Molecular nitrogen induced structural evolution of single transition metal atoms supported by B/N co-doped graphene for enhanced nitrogen electroreduction performance.

The structural evolution of local coordination environments of single-atom catalysts (SACs) under reaction conditions plays an important role in the catalytic performance of SACs. Using density functional theory calculations, the possible structural evolution of transition metal single atoms supported by B/N codoped-graphene (TM-B2N2/G) under nitrogen reduction reaction (NRR) conditions is explored and the catalytic performance based on reconstructed SACs is theoretically evaluated. A novel nitrogen adsorption mode on TM-B2N2/G is discovered and the protonation of one of the N atoms results in the TM atoms binding with three N atoms, among which one associates with two B atoms (TM-N3B2/G). It is suggested that the N3B2/G supported tungsten single atom (W-N3B2/G) exhibits excellent N2 activity with a limiting potential of -0.27 V and high ammonia selectivity. Electronic structure analysis indicates that the coordination of N3B2/G redistributes the charge density of central W, shifts its d band center upward and strengthens the interaction of W and the adsorbed nitrogen molecule, thereby endowing it with better NRR performance, compared with that supported by pyridine-3N-doped graphene and pyrrolic-3N-doped graphene.

Solution structure of c-FLIP death effector domains.

The formation of death-inducing signaling complex (DISC) and death effector domain (DED) filament initiates extrinsic apoptosis. Recruitment and activation of procaspase-8 at the DISC are regulated by c-FLIP. The interaction between c-FLIP and procaspase-8 is mediated by their tandem DEDs (tDED). However, the structure of c-FLIPtDED and how c-FLIP interferes with procaspase-8 activation at the DISC remain elusive. Here, we solved the monomeric structure of c-FLIPtDED (F114G) at near physiological pH by solution nuclear magnetic resonance (NMR). Structural superimposition reveals c-FLIPtDED (F114G) adopts a structural topology similar to that of procaspase-8tDED. Our results provide a structural basis for understanding how c-FLIP interacts with procaspase-8 and the molecular mechanisms of c-FLIP in regulating cell death.

Expression, purification, and characterization of c-FLIP tandem death effector domains from Escherichia coli.

Cellular FLICE-like inhibitory protein (c-FLIP) regulates extrinsic apoptosis by controlling procaspase-8 activation through its tandem N-terminal death effector domains (DEDs). Here, we present the expression and purification of c-FLIP tandem DEDs (tDED) from Escherichia coli. We observed that the c-FLIPtDED maintains monomeric form under near-physiological pH condition in vitro. Our results also reveal a significant correlation between the pH conditions and the structure of c-FLIPtDED (F114A). The described methods and results would be helpful for follow-up study on the structural and functional of c-FLIP.

Dynamic transcriptome changes during adipose tissue energy expenditure reveal critical roles for long noncoding RNA regulators.

Enhancing brown fat activity and promoting white fat browning are attractive therapeutic strategies for treating obesity and associated metabolic disorders. To provide a comprehensive picture of the gene regulatory network in these processes, we conducted a series of transcriptome studies by RNA sequencing (RNA-seq) and quantified the mRNA and long noncoding RNA (lncRNA) changes during white fat browning (chronic cold exposure, beta-adrenergic agonist treatment, and intense exercise) and brown fat activation or inactivation (acute cold exposure or thermoneutrality, respectively). mRNA-lncRNA coexpression networks revealed dynamically regulated lncRNAs to be largely embedded in nutrient and energy metabolism pathways. We identified a brown adipose tissue-enriched lncRNA, lncBATE10, that was governed by the cAMP-cAMP response element-binding protein (Creb) axis and required for a full brown fat differentiation and white fat browning program. Mechanistically, lncBATE10 can decoy Celf1 from Pgc1α, thereby protecting Pgc1α mRNA from repression by Celf1. Together, these studies provide a comprehensive data framework to interrogate the transcriptomic changes accompanying energy homeostasis transition in adipose tissue.

Structural basis of the mechanism of ß-methyl epimerization by enzyme MarH.

Diverse derivatives of amino acids with different steric configurations are important biosynthetic building blocks. In biology, epimerization is an important way to generate steric diversity. MarH catalyzes the epimerization of the ß-position of (3R)-ß-methyl-indolepyruvate (MeInPy), forming (3S)-ß-MeInPy. Both compounds are derivatives of l-tryptophan (l-Trp) and are important precursors of bioactive natural products. Here, we report the crystal structures of MarH and the NMR structure of its complex with l-Trp, an analogue of its native substrate, (3R)-ß-MeInPy. Structural analysis and mutagenesis studies indicated that His25 acts as a base to remove Hß and generate a planar carbanion intermediate, which is then putatively reprotonated on the opposite face by a water molecule to form (3S)-ß-MeInPy in a stereospecific manner. The details of ß-site isomerization at the atomic level provide deeper insights into the epimerization mechanism of MarH and will facilitate further enzyme design to extend the substrate scope.

MR T2 value of the tibial nerve can be used as a potential non-invasive and quantitative biomarker for the diagnosis of diabetic peripheral neuropathy.

OBJECTIVE: To determine the role of quantitative tibial nerve T2 value in the diagnosis of diabetic peripheral neuropathy (DPN). METHODS: MR imaging and T2 mapping of the tibial nerve were performed in 22 diabetic patients with DPN, 20 diabetic patients without DPN and 20 healthy controls. Nerve T2 values were measured, and compared using the Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic ability of T2 value to identify DPN. RESULTS: Nerve T2 value was 55.06 ± 4.05 ms, 48.91 ± 3.06 ms and 45.61 ± 1.86 ms in patients with DPN, patients without DPN and controls, respectively. Patients with DPN had significantly higher nerve T2 values than patients without DPN (P < 0.001). Nerve T2 values in patients without DPN were higher than in controls (P < 0.001). ROC analysis showed that T2 values had a diagnostic sensitivity of 81.8 %, specificity of 89.2 % and area under the curve of 0.922 for identifying patients with DPN from patients without DPN plus controls when the cutoff point was 51.34 ms. CONCLUSION: T2 value of the tibial nerve can be used as an alternative, non-invasive quantitative parameter to assess DPN in diabetic patients. KEY POINTS: • Tibial nerves in patients with DPN showed T2 hyperintensity and enlargement. • Tibial nerves in patients with DPN had an increased T2 value. • T2 value might be used as a quantitative biomarker for DPN.

A KSHV microRNA Directly Targets G Protein-Coupled Receptor Kinase 2 to Promote the Migration and Invasion of Endothelial Cells by Inducing CXCR2 and Activating AKT Signaling.

Kaposi's sarcoma (KS) is a highly disseminated angiogenic tumor of endothelial cells linked to infection by Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV encodes more than two dozens of miRNAs but their roles in KSHV-induced tumor dissemination and metastasis remain unknown. Here, we found that ectopic expression of miR-K12-3 (miR-K3) promoted endothelial cell migration and invasion. Bioinformatics and luciferase reporter analyses showed that miR-K3 directly targeted G protein-coupled receptor (GPCR) kinase 2 (GRK2, official gene symbol ADRBK1). Importantly, overexpression of GRK2 reversed miR-K3 induction of cell migration and invasion. Furthermore, the chemokine receptor CXCR2, which was negatively regulated by GRK2, was upregulated in miR-K3-transduced endothelial cells. Knock down of CXCR2 abolished miR-K3-induced cell migration and invasion. Moreover, miR-K3 downregulation of GRK2 relieved its direct inhibitory effect on AKT. Both CXCR2 induction and the release of AKT from GRK2 were required for miR-K3 maximum activation of AKT and induction of cell migration and invasion. Finally, deletion of miR-K3 from the KSHV genome abrogated its effect on the GRK2/CXCR2/AKT pathway and KSHV-induced migration and invasion. Our data provide the first-line evidence that, by repressing GRK2, miR-K3 facilitates cell migration and invasion via activation of CXCR2/AKT signaling, which likely contribute to the dissemination of KSHV-induced tumors.

Research progress of long noncoding RNA in China.

RNA is essential for all kingdoms of life and exerts important functions beyond transferring genetic information from DNA to protein. With the advent of the state-of-the-art deep sequencing technology, a large portion of noncoding transcripts in eukaryotic genomes has been broadly identified. Among them, long noncoding RNAs (lncRNAs) have been emerged as a new class of RNA molecules that have regulatory potential in a variety of physiological and pathological processes. Here we summarize recent research progresses that have been made by scientists in China on lncRNAs, including their biogenesis, functional implication and the underlying mechanism of action at the current stage. © 2016 IUBMB Life, 68(11):887-893, 2016.

Genomewide mapping and screening of Kaposi's sarcoma-associated herpesvirus (KSHV) 3' untranslated regions identify bicistronic and polycistronic viral transcripts as frequent targets of KSHV microRNAs.

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes over 90 genes and 25 microRNAs (miRNAs). The KSHV life cycle is tightly regulated to ensure persistent infection in the host. In particular, miRNAs, which primarily exert their effects by binding to the 3' untranslated regions (3'UTRs) of target transcripts, have recently emerged as key regulators of KSHV life cycle. Although studies with RNA cross-linking immunoprecipitation approach have identified numerous targets of KSHV miRNAs, few of these targets are of viral origin because most KSHV 3'UTRs have not been characterized. Thus, the extents of viral genes targeted by KSHV miRNAs remain elusive. Here, we report the mapping of the 3'UTRs of 74 KSHV genes and the effects of KSHV miRNAs on the control of these 3'UTR-mediated gene expressions. This analysis reveals new bicistronic and polycistronic transcripts of KSHV genes. Due to the 5'-distal open reading frames (ORFs), KSHV bicistronic or polycistronic transcripts have significantly longer 3'UTRs than do KSHV monocistronic transcripts. Furthermore, screening of the 3'UTR reporters has identified 28 potential new targets of KSHV miRNAs, of which 11 (39%) are bicistronic or polycistronic transcripts. Reporter mutagenesis demonstrates that miR-K3 specifically targets ORF31-33 transcripts at the lytic locus via two binding sites in the ORF33 coding region, whereas miR-K10a-3p and miR-K10b-3p and their variants target ORF71-73 transcripts at the latent locus through distinct binding sites in both 5'-distal ORFs and intergenic regions. Our results indicate that KSHV miRNAs frequently target the 5'-distal coding regions of bicistronic or polycistronic transcripts and highlight the unique features of KSHV miRNAs in regulating gene expression and life cycle.

KSHV microRNAs mediate cellular transformation and tumorigenesis by redundantly targeting cell growth and survival pathways.

Kaposi's sarcoma-associated herpesvirus (KSHV) is causally linked to several human cancers, including Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease, malignancies commonly found in HIV-infected patients. While KSHV encodes diverse functional products, its mechanism of oncogenesis remains unknown. In this study, we determined the roles KSHV microRNAs (miRs) in cellular transformation and tumorigenesis using a recently developed KSHV-induced cellular transformation system of primary rat mesenchymal precursor cells. A mutant with a cluster of 10 precursor miRs (pre-miRs) deleted failed to transform primary cells, and instead, caused cell cycle arrest and apoptosis. Remarkably, the oncogenicity of the mutant virus was fully restored by genetic complementation with the miR cluster or several individual pre-miRs, which rescued cell cycle progression and inhibited apoptosis in part by redundantly targeting IκBα and the NF-κB pathway. Genomic analysis identified common targets of KSHV miRs in diverse pathways with several cancer-related pathways preferentially targeted. These works define for the first time an essential viral determinant for KSHV-induced oncogenesis and identify NF-κB as a critical pathway targeted by the viral miRs. Our results illustrate a common theme of shared functions with hierarchical order among the KSHV miRs.

New meroterpenoids from the endophytic fungus Aspergillus flavipes AIL8 derived from the mangrove plant Acanthus ilicifolius.

Four new meroterpenoids (2-5), along with three known analogues (1, 6, and 7) were isolated from mangrove plant Acanthus ilicifolius derived endophytic fungus Aspergillus flavipes. The structures of these compounds were elucidated by NMR and MS analysis, the configurations were assigned by CD data, and the stereochemistry of 1 was confirmed by X-ray crystallography analysis. A possible biogenetic pathway of compounds 1-7 was also proposed. All compounds were evaluated for antibacterial and cytotoxic activities.

Effects of climate and geochemical properties on the chemical forms of soil Cd, Pb and Cr along a more than 4000 km transect.

Soil heavy metal speciation has received much attention for their different ecological and environmental effects. However, the effects of climate and soil geochemical properties on them in uncontaminated soils at macroscale were still unclear. Therefore, a transect more than 4000 km was chosen to study the effects of these factors on soil Cd, Pb and Cr forms. The results revealed that mean annual temperature and precipitation showed significant positive relations with the exchangeable and Fe-Mn oxide bound states of Cd, Pb and Cr, and residual Cr. And humidity and drought indexes were significantly positively correlated with their organic and carbonate bound forms, respectively. As for soil geochemical properties, pH displayed significant negative relationships with exchangeable, Fe-Mn oxide and organic bound Pb and Cr, and exchangeable Cd. Fe2O3 was significantly positively with the exchangeable and Fe-Mn oxide bound Cd, Pb and Cr, and residual Cr. And soil organic matter showed positive relations with organic bound Pb and Cr, and residual Cd and Cr, displayed negative relationships with carbonated bound Pb and Cr. Overall, climate and soil geochemical properties together affect the transformation and transport of heavy metals between different forms in uncontaminated soils.

A Kaposi's sarcoma-associated herpesvirus microRNA and its variants target the transforming growth factor ß pathway to promote cell survival.

Transforming growth factor ß (TGF-ß) signaling regulates cell growth and survival. Dysregulation of the TGF-ß pathway is common in viral infection and cancer. Latent infection by Kaposi's sarcoma-associated herpesvirus (KSHV) is required for the development of several AIDS-related malignancies, including Kaposi's sarcoma and primary effusion lymphoma (PEL). KSHV encodes more than two dozen microRNAs (miRs) derived from 12 pre-miRs with largely unknown functions. In this study, we show that miR variants processed from pre-miR-K10 are expressed in KSHV-infected PEL cells and endothelial cells, while cellular miR-142-3p and its variant miR-142-3p_-1_5, which share the same seed sequence with miR-K10a_ +1_5, are expressed only in PEL cells and not in uninfected and KSHV-infected TIME cells. KSHV miR-K10 variants inhibit TGF-ß signaling by targeting TGF-ß type II receptor (TßRII). Computational and reporter mutagenesis analyses identified three functional target sites in the TßRII 3' untranslated region (3'UTR). Expression of miR-K10 variants is sufficient to inhibit TGF-ß-induced cell apoptosis. A suppressor of the miRs sensitizes latent KSHV-infected PEL cells to TGF-ß and induces apoptosis. These results indicate that miR-K10 variants manipulate the TGF-ß pathway to confer cells with resistance to the growth-inhibitory effect of TGF-ß. Thus, KSHV miRs might target the tumor-suppressive TGF-ß pathway to promote viral latency and contribute to malignant cellular transformation.

Aptamer modified Zr-based porphyrinic nanoscale metal-organic frameworks for active-targeted chemo-photodynamic therapy of tumors.

Active-targeted nanoplatforms could specifically target tumors compared to normal cells, making them a promising therapeutic agent. The aptamer is a kind of short DNA or RNA sequence that can specifically bind to target molecules, and could be widely used as the active targeting agents of nanoplatforms to achieve active-targeted therapy of tumors. Herein, an aptamer modified nanoplatform DOX@PCN@Apt-M was designed for active-targeted chemo-photodynamic therapy of tumors. Zr-based porphyrinic nanoscale metal organic framework PCN-224 was synthesized through a one-pot reaction, which could produce cytotoxic 1O2 for efficient treatment of tumor cells. To improve the therapeutic effect of the tumor, the anticancer drug doxorubicin (DOX) was loaded into PCN-224 to form DOX@PCN-224 for tumor combination therapy. Active-targeted combination therapy achieved by modifying the MUC1 aptamer (Apt-M) onto DOX@PCN-224 surface can not only further reduce the dosage of therapeutic agents, but also reduce their toxic and side effects on normal tissues. In vitro, experimental results indicated that DOX@PCN@Apt-M exhibited enhanced combined therapeutic effect and active targeting efficiency under 808 nm laser irradiation for MCF-7 tumor cells. Based on PCN-224 nanocarriers and aptamer MUC1, this work provides a novel strategy for precisely targeting MCF-7 tumor cells.

A cluster of transcripts encoded by KSHV ORF30-33 gene locus.

Kaposi's sarcoma-associated herpesvirus ORF30-33 locus encodes four genes with unknown functions. We performed transcriptional mapping of these genes. Northern-hybridization, 5'- and 3'-rapid amplification of cDNA ends, and DNA sequencing identified four transcripts of 3.7, 3.6, 2.7, and 1.4 kb, none of which has alternative splicing. While all transcripts have the same termination site, their start sites vary. All transcripts are not expressed or only weakly expressed in latent cells but can be chemically induced. The 3.7 and 3.6 kb transcripts contain all four genes and are sensitive to cycloheximide (CH) but resistant to phosphonoacetic acid (PAA), indicating that they are early lytic transcripts. The 2.7 kb transcript contains ORF32 and ORF33 genes while the 1.4 kb transcript contains the ORF33 gene. Both transcripts are sensitive to CH and PAA, indicating that they are late lytic transcripts. Furthermore, we identified four promoters with functional TATA boxes, none of which is directly transactivated by RTA. Examination of the 5' untranslated region of ORF31 failed to identify any functional internal ribosome entry sites. These results define the transcriptional patterns of the ORF30-33 locus, which should help the delineation of its function.

Association Between Muscle Morphology Changes, Cervical Spine Degeneration, and Clinical Features in Patients with Chronic Nonspecific Neck Pain: A Magnetic Resonance Imaging Analysis.

OBJECTIVE: The primary objective of the present study was to investigate the correlations among cervical paraspinal muscle morphology changes (fatty infiltration [FI] and muscle atrophy), cervical degeneration, and clinical features in patients with chronic nonspecific neck pain (CNSNP). METHODS: The magnetic resonance imaging data for 55 consecutive patients (average age, 35.80 years) with CNSNP were analyzed in the present cross-sectional study. The muscle morphology changes in 7 groups of paraspinal muscles, indicated by the adjusted cross-sectional area (aCSA) and FI ratio (FI%), were measured from C3/4 to C6/7. The correlations of these changes with disc degeneration, cervical balance (C2-C7 angle and cervical alignment), and clinical features (severity of neck pain and related disability and frequency of acute neck pain recurrence) were evaluated. RESULTS: Significant correlations between FI% and aCSA and the grade of disc degeneration were observed in specific muscle groups at each level (P < 0.05). Morphological changes in the deep extensors and superficial paraspinal muscles were significantly associated with the cervical balance parameters (P < 0.05). The FI% showed a significant positive correlation, and the aCSA showed a significant negative correlation with the severity of neck pain and related disability (P < 0.05). Correlations between the morphological changes and the frequency of acute neck pain recurrence were also present in specific muscles (P < 0.05). CONCLUSIONS: Correlations among the muscle morphology changes, cervical degeneration, and clinical features were established for patients with CNSNP. Muscle volume changes and FI might affect CNSNP diversely through different paraspinal muscle groups. These results imply a complex contribution of muscle morphological changes to cervical degeneration and the clinical course of CNSNP.

ADC and kinetic parameter of primary tumor: Surrogate imaging markers for fertility-sparing vaginal radical trachelectomy in patients with stage IB cervical cancer.

PURPOSE: To investigate the role of ADC and kinetic parameters derived from DCE-MRI in selecting eligible candidates for fertility-sparing vaginal radical trachelectomy (VRT). METHOD: Female patients with FIGO stage IB cervical cancers between March 2019 and January 2022 were retrospectively included. All patients underwent hysterectomy and bilateral lymphadenectomy. According to the surgical pathology, the study population was divided into VRT-eligible group and VRT-ineligible group. ADC, semi-quantitative and quantitative kinetic parameters of the primary tumor were compared between the two groups. Logistic regression analysis was used to determine the independent predictors for VRT eligibility and ROC curve was used to evaluate the predictive performance. RESULTS: 19 patients were deemed eligible for VRT and 50 were ineligible. Compared with VRT-eligible group, time to peak and ADC were significantly lower in VRT-ineligible group (P = 0.004 and 0.001, respectively) while volume fraction of plasma (Vp) was higher in VRT ineligible group (P = 0.001). ADC and Vp were independent predictors for VRT eligibility. Combining Vp and ADC yielded the highest area under the ROC curve of 0.853 compared with that of 0.766 for Vp and 0.764 for ADC, though marginal differences were found (P = 0.109 and 0.078, respectively). CONCLUSIONS: ADC and the kinetic DCE-MRI parameter Vp can be used as surrogate markers to select eligible candidates for fertility-sparing VRT.

The Effects of Age, Period, and Cohort on the Mortality of Cervical Cancer in Three High-Income Countries: Canada, Korea, and Italy.

BACKGROUND: As the second most common gynecologic cancer worldwide, cervical cancer has led to morbidity and mortality in thousands of women. Our study is aimed at comparing the long-term trends of mortality rates for cervical cancer in three high-income countries-Canada, Korea, and Italy-and analyzing the detached effects of chronological age, time period, and birth cohort by age-period-cohort (APC) analysis. METHODS: Joinpoint regression was used in this study, and the age-period-cohort model combined with the intrinsic estimator method was also applied to estimate the detached effect of each age, time period, and birth cohort on cervical cancer mortality. RESULTS: For the overall trends of ASMRs for cervical cancer, the rates for Canada and Italy generally decreased during the whole observation periods while the rate for Korea exhibited a significant increase from 1986 to 2003. The APC analysis suggested that the cancer mortality risks consistently increased with age in the age groups including women aged 20 to 50 years in all areas. The period effect exhibited a general upward trend for both Korea and Italy, while a decreased trend was observed for Canada during the whole observation period. The mortality risk generally decreased with birth cohort, except there was a slight increase for younger generations in the three countries. CONCLUSIONS: Our study shows that the overall decrease in the cohort effect may have contributed to the reduced mortality rate for Italy and Canada, and the increased period effects and cohort effect in younger generations may have led to the increase in cancer mortality rate for Korea.

Quantitative kinetic parameters of primary tumor can be used to predict pelvic lymph node metastasis in early-stage cervical cancer.

PURPOSE: To investigate the role of kinetic parameters of primary tumor derived from dynamic contrast-enhanced MRI (DCE-MRI) in predicting pelvic lymph node metastasis (PLNM) in patients with cervical cancer. METHODS: 66 women with newly diagnosed cervical cancer were included between July 2017 and August 2019. All patients had a FIGO stage IB-IIA cancer and treated with hysterectomy and bilateral lymphadenectomy. Kinetic parameters of the primary tumor were derived from DCE-MRI data. The tumor diameter, ADC value, kinetic parameters, and nodal short-axis diameter were compared between patients with or without PLNM. Logistic regression analysis was used to determine the independent predictors for PLNM and receiver operator characteristic curve was used to evaluate the predictive performance. RESULTS: There were 20 patients with PLNM and 46 patients without PLNM. Tumor diameter, the efflux rate constant (Kep), and nodal short-axis diameter were significantly higher in patients with PLNM (P < 0.01). Multivariate logistic regression analysis showed that Kep and short-axis diameter were independent predictors for PLNM. Combining Kep and nodal short-axis diameter yielded the highest area under the curve (AUC) of 0.839. Combined with Kep, the sensitivity, specificity, negative predictive value, and positive predictive value of nodal short-axis diameter increased from 0.500, 0.957, 0.815, and 0.833 to 0.600, 0.978, 0.923, and 0.849, respectively. With 1.113 min-1 as threshold, the sensitivity and specificity values of Kep in predicting PLNM in patients with normal-sized lymph nodes were 0.909 and 0.667, respectively. CONCLUSIONS: Kep of primary tumor can be used as a surrogate marker to predict PLNM in cervical cancer.

Dynamic network topological properties for classifying primary dysmenorrhoea in the pain-free phase.

BACKGROUND: Primary dysmenorrhoea (PDM) is known to alter brain static functional activity. This study aimed to explore the dynamic topological properties (DTP) of dynamic brain functional network in women with PDM in the pain-free phase and their performance in distinguishing PDM in the pain-free phase from healthy controls. METHODS: Thirty-five women with PDM and 38 healthy women without PDM were included. A dynamic brain functional network was constructed using the slide-window approach. The stability (TP-Stab) and variability (TP-Var) of the DTP of the dynamic functional network were computed using the graph-theory method. A support vector machine (SVM) was used to evaluate the performance of DTP in identifying PDM in the pain-free phase. RESULTS: Compared with healthy controls, women with PDM had not only lower TP-Stab in global DTP, which included cluster clustering coefficient (Cp ), characteristic path length (Lp ), global efficiency (Eg ) and local efficiency (Eloc ), but also lower TP-Stab and higher TP-Var in nodal DTP (nodal efficiency, Enod ), mainly in the prefrontal cortex, anterior cingulate cortex, parahippocampal regions and insula. The TP-Stab and TP-Var were significantly correlated with psychological variables, that is positive emotions, sense of control and meaningful existence. SVM analysis showed that the DTP could identify PDM in the pain-free phase from healthy controls with an accuracy of 79.31%, sensitivity of 82.61% and specificity of 76%. CONCLUSIONS: Women with PDM in the pain-free phase have altered global DTP and nodal DTP, mainly involving pain-related neurocircuits. The highly variable brain network is helpful for identifying PDM in the pain-free phase. SIGNIFICANCE: This study shows that women with primary dysmenorrhoea (PDM) have decreased stability of dynamic network topological properties (DTP) and increased DTP variability in the pain-free phase. The altered DTP can be used to identify PDM in the pain-free phase. These findings demonstrate the presence of unstable characteristics in the whole network and disrupted pain-related neurocircuits, which might be used as potential classifiers for PDM in the pain-free phase. This study improves our knowledge of the brain mechanisms underlying PDM.