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Histone lysine methyltransferases (HKMTs) deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression. The structures and functions of HKMTs have been extensively investigated in recent decades, significantly advancing our understanding of the dynamic regulation of histone methylation. Here, we review the recent progress in structural studies of representative HKMTs in complex with nucleosomes (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases), with emphasis on the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these HKMTs. These structural studies inform HKMTs’ roles in tumorigenesis and provide the foundations for developing new therapeutic approaches targeting HKMTs in cancers.

Previous studies on the diagnostic value of arterial calcium stimulation with hepatic venous sampling (ASVS) for the localization of insulinoma have reported inconsistent results. Here, we performed a meta-analysis of the relevant published studies. PubMed, Embase, Web of Science, the Cochrane Library, and Wanfang Data were searched for studies on the diagnostic value of ASVS in insulinoma localization published up to May 2019. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and receiver operating characteristic (ROC) curve of ASVS in the localization of insulinoma. We included ten studies involving 337 patients in the study. The pooled sensitivity, specificity, PLR, and NLR were 0.93 (95% confidence interval [CI]: 0.83-0.97), 0.86 (95%CI: 0.75-0.93), 6.8(95%CI: 3.7-12.7), and 0.08 (95%CI: 0.03-0.19), respectively. The DOR was 84 (95%CI: 30-233), and the area under the ROC curve was 0.96 (95%CI: 0.94-0.97).The results of the heterogeneity of the studies (P = 0.00, I2 = 80.17) were calculated using forest plots of the DOR. ASVS is of significant value in localization of insulinoma. If a qualitative diagnosis of insulinoma is definite and the imaging examination results are negative, ASVS should be performed to confirm the localization of insulinoma.

The development of sensitive and versatile techniques to detect protein-protein interactions in vivo is important for understanding protein functions. The previously described techniques, fluorescence resonance energy transfer and bimolecular fluorescence complementation, which are used widely for protein-protein interaction studies in plants, require extensive instrumentation. To facilitate protein-protein interaction studies in plants, we adopted the luciferase complementation imaging assay. The amino-terminal and carboxyl-terminal halves of the firefly luciferase reconstitute active luciferase enzyme only when fused to two interacting proteins, and that can be visualized with a low-light imaging system. A series of plasmid constructs were made to enable the transient expression of fusion proteins or generation of stable transgenic plants. We tested nine pairs of proteins known to interact in plants, including Pseudomonas syringae bacterial effector proteins and their protein targets in the plant, proteins of the SKP1-Cullin-F-box protein E3 ligase complex, the HSP90 chaperone complex, components of disease resistance protein complex, and transcription factors. In each case, strong luciferase complementation was observed for positive interactions. Mutants that are known to compromise protein-protein interactions showed little or much reduced luciferase activity. Thus, the assay is simple, reliable, and quantitative in detection of protein-protein interactions in plants.

Background Previous studies have shown inconsistent results about the usefulness of bilateral inferior petrosal sinus sampling (BIPSS) in differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome. This meta-analysis evaluated the diagnostic value of BIPSS via the published literature. Methods This study searched PubMed, Embase, Web of Science, Cochrane library, and Wanfang database for published data on the use of BIPSS in Cushing syndrome differential diagnosis as of October 2019. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and receiver operating characteristic (ROC) curves were calculated based on the relevant data. Results This meta-analysis included a total of 23 studies with 1642 patients. The calculated sensitivity, specificity, PLR, and NLR were 0.94 (95% confidence interval, CI: 0.91–0.96), 0.89 (95% CI: 0.79–0.95), 8.8 (95% CI: 4.3–17.9), and 0.07 (95% CI: 0.04–0.11), respectively. The pooled DOR and area under the ROC curve were 129 (95% CI: 48–345) and 0.97 (95% CI: 0.95–0.98), respectively. Conclusion This meta-analysis indicated that BIPSS had high diagnostic value for detecting ACTH in patients with ACTH-dependent Cushing syndrome, and BIPSS should be used as an effective method to identify ACTH-secretion sources.

Precise earthquake locations and InSAR (Interferometric Synthetic Aperture Radar) deformation observation are the major methods to understand the earthquake occurrence and disaster-causing process. This paper proposes a processing framework for analyzing strong earthquake mechanisms from one-dimensional velocity inversion to precise earthquake locations combined with InSAR deformation observation, and discusses earthquake-generating fault and dynamic mechanisms of tectonic deformation. We analyzed the Menyuan Ms 6.9 earthquake in 2022 and discuss the historical seismic activities and corresponding stress adjustment processes in the research region. To analyze and study the seismogenic structure and mechanism of the earthquake, we investigated the spatial and temporal distribution characteristics of the Menyuan earthquake sequence and analyzed the InSAR coseismic deformation field. We obtained the precise locations of the main shock and aftershocks and the coseismic InSAR deformation field of the main shock. It was confirmed that the Ms 6.9 earthquake was a shallow sinistral strike-slip earthquake, which led to the sequential activation of the Tuolaishan and Lenglongling faults. The main seismogenic fault of the mainshock was the northwestern end of the Lenglongling fault, and the earthquake rupture was segmented. It can be inferred that the earthquake was a stress-adjusted event triggered in the Qilian-Haiyuan tectonic belt caused by the northeasterly push of the Qinghai-Tibet Plateau. The risk of moderate to high earthquakes in the region remains high in the future, requiring enhanced seismic observations.

ObjectivePrevious studies have reported sex differences in associations between diabetes mellitus (DM) and the risk of developing coronary heart disease (CHD) and stroke; however, the risk for cardiac death and all-cause mortality in women compared with men has not been reported. Therefore, this quantitative meta-analysis was performed to provide reliable estimates of sex differences in the effect of DM on major cardiovascular outcomes and all-cause mortality, irrespective of DM type.DesignMeta-analysis.Data sourcesThe PubMed, Embase and the Cochrane Library databases were systematically searched in April 2018.Eligibility criteriaInvestigations designed as prospective cohort studies that examined the association between DM and major cardiovascular outcomes and all-cause mortality stratified according to sex were included.Data extraction and synthesisData extraction and quality assessment were independently performed by 2 of the authors, and the relative risk ratio (RRR) obtained using a random effects model was used to measure sex differences in the associations of DM with major cardiovascular outcomes and all-cause mortality.ResultsThirty prospective cohort studies that reported data from 1 148 188 individuals were included. The pooled women-to-men RRR suggested that female sex was associated with an increased risk for CHD (RRR 1.52(95% CI 1.32 to 1.76); p<0.001), stroke (RRR 1.23(95% CI 1.09 to 1.39); p=0.001), cardiac death (RRR 1.49(95% CI 1.11 to 2.00); p=0.009) and all-cause mortality (RRR 1.51(95% CI 1.23 to 1.85); p<0.001). In addition, sex differences for the investigated outcomes in the comparison between DM and non-DM patients were variable after stratification of studies according to publication year, country, sample size, assessment of DM, follow-up duration, adjustment for important cardiovascular risk factors and study quality.ConclusionsFindings of the present study suggested that women with DM had an extremely high risk for CHD, stroke, cardiac death and all-cause mortality compared with men with DM.

This study investigates spatiotemporal b value variations and seismic interaction networks preceding the Mwg 7.1 Dingri earthquake that struck southern Tibet on 7 January 2025. Using relocated earthquake catalogs (2021–2025) and dual-method analysis combining b value mapping with Granger causality network modeling, we reveal systematic precursory patterns. Spatial analysis shows that the most significant b value reduction (Δb > 0.5) occurred north of the mainshock epicenter at seismogenic depths (5–15 km), closely aligning with subsequent aftershock concentration zones. Granger causality analysis reveals a progressive network simplification: from 73 causal links among 28 nodes during the background period (2021–2023) to 49 links among 34 nodes pre-mainshock (2023–2025) and finally to 6 localized links post-rupture. This transition from distributed system-wide interactions to localized “locked-in” dynamics reflects the stress concentration onto the primary asperity approaching critical failure. The convergence of b value anomalies and network evolution provides a comprehensive framework linking quasi-static stress states with dynamic system behavior. These findings offer valuable insights for understanding earthquake nucleation processes and improving seismic hazard assessment in the Tibetan Plateau and similar complex tectonic environments.

KEY MESSAGE : Using map-based cloning of Tril gene, we identified a homeodomain-leucine zipper gene involved in the initiation of multicellular trichomes (including the spines of fruit) in cucumber. Fruit spines are a special type of trichome that impacts the quality and appearance of cucumber (Cucumis sativus L.) fruit. Scanning electron microscopy revealed that the trichome-less (tril) mutant originating from European greenhouse cucumber has a completely glabrous phenotype on cotyledons, hypocotyls, young leaves, fruits, and fruit stalks. Genetic analysis revealed that tril was inherited as a recessive allele at a single locus. Using 1058 F₂ individuals derived from a cross between cucumber tril mutant CGN19839 and the micro-trichome (mict) mutant 06-2, tril was mapped to chromosome 6, and narrowed down to a 37.4 kb genomic region which carries seven predicted genes. Genetic and molecular analyses revealed that gene Cucsa.045360 is a possible candidate gene for the differentiation of epidermal cells to trichomes. It is a member of the class IV homeodomain-leucine zipper (HD-Zip IV) family and encodes homeodomain and START domain, sharing 66.7 % predicted amino acid sequence identity to PROTODERMAL FACTOR2 (PDF2) and 35.0 % to GLABRA2 (GL2) of Arabidopsis. The homeobox domain had changed amino acid sequence because of an insertion in tril mutant. The results of genetic analysis and transcriptome profiling indicated that the Tril gene had an epistatic effect on the Mict gene in trichome development. Phenotypes of the tril mutant such as glabrous fruits and female flowers at every node could be used in developing new cultivars.

Carbapenem-resistant Enterobacteriaceae are some of the most important pathogens responsible for nosocomial infections, which can be challenging to treat. The blaNDM carbapenemase genes, which are expressed by New Delhi metallo-β-lactamase (NDM)-producing Escherichia coli isolates, have been found in humans, environmental samples, and multiple other sources worldwide. Importantly, these genes have also been found in farm animals, which are considered an NDM reservoir and an important source of human infections. However, the dynamic evolution of blaNDM genetic contexts and blaNDM-harboring plasmids has not been directly observed, making it difficult to assess the extent of horizontal dissemination of the blaNDM gene. In this study, we detected NDM-1 (n = 1), NDM-5 (n = 24), and NDM-9 (n = 8) variants expressed by E. coli strains isolated from poultry in China from 2016 to 2017. By analyzing the immediate genetic environment of the blaNDM genes, we found that IS26 was associated with multiple types of blaNDM multidrug resistance regions, and we identified various IS26-derived circular intermediates. Importantly, in E. coli strain GD33, we propose that IncHI2 and IncI1 plasmids can fuse when IS26 is present. Our analysis of the IS26 elements flanking blaNDM allowed us to propose an important role for IS26 elements in the evolution of multidrug-resistant regions (MRRs) and in the dissemination of blaNDM. To the best of our knowledge, this is the first description of the dynamic evolution of blaNDM genetic contexts and blaNDM-harboring plasmids. These findings could help proactively limit the transmission of these NDM-producing isolates from food animals to humans. IMPORTANCE Carbapenem resistance in members of the order Enterobacterales is a growing public health problem that is associated with high mortality in developing and industrialized countries. Moreover, in the field of veterinary medicine, the occurrence of New Delhi metallo-β-lactamase-producing Escherichia coli isolates in animals, especially food-producing animals, has become a growing concern in recent years. The wide dissemination of blaNDM is closely related to mobile genetic elements (MGEs) and plasmids. Although previous analyses have explored the association of many different MGEs with mobilization of blaNDM, little is known about the evolution of various genetic contexts of blaNDM in E. coli. Here, we report the important role of IS26 in forming multiple types of blaNDM multidrug resistance cassettes and the dynamic recombination of plasmids bearing blaNDM. These results suggest that significant attention should be paid to monitoring the transmission and further evolution of blaNDM-harboring plasmids among E. coli strains of food animal origin.

Pathogen/microbe-associated molecular patterns (PAMPs/MAMPs) trigger plant immunity that forms the first line inducible defenses in plants. The regulatory mechanism of MAMP-triggered immunity, however, is poorly understood. Here, we show that Arabidopsis thaliana transcription factors ETHYLENE INSENSITIVE3 (EIN3) and ETHYLENE INSENSITIVE3-LIKE1 (EIL1), previously known to mediate ethylene signaling, also negatively regulate PAMP-triggered immunity. Plants lacking EIN3 and EIL1 display enhanced PAMP defenses and heightened resistance to Pseudomonas syringae bacteria. Conversely, plants overaccumulating EIN3 are compromised in PAMP defenses and exhibit enhanced disease susceptibility to Pseudomonas syringae. Microarray analysis revealed that EIN3 and EIL1 negatively control PAMP response genes. Further analyses indicated that SALICYLIC ACID INDUCTION DEFICIENT2 (SID2), which encodes isochorismate synthase required for pathogen-induced biosynthesis of salicylic acid (SA), is a key target of EIN3 and EIL1. Consistent with this, the ein3-1 eil1-1 double mutant constitutively accumulates SA in the absence of pathogen attack, and a mutation in SID2 restores normal susceptibility in the ein3 eil1 double mutant. EIN3 can specifically bind SID2 promoter sequence in vitro and in vivo. Taken together, our data provide evidence that EIN3/EIL1 directly target SID2 to downregulate PAMP defenses.