[摘 要] 目的：探究着丝粒蛋白M（CENPM）在脑胶质瘤中的表达特征、临床预后价值及其对肿瘤恶性生物学行为的调控机制，为脑胶质瘤的精准治疗提供潜在靶点。方法：基于中国胶质瘤基因组图谱（CGGA）和癌症基因组图谱（TCGA）数据库分析CENPM在胶质瘤中的表达及其与患者临床病理特征和预后的相关性。通过基因本体论（GO）分析、京都基因与基因组百科全书（KEGG）富集分析和单细胞转录组分析探索CENPM的生物学功能和作用机制。WB法检测CENPM在胶质瘤细胞（LN-18、LN-229、U-138MG、U-251MG）和正常胶质细胞（HEB）中的表达；构建CENPM敲低细胞后，通过CCK-8、集落形成、Transwell和划痕实验评估恶性表型改变。结果：CENPM在WHO高级别胶质瘤中呈高表达（P < 0.05），与肿瘤恶性程度正相关。高表达组患者总体生存期显著短于低表达组（P < 0.01），Cox回归证实CENPM是影响胶质瘤患者预后的独立危险因素（P < 0.05）。功能富集分析结果显示CENPM相关基因主要富集于细胞周期调控、PI3K-Akt通路和免疫相关过程。单细胞分析结果显示CENPM主要在CD8⁺ T细胞高表达，并通过PTN-PTPRZ1/NCL配受体调控细胞通信。体外实验证实CENPM在胶质瘤细胞表达高于正常胶质细胞（LN-18：P < 0.01，LN-299：P < 0.05）；敲低CENPM显著抑制迁移（P < 0.05），但增强集落形成，提示其在肿瘤进展中的双重调控作用。结论：CENPM作为胶质瘤独立预后危险因子，通过调控细胞周期、PTN通路和免疫微环境驱动肿瘤进展，其差异化调控机制（抑制迁移、促进增殖）具有潜在的临床转化价值，可作为分子分型和靶向治疗候选标志物。

Objective To analyze the correlation between serum cystatin C (Cys-C) and bone turnover markers in elderly patients with type 2 diabetes mellitus (T2DM) and osteoporosis. Methods A retrospective analysis was conducted on the data of 320 elderly patients with T2DM admitted to Huai'an First People's Hospital from August 2021 to June 2024. Patients were divided into the osteoporosis group and the non-osteoporosis group according to whether they had osteoporosis. General information, bone turnover markers, and serum Cys-C levels were collected from all patients. The data were compared between the two groups to analyze the influencing factors of osteoporosis in elderly patients with T2DM and the correlation between serum Cys-C and bone turnover markers. Results The levels of total cholesterol and LDL-C in the osteoporosis group were higher than those in the non-osteoporosis group, and the bone mineral density was lower than that in the non-osteoporosis group (P<0.05). The levels of TPINP, β-CTX, and Cys-C in the osteoporosis group were higher than those in the non-osteoporosis group, and 25-OH-D3 level was lower than that in the non-osteoporosis group (P<0.05). Serum Cys-C was positively correlated with TPINP and β-CTX, and negatively correlated with 25-OH-D₃ (P<0.05). Multivariate logistic regression analysis found that total cholesterol, LDL-C, TPINP, β-CTX, 25-OH-D₃, and Cys-C were factors influencing osteoporosis in elderly patients with T2DM (P<0.05). Conclusion Serum Cys-C levels in elderly patients with T2DM and osteoporosis are elevated. There is a significant correlation between Cys-C level and bone turnover markers.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

Heart failure （HF）， as the terminal stage of most cardiovascular diseases， manifests with primary symptoms including dyspnea， fatigue， edema， and palpitations. With recurrent episodes and a protracted clinical course， HF imposes a substantial global disease burden. PANoptosis represents a distinctive form of programmed cell death （PCD） that integrates features of pyroptosis， apoptosis， and necroptosis， yet cannot be fully attributed to any single pathway among these three PCD modalities. Recent studies demonstrate significant dysregulation of PANoptosis-related genes during HF progression， positioning PANoptosis as both an emerging mechanism mediating HF pathogenesis and a novel therapeutic target. In recent years， traditional Chinese medicine （TCM） has gained substantial recognition for its therapeutic potential in HF management， offering advantages such as flexible compatibility， multi-target effects， and minimal adverse reactions. Astragali Radix， a representative Qi-invigorating and blood-activating herbal medicine， has demonstrated remarkable clinical efficacy in the treatment for various HF subtypes. Research reveals that its major bioactive components—including astragaloside Ⅳ， polysaccharide， quercetin， and calycosin—exhibit significant associations with the regulation of apoptosis， pyroptosis， and necroptosis pathways. This review systematically explores the therapeutic feasibility of Astragali Radix in the prevention and treatment of HF through the lens of PANoptosis mechanisms. By synthesizing recent advances in the mechanisms of Astragali Radix-derived bioactive compounds and Astragali Radix-containing compound prescriptions in modulating PANoptosis， this paper aim to provide critical insights for advancing the diagnosis and therapeutic strategies of HF.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

Heart failure （HF）， as the terminal stage of most cardiovascular diseases， manifests with primary symptoms including dyspnea， fatigue， edema， and palpitations. With recurrent episodes and a protracted clinical course， HF imposes a substantial global disease burden. PANoptosis represents a distinctive form of programmed cell death （PCD） that integrates features of pyroptosis， apoptosis， and necroptosis， yet cannot be fully attributed to any single pathway among these three PCD modalities. Recent studies demonstrate significant dysregulation of PANoptosis-related genes during HF progression， positioning PANoptosis as both an emerging mechanism mediating HF pathogenesis and a novel therapeutic target. In recent years， traditional Chinese medicine （TCM） has gained substantial recognition for its therapeutic potential in HF management， offering advantages such as flexible compatibility， multi-target effects， and minimal adverse reactions. Astragali Radix， a representative Qi-invigorating and blood-activating herbal medicine， has demonstrated remarkable clinical efficacy in the treatment for various HF subtypes. Research reveals that its major bioactive components—including astragaloside Ⅳ， polysaccharide， quercetin， and calycosin—exhibit significant associations with the regulation of apoptosis， pyroptosis， and necroptosis pathways. This review systematically explores the therapeutic feasibility of Astragali Radix in the prevention and treatment of HF through the lens of PANoptosis mechanisms. By synthesizing recent advances in the mechanisms of Astragali Radix-derived bioactive compounds and Astragali Radix-containing compound prescriptions in modulating PANoptosis， this paper aim to provide critical insights for advancing the diagnosis and therapeutic strategies of HF.

ObjectiveThe U6 promoter is an essential element for driving sgRNA expression in the clustered regularly interspaced short palindromic repeat sequences/CRISPR-associated protein 9（CRISPR/Cas9）gene editing system in dicotyledonous plants. Endogenous U6 promoters typically exhibit higher transcriptional activity， which can significantly improve gene editing efficiency. This study aims to identify endogenous U6 promoters in Artemisia annua to optimize its CRISPR/Cas9 gene editing system， which holds significant importance for its molecular breeding. MethodsOn the basis of the highly conserved U6 snRNA sequences in Arabidopsis thaliana， endogenous U6 promoters were screened in the A. annua genome. Expression vectors were constructed with candidate AaU6 promoter driving the firefly luciferase （LUC） reporter gene， and then transiently transformed into Nicotiana benthamiana. Transcriptional activities of the promoters were measured and compared by in vivo imaging and the Dual Luciferase Reporter assay. ResultsEight endogenous U6 promoters were successfully cloned from A. annua. Sequences alignment revealed that all these promoters contained the two conserved cis-acting elements， upstream sequence element （USE） and TATA-box， which affected their transcriptional activity. Dual-luciferase activity assays indicated that the transcriptional activities of AaU6-3， AaU6-1， and AaU6-5 were significantly higher than that of the Arabidopsis AtU6-26 promoter， with AaU6-3 exhibiting the highest activity. ConclusionThis study identified three endogenous AaU6 promoters with high transcriptional activity in A. annua， providing key functional elements for establishing an efficient gene editing system in A. annua. These findings will contribute to advancing precision molecular breeding and high-quality germplasm innovation in A. annua.

Antibiotic resistance is spreading at a faster rate than new antibiotic agents applied for clinical remedies. It is an urgent need to discover potential compounds to combat multidrug-resistant (MDR) bacteria. Marine fungi offer a promising avenue for mining antibiotic-like molecules with chemical diversity. To discover structurally novel and antibiotic metabolites, we screened the in-house marine fungus genome library and found a fungus Stephanonectria keithii LZD-10-1 containing a non-ribosomal peptide synthetase (NRPS) cluster with 18 modules to synthesize a new subfamily of peptaibols with effective eradication against MDR pathogens. Targeting isolation of the cultured fungus afforded six new peptaibols, which exhibit the ability to kill MDR bacteria by targeting bacterial membrane phospholipids, especially phosphatidylglycerol (PG), leading to the dysfunction of bacterial membranes. Furthermore, their efficacies against methicillin-resistant Staphylococcus aureus (MRSA) in both Galleria mellonella and mouse wound infection models were observed. This study underscores the significance of employing genome-guided approaches to identify untapped marine fungi as potential sources for novel antibiotic candidates with unique scaffolds.

OBJECTIVES: To analyze the differential expression and biological functions of circRNAs in the anterior lens capsules of high myopic patients with cataract and their pathogenic roles in the development of this condition. METHODS: Anterior lens capsule specimens were collected intraoperatively from 36 patients with age-related cataract (ARC) and 36 high myopic patients with cataract. Among these, 18 specimens from each group were selected for whole transcriptome sequencing and biological analysis, and the remaining 36 specimens were used for validation of circPDGFRA, circFOXJ3, hsa_circ_0004767, hsa_circ_0007528, ciCRIM1, circMAN1A2, circSLC5A3, and circPTK2 expressions using RT-qPCR. hsa_circ_0007528 was selected for cell experiments to examine its effects on proliferation, migration, and apoptosis of lens epithelial cells (LECs). RESULTS: A total of 16 192 circRNAs were detected in the specimens from both groups, among which 62 circRNAs were differentially expressed (29 upregulated and 33 downregulated). GO and KEGG analyses revealed that the differentially expressed circRNAs were primarily localized in the cytoplasm, nucleoplasm, and endoplasmic reticulum, and were involved in signaling pathways associated with Gap junction and the PI3K-Akt, NF-κB, Jak-STAT, HIF-1, and MAPK signaling pathways. The ceRNA network predicted multiple target genes. RT-qPCR validation results were consistent with the sequencing data. In the LECs, upregulation of hsa_circ_0007528 significantly inhibited cell proliferation and migration and obviously promoted cell apoptosis. CONCLUSIONS The expression profile of circRNAs in the anterior lens capsule of high myopic patients with cataract differs from that of ARC patients. Upregulation of hsa_circ_0007528 inhibits LEC proliferation and migration and promotes cell apoptosis.
Humans ; Cataract/complications* ; RNA, Circular ; Myopia/genetics* ; Apoptosis ; Cell Proliferation ; Epithelial Cells ; Cell Movement ; Anterior Capsule of the Lens/metabolism* ; Male ; Female

Objective:To explore the clinical features and genetic etiology of a child with a SETD1B gene variant causing seizures and language delay. Methods:A child with a SETD1B gene variant admitted to the Department of Pediatric Neurology at the Third Affiliated Hospital of Zhengzhou University in September 2022 was selected as the study subject. Clinical data of the child were collected, and peripheral blood samples from the child and her parents were obtained. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variant. Using " SETD1B" and " epilepsy" as the Chinese and English keywords, relevant cases were retrieved from databases including CNKI, Wanfang Data, OMIM and PubMed, with the search period spanning from database inception to June 2024. Results:① The child was a 6-year-old female presenting with myoclonic seizures accompanied by global developmental delay. ② WES and Sanger sequencing revealed that the child has carried a de novo SETD1B gene variant, namely, c. 5582G>A (p.Cys1961Tyr). According to the American College of Medical Genetics and Genomics (ACMG) guidelines for sequence variant interpretation, this variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). ③ The child was not controlled with effective doses of valproate, levetiracetam, or clonazepam but was successfully managed with low-dose lamotrigine. Follow-up electroencephalography showed normal results, and developmental progress gradually improved. ④ A total of 37 epilepsy cases with SETD1B gene variants were reported across six studies. The predominant seizure types included absence seizures and myoclonic absence seizures, accompanied by delayed language development. The response to pharmacological treatment was generally poor, with no statistically significant difference in incidence between males and females. Conclusion:SETD1B gene variant may induced neurological disorders with drug-resistant epilepsy and severe clinical manifestations. Lamotrigine is effective in controlling the epileptic seizures.