Keywords: ultrasonography, thoracic paravertebral block, quality of recovery, regional anesthesia, pain management, breast cancer surgery

Bin Qian,1 Wenting Zheng,2 Jiawei Shi,2 Zihan Chen,2 Yanhua Guo,2 Yusheng Yao2 1Department of Anesthesiology, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 2Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Yanhua Guo Tel +86-591-88217841Email guoyanhua19@126.comPurpose: To compare the efficacy of intranasal dexmedetomidine and dexmedetomidine-ketamine premedication in preschool children undergoing tonsillectomy.Patients and Methods: We enrolled 66 children with American Society of Anesthesiologists physical status I or II, aged 3– 7 years undergoing tonsillectomy. Patients were randomly allocated to receive intranasal premedication with either dexmedetomidine 2 μg kg− 1 (Group D) or dexmedetomidine 2 μg kg− 1 and ketamine 2 mg kg− 1 (Group DK). The primary outcome was the sedation level assessed by the Modified Observer’s Assessment of Alertness/Sedation Scale (MOAA/S) 30 min after intervention. The minimal clinically relevant difference in the MOAA/S score was 0.5. Secondary outcomes included sedation onset time, parental separation anxiety, acceptance of mask induction, emergence time, emergence delirium, postoperative pain intensity, length of stay in the post-anesthesia care unit (PACU), and adverse effects.Results: At 30 min after premedication, the MOAA/S score was lower in Group DK than in Group D patients (median: 1.0, interquartile range [IQR]: 1.0– 2.0 vs median: 3.0, IQR: 2.0– 3.0; P< 0.001), with a median difference of 1.0 (95% confidence interval [CI]: 1.0– 2.0, P< 0.001). Patients in Group DK showed considerably faster onset of sedation (15 min, 95% CI: 14.2– 15.8 min) than Group D (24 min, 95% CI: 23.2– 24.8 min), with a median difference of 8.0 min (95% CI: 7.0– 9.0 min, P< 0.001). Both parental separation and facemask acceptance scores were lower in Group DK than in Group D patients (P=0.012 and P=0.001, respectively). There was no significant difference in emergence time, incidence of emergence delirium, postoperative pain scores, and length of stay in the PACU between the two groups.Conclusion: Intranasal premedication with a combination of dexmedetomidine and ketamine produced better sedation for pediatric tonsillectomy than dexmedetomidine alone.Keywords: preoperative sedation, mask induction, pediatric anesthesia

Bin Qian,1,* Shiwei Fu,2,* Yusheng Yao,3,4 Daoyi Lin,3 Li Huang3 1Department of Anesthesiology, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China; 2Department of Pathology, Union Hospital of Fujian Medical University, Fuzhou, Fujian, China; 3Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China; 4Department of Anesthesiology, Fujian Provincial Hospital, Fuzhou, Fujian, China *These authors contributed equally to this work Purpose: Chronic postsurgical pain is a challenging problem after breast cancer surgery. This prospective, randomized, double-blinded, parallel-group, placebo-controlled trial was conducted to evaluate the influence of preoperative ultrasound-guided multilevel paravertebral blocks (PVBs) on chronic pain following mastectomy. Patients and methods: One hundred eighty-four women were randomized to receive ultrasound-guided multilevel (T1–T5) PVBs with 5 mL of ropivacaine 0.5% or normal saline per level. The primary end point was the incidence of chronic pain at 3 months following mastectomy assessed by the brief pain inventory (BPI), while the secondary end points were the acute postoperative pain, the number of patients requiring rescue analgesia, postoperative nausea and vomiting (PONV), side effects, and chronic pain at 6 months after surgery assessed by the BPI. Results: A total of 172 patients completed the study. Ultrasound-guided multilevel PVBs significantly decreased immediate postoperative pain for the first 12 hours (P

Chang Zheng,1,2 Xuelian Li,2 Biyun Qian,3 Nannan Feng,3 Sumeng Gao,3 Yuxia Zhao,4 Baosen Zhou1,2 1Department of Clinical Epidemiology and Center of Evidence-Based Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, People’s Republic of China; 2Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, People’s Republic of China; 3Department of Epidemiology, School of Public Health, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China; 4Department of Radiotherapy, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People’s Republic of China Background: The leading cause of death for cancer is lung cancer, of which the majority subtype is non-small cell lung cancer (NSCLC). Recent studies have shown long non-coding RNAs are transcribed and contribute to cancer. Previous study has shown that a few single nucleotide polymorphisms (SNPs) in myocardial infarction associated transcript (MIAT) were associated with some diseases or function as competing endogenous RNA (ceRNA) in some cancer. Patients and methods: We performed bioinformatic methods for analyzing RNA-seq and miRNA-seq data of NSCLC from The Cancer Genome Atlas database. 1352 NSCLC patients and 1320 cancer-free controls for genotyping, and dual luciferase reporter assay, real-time PCR are performed in A549 and H1975 lung cancer cell lines. Results are analyzed by SPSS v16.0. Results: In the present study, we focus on the role of over-expression MIAT in NSCLC. We confirmed that rs1061451 T>C (allele odds ratio = 0.22; P < 0.01) was associated with NSCLC. Furthermore, we constructed MIAT-centric ceRNA network, and three mRNAs (MYO1B, SGK1 and WNT9A) was identified as targets by MIAT via miR-133a-5p. Conclusion: C-containing genotypes of MIAT rs1061451 were protective factor of NSCLC, and MIAT, which may act as ceRNA via miR-133a-5p, modulated MYO1B, SGK1 and WNT9A expression level. Keywords: non-coding RNA, non-small-cell lung cancer, single-nucleotide polymorphism, competing endogenous RNA

Bin Qian,1 Yang Yang,2 Yusheng Yao,3 Yanling Liao,3 Ying Lin3 1Department of Anesthesiology, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China; 2Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; 3Department of Anesthesiology, The Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China Purpose: Sevoflurane preconditioning (SPC) can provide myocardial protective effects similar to ischemic preconditioning. However, the exact mechanism of SPC remains unclear. Previous studies indicate that vascular endothelial growth factor receptor 1 (VEGFR-1) is involved in ischemic preconditioning-mediated cardioprotection. This study was designed to determine the significance of VEGFR-1 signaling in SPC-mediated cardioprotection.Materials and methods: Myocardial ischemia–reperfusion (I/R) rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, after 15 min of baseline equilibration, the isolated hearts were pretreated with 2.5% sevoflurane, 2.5% sevoflurane+MF1 10 µmol/L, or 2.5% sevoflurane+placental growth factor 10 µmol/L, and then subjected to 30 min of global ischemia and 120 min of reperfusion. The changes in hemodynamic parameters, myocardial infarct size, and the levels of creatine kinase-MB, lactate dehydrogenase, cardiac troponin-I, tumor necrosis factor-α, and interleukin 6 in the myocardium were evaluated.Results: Compared to the I/R group, pretreatment with 2.5% sevoflurane significantly improved the cardiac function, limited myocardial infarct size, reduced cardiac enzyme release, upregulated VEGFR-1 expression, and decreased inflammation. In addition, the selective VEGFR-1 agonist, placental growth factor, did not enhance the cardioprotection and anti-inflammation effects of sevoflurane, while the specific VEGFR-1 inhibitor, MF1, completely reversed these effects.Conclusion: Our data have demonstrated that 2.5% sevoflurane preconditioning alleviates heart I/R injury, which is probably mediated by the anti-inflammatory property and upregulation of VEGFR-1. Keywords: sevoflurane, preconditioning, ischemic–reperfusion injury, vascular endothelial growth factor receptor 1, anti-inflammatory

PrBi, a sister member of the rare-earth monopnictide family, is an excellent candidate for studying extreme magnetoresistance and nontrivial topological electronic states. In this study, we perform angular magnetoresistance measurements as well as bulk and surface band structure calculations on this compound. PrBi's magnetoresistance is revealed to be significantly angle-dependent and shows a fourfold symmetry as always observed in the nonmagnetic isostructural counterparts, including LaSb, LaBi, and LuBi. Its angular magnetoresistance can be reproduced well using the semiclassical two-band model. The deduced parameters suggest that PrBi hosts an elongated electron pocket with a mobility anisotropy of ∼3.13 and is slightly uncompensated in its carrier concentration. Our bulk and surface band structure calculations confirm the anisotropic electronic features. Moreover, we reveal that a nodal-line-shaped surface state appears at the X¯ point, and is associated with the quadratic dispersion along the Γ–X¯ direction, and the linear type-I Dirac dispersion along the X¯–M¯ direction. Owing to the type-I Dirac dispersion feature, PrBi could serve as a promising material platform for studying many unexpected physical properties, such as the highly anisotropic transport and valley polarization of electrons. [ABSTRACT FROM AUTHOR]

Abstract Treatment for Parkinson’s disease (PD) has been impeded by inefficient treatment results and multiple membrane barriers during drug delivery. This study reports the design, synthesis, and application of microneedles (MNs) loaded with mitochondrion-targeted liposome encapsulated iron (Fe)-isolated single-atom nanozymes (Mito@Fe-ISAzyme, MFeI), called MFeI MNs, for in situ drug delivery into the brain parenchyma and efficient enrichment of drugs in lesion sites. In in vitro experiments, MFeI can scavenge reactive oxygen species (ROS) and protect the neurons via mitochondrial targeting, guaranteeing the subsequent treatment of PD. Using PD mouse models, we compared the intravenous injection of MFeI with the brain in situ administration of MFeI MNs (in situ MFeI MNs). Results showed that in situ MFeI MNs significantly improved the deep penetration of the drug into brain parenchyma, especially in the vital pathological sites such as the substantia nigra pars compacta and striatum. Importantly, ROS elimination and neuroinflammatory remission in the lesion site were observed, thereby efficiently alleviating the behavioral disorders and pathological symptoms of PD mice. Therefore, the MNs system for in situ single-atom nanozyme liposome delivery exhibits great potential in PD treatment. Graphical abstract

Abstract SATB1, a key regulator of T cell development, governs lineage-specific transcriptional programs upon T cell activation. The absence of SATB1 has been linked to the initiation and progression of autoimmunity. However, its precise roles in this process remain incompletely understood. Here we show that conditional knockout of Satb1 in CD4+ T cells in mice led to T cell hyperactivation and inflammatory cell infiltration across multiple organs. Transcriptional profiling on activated T cells revealed that the loss of SATB1 led to aberrant upregulation of CC chemokines. Treating Satb1 conditional knockout mice with CC chemokine receptor inhibitor alleviated inflammatory cell infiltration. Intriguingly, SATB1’s transcriptional regulation of chemokine genes could not be attributed to its direct binding to chemokine promoters. Instead, SATB1 exerted its regulatory effects by controlling higher-order chromatin organization at a CC chemokine locus. The loss of SATB1 led to the emergence of a new chromatin domain encompassing the Ccl3, Ccl4, Ccl5, Ccl6, and Ccl9 genes and a distal enhancer, resulting in increased contacts between the enhancer and all five chemokine genes, thus inducing their upregulation. Collectively, these results demonstrate that SATB1 protects organs from immune cell infiltration by regulating chemokine expression, providing valuable insights into the development of autoimmunity-related phenotypes.

Abstract The Bin/Amphiphysin/Rvs (BAR) domain protein FAM92A1 is a multifunctional protein engaged in regulating mitochondrial ultrastructure and ciliogenesis, but its physiological role in the brain remains unclear. Here, we show that FAM92A1 is expressed in neurons starting from embryonic development. FAM92A1 knockout in mice results in altered brain morphology and age-associated cognitive deficits, potentially due to neuronal degeneration and disrupted synaptic plasticity. Specifically, FAM92A1 deficiency impairs diverse neuronal membrane morphology, including the mitochondrial inner membrane, myelin sheath, and synapses, indicating its roles in membrane remodeling and maintenance. By determining the crystal structure of the FAM92A1 BAR domain, combined with atomistic molecular dynamics simulations, we uncover that FAM92A1 interacts with phosphoinositide- and cardiolipin-containing membranes to induce lipid-clustering and membrane curvature. Altogether, these findings reveal the physiological role of FAM92A1 in the brain, highlighting its impact on synaptic plasticity and neural function through the regulation of membrane remodeling and endocytic processes.

Objective To explore the efficacy of a novel and simple manual bone cone drilling hematoma drainage for hypertensive intracerebral hemorrhage. Methods From January 2021 to December 2022, 103 patients with hypertensive intracerebral hemorrhage at The Affiliated Bozhou Hospital of Anhui Medical University were included. They were treated with traditional bone cone drilling hematoma drainage (traditional group, n = 51) and novel-type bone cone drilling hematoma drainage (novel-type group, n = 52). Based on pre- and post-surgery head CT results, the hematoma clearance rate and accuracy of catheter placement were calculated. National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of neurological deficits, and modified Rankin Scale (mRS) was used to evaluate the neurological functional prognosis. Results The hematoma clearance rate in the novel-type group [(45.54 ± 24.23)% vs. (35.08 ± 6.49)%; t = 3.008, P = 0.004] and the accuracy of catheter placement [90.38% (47/52) vs. 68.63% (35/51); χ2 = 7.509, P = 0.006] were significantly higher than those of the traditional group. The novel-type group and the traditional group showed statistically significant differences in hematoma volume (F = 9.157, P = 0.003) and mRS score (F = 4.412, P = 0.038). The postoperative hematoma volume (t = - 4.625, P = 0.000) and mRS score (t = - 2.712, P = 0.008) of the novel-type group were lower than those of the traditional group. Statistically significant differences were observed in hematoma volume (F = 280.635, P = 0.000), NIHSS score (F = 443.320, P = 0.000) and mRS score (F = 552.781, P = 0.000) before and after surgery in the 2 groups; the hematoma volume (t = 10.233, P = 0.000; t = 19.906, P = 0.000), NIHSS score (t = 14.576, P = 0.000; t = 15.286, P = 0.000) and mRS score (t = 20.201, P = 0.000; t = 13.511, P = 0.000) after operation were lower than those before operation in the 2 groups. Conclusions The novel and simple manual bone cone drilling hematoma drainage is a safe and effective treatment for hypertensive intracerebral hemorrhage.

BackgroundAs one of the malignant tumors with the highest incidence and fatality in the world, colon adenocarcinoma (COAD) has a very complex pathogenic mechanism, which has not yet been fully elucidated. Ubiquitin can regulate cell proliferation, cell cycle, apoptosis, DNA damage repair, and other processes by changing the activity of substrate proteins or causing ubiquitin-proteasome degradation. These are the key links in the pathogenesis of COAD, and ubiquitin plays an important role in the occurrence and development of COAD.MethodsWe integrated transcriptomics, single-cell and clinical omics, and TCGA and GEO databases of COAD patient data. Cox and Lasso regression was employed to assess ubiquitination genes in COAD for generating ubiquitination-related features. The aim was to evaluate the prognostic value of these features for tumors and their impact on the immune microenvironment. At the same time, the expression level of model genes was further analyzed using single-cell data. Finally, the expression and function of ASNS, a key gene for this trait, were detected in vitro.ResultsIn our study, based on identifiable changes in the expression of marker genes, this feature can be used to classify patients with COAD. Kaplan-Meier survival analysis indicated that those with elevated risk scores in each cohort experienced inferior outcomes. There is good validation in both the training queue and the validation queue. The results of the immune infiltration analysis showed that the immune infiltration rate was significantly increased in the high-risk group. After the knockdown of ASNS, an important gene in the signature, the activity and migration capacity of SW620 and RKO cell lines and colony formation capacity were dramatically reduced in cell tests.ConclusionWe screened ubiquitination-related genes and constructed ubiquitination-related features, which can be used as reliable prognostic indicators of COAD. ASNS was identified as a possible biomarker for COAD.

Summary: The impact of dietary nutrients on tumor immunity remains an area of ongoing investigation, particularly regarding the specific role of vitamins and their mechanism. Here, we demonstrate that vitamin B3 (VB3) induces antitumor immunity against liver cancer through biased GPR109A axis in myeloid cell. Nutritional epidemiology studies suggest that higher VB3 intake reduces liver cancer risk. VB3 supplementation demonstrates antitumor efficacy in multiple mouse models through alleviating the immunosuppressive tumor microenvironment (TME) mediated by tumor-infiltrating myeloid cell, thereby augmenting effectiveness of immunotherapy or targeted therapy in a CD8+ T cell-dependent manner. Mechanically, the TME induces aberrant GPR109A/nuclear factor κB (NF-κB) activation in myeloid cell to shape the immunosuppressive TME. In contrast, VB3 activates β-Arrestin-mediated GPR109A degradation and NF-κB inhibition to suppress the immunosuppressive polarization of myeloid cell, thereby activating the cytotoxic function of CD8+ T cell. Overall, these results expand the understanding of how vitamins regulate the TME, suggesting that dietary VB3 supplementation is an adjunctive treatment for liver cancer.

Lung cancer is the malignant tumor with the highest incidence and mortality rate in China, and surgical resection is a crucial approach for its treatment. In 2023, significant advancements were made in the field of lung cancer surgery. Firstly, CALGB140503 showed that for peripheral ≤2 cm nodular lung cancer, sublobar resection demonstrated no significant difference in survival rates compared to lobectomy, establishing the foundation for its role in early lung cancer treatment. Secondly, JCOG1211 found that segmentectomy could be used to treat 2-3 cm ground-glass opacity-predominant adenocarcinoma, however, patient in this study may undergo overtreatment, which could potentially be mitigated through intraoperative rapid frozen section pathological examination. Furthermore, the ECTOP-1003 study proposed a selective lymph node dissection strategy based on tumor location and intraoperative rapid frozen section pathological examination, achieving a 100% accuracy rate and providing a more precise approach to lymph node dissection. Additionally, the exploration of the cure time window for lung adenocarcinoma was remarkable, emphasizing the importance of timing in surgical intervention to avoid overtreatment in early lung cancer treatment. Finally, the ECTOP-1008 study demonstrated that high-resolution chest computed tomography (CT) scans assisted in determining the pathological invasion degree of lung cancer, aiding in the precise judgment of curative time window. This review summarized the important research progress in the field of lung cancer surgery in 2023, aiming to provide insights for clinical practice and future trials in lung cancer surgery.

Abstract Clustering algorithm is the primary technology used in target clustering and group status analysis which are key features of the Unmanned Aerial Vehicles (UAVs) control system. Due to variable application environment, the stability of the algorithm in the UAVs control system needs to be considered. K‐means clustering is a widely used method in intelligent systems. However, K‐means algorithm is susceptible to the local optimum due to the influence of the initial centroid. For this problem, the predecessors have proposed various effective solutions. These algorithms perform better on real and large‐scale datasets, but they are unable to achieve optimum results with unbalanced datasets. Herein, a simpler and more effective algorithm for seed initialization is proposed, it has a better accuracy rate than the alternative algorithms.Moreover, after running tests multiple times with each algorithm independently, it has the highest stability and the lowest overall volatility. With unbalanced datasets, the proposed algorithm performs significantly better than several other algorithms and therefore can solve the problems that other algorithms have with unbalanced datasets.

Background: Pancreatic cancer (PC), characterized by its aggressive nature and low patient survival rate, remains a challenging malignancy. Anoikis, a process inhibiting the spread of metastatic cancer cells, is closely linked to cancer progression and metastasis through anoikis-related genes. Nonetheless, the precise mechanism of action of these genes in PC remains unclear. Methods: Study data were acquired from the Cancer Genome Atlas (TCGA) database, with validation data accessed at the Gene Expression Omnibus (GEO) database. Differential expression analysis and univariate Cox analysis were performed to determine prognostically relevant differentially expressed genes (DEGs) associated with anoikis. Unsupervised cluster analysis was then employed to categorize cancer samples. Subsequently, a least absolute shrinkage and selection operator (LASSO) Cox regression analysis was conducted on the identified DEGs to establish a clinical prognostic gene signature. Using risk scores derived from this signature, patients with cancer were stratified into high-risk and low-risk groups, with further assessment conducted via survival analysis, immune infiltration analysis, and mutation analysis. External validation data were employed to confirm the findings, and Western blot and immunohistochemistry were utilized to validate risk genes for the clinical prognostic gene signature. Results: A total of 20 prognostic-related DEGs associated with anoikis were obtained. The TCGA dataset revealed two distinct subgroups: cluster 1 and cluster 2. Utilizing the 20 DEGs, a clinical prognostic gene signature comprising two risk genes (CDKN3 and LAMA3) was constructed. Patients with pancreatic adenocarcinoma (PAAD) were classified into high-risk and low-risk groups per their risk scores, with the latter exhibiting a superior survival rate. Statistically significant variation was noted across immune infiltration and mutation levels between the two groups. Validation cohort results were consistent with the initial findings. Additionally, experimental verification confirmed the high expression of CDKN3 and LAMA3 in tumor samples. Conclusion: Our study addresses the gap in understanding the involvement of genes linked to anoikis in PAAD. The clinical prognostic gene signature developed herein accurately stratifies patients with PAAD, contributing to the advancement of precision medicine for these patients.

Ischemic stroke poses a significant global health burden, with rapid revascularization treatments being crucial but often insufficient to mitigate ischemia-reperfusion (I/R) injury. Dexmedetomidine (DEX) has shown promise in reducing cerebral I/R injury, but its potential molecular mechanism, particularly its interaction with non-coding RNAs (ncRNAs), remains unclear. This study investigates DEX’s therapeutic effect and potential molecular mechanisms in reducing cerebral I/R injury. A transient middle cerebral artery obstruction (tMACO) model was established to simulate cerebral I/R injury in adult rats. DEX was administered pre-ischemia and post-reperfusion. RNA sequencing and bioinformatic analyses were performed on the ischemic cerebral cortex to identify differentially expressed non-coding RNAs (ncRNAs) and mRNAs. The sequencing results showed 6,494 differentially expressed (DE) mRNA and 2698 DE circRNA between the sham and tMCAO (I/R) groups. Additionally, 1809 DE lncRNA, 763 DE mRNA, and 2795 DE circRNA were identified between the I/R group and tMCAO + DEX (I/R + DEX) groups. Gene ontology (GO) analysis indicated significant enrichment in multicellular biogenesis, plasma membrane components, and protein binding. KEGG analysis further highlighted the potential mechanism of DEX action in reducing cerebral I/R injury, with hub genes involved in inflammatory pathways. This study demonstrates DEX’s efficacy in reducing cerebral I/R injury and offers insights into its brain-protective effects, especially in ischemic stroke. Further research is warranted to fully understand DEX’s neuroprotective mechanisms and its clinical applications.

Microplastics (MPs) are plastic particles

Alpine wetlands are critical ecosystems for global carbon (C) cycling and climate change mitigation. Ecological restoration projects for alpine grazing wetlands are urgently needed, especially due to their critical role as carbon (C) sinks. However, the fate of the C pool in alpine wetlands after restoration from grazing remains unclear. In this study, soil samples from both grazed and restored wetlands in Zoige (near Hongyuan County, Sichuan Province, China) were collected to analyze soil organic carbon (SOC) fractions, arbuscular mycorrhizal fungi (AMF), soil properties, and plant biomass. Moreover, the Tea Bag Index (TBI) was applied to assess the initial decomposition rate (k) and stabilization factor (S), providing a novel perspective on SOC dynamics. The results of this research revealed that the mineral-associated organic carbon (MAOC) was 1.40 times higher in restored sites compared to grazed sites, although no significant difference in particulate organic carbon (POC) was detected between the two site types. Furthermore, the increased MAOC after restoration exhibited a significant positive correlation with various parameters including S, C and N content, aboveground biomass, WSOC, AMF diversity, and NH4+. This indicates that restoration significantly increases plant primary production, litter turnover, soil characteristics, and AMF diversity, thereby enhancing the C stabilization capacity of alpine wetland soils.