DL-3-n-Butylphthalide Ameliorates Post-stroke Emotional Disorders by Suppressing Neuroinflammation and PANoptosis.

Post-stroke emotional disorders such as post-stroke anxiety and post-stroke depression are typical symptoms in patients with stroke. They are closely associated with poor prognosis and low quality of life. The State Food and Drug Administration of China has approved DL-3-n-butylphthalide (NBP) as a treatment for ischemic stroke (IS). Clinical research has shown that NBP alleviates anxiety and depressive symptoms in patients with IS. Therefore, this study explored the role and molecular mechanisms of NBP in cases of post-stroke emotional disorders using network pharmacology and experimental validation. The results showed that NBP treatment significantly increased the percentage of time spent in the center of the middle cerebral artery occlusion (MCAO) rats in the open field test and the percentage of sucrose consumption in the sucrose preference test. Network pharmacology results suggest that NBP may regulate neuroinflammation and cell death. Further experiments revealed that NBP inhibited the toll-like receptor 4/nuclear factor kappa B signaling pathway, decreased the level of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, and interleukin-6, and M1-type microglia markers (CD68, inducible nitric oxide synthase), and reduced the expression of PANoptosis-related molecules including caspase-1, caspase-3, caspase-8, gasdermin D, and mixed lineage kinase domain-like protein in the hippocampus of the MACO rats. These findings demonstrate that the mechanisms through which NBP ameliorates post-stroke emotional disorders in rats are associated with inhibiting neuroinflammation and PANoptosis, providing a new strategy and experimental basis for treating post-stroke emotional disorders.

False recall is associated with larger caudate in males but not in females.

After learning semantically related words, some people are more likely than others to incorrectly recall unstudied but semantically related lures (i.e., Deese-Roediger-McDermott [DRM] false recall). Previous studies have suggested that neural activity in subcortical regions (e.g., the caudate) is involved in false memory, and that there may be sex differences in the neural basis of false memory. However, sex-specific associations between subcortical volumes and false memory are not well understood. This study investigated whether sex modulates the associations between subcortical volumes and DRM false recall in 400 healthy college students. Volumes of subcortical regions including the caudate, accumbens, amygdala, hippocampus, pallidum, putamen and thalamus were obtained from structural magnetic resonance images and measured using FreeSurfer. The results showed that males had lower true and false recall but larger subcortical volumes than females. Interestingly, higher false recall was associated with a larger caudate in males, but not in females. This association was significant after controlling for age and intracranial volume. This study provides new evidence on the neural basis of false recall. It suggests that the caudate plays a role in false recall in young men, and that future studies of the neural correlates of false memory should consider sex differences.

Catalysts of Healing: A Symphony of Synthesis and Clinical Artistry in Small-Molecule Agents for Breast Cancer Alleviation.

Breast cancer, characterized by its molecular intricacy, has witnessed a surge in targeted therapeutics owing to the rise of small-molecule drugs. These entities, derived from cutting-edge synthetic routes, often encompassing multistage reactions and chiral synthesis, target a spectrum of oncogenic pathways. Their mechanisms of action range from modulating hormone receptor signaling and inhibiting kinase activity, to impeding DNA damage repair mechanisms. Clinical applications of these drugs have resulted in enhanced patient survival rates, reduction in disease recurrence, and improved overall therapeutic indices. Notably, certain molecules have showcased efficacy in drug-resistant breast cancer phenotypes, highlighting their potential in addressing treatment challenges. The evolution and approval of small-molecule drugs have ushered in a new era for breast cancer therapeutics. Their tailored synthetic pathways and defined mechanisms of action have augmented the precision and efficacy of treatment regimens, paving the way for improved patient outcomes in the face of this pervasive malignancy. The present review embarks on a detailed exploration of small-molecule drugs that have secured regulatory approval for breast cancer treatment, emphasizing their clinical applications, synthetic pathways, and distinct mechanisms of action.

Five Porous Complexes Constructed from a Racemic Ligand: Synthesis, Chiral Self-Assembly, Iodine Adsorption, and Desorption Properties.

Herein, a chiral bispyridyl ligand (L) was designed and synthesized using a Schiff base condensation reaction, followed by a 1,3-H shift. Five complexes, [Zn2L2(OAc)4] (1), {[CdLCl2(DMF)]·4H2O}n (2), [Cd2L2I4]·4H2O (3), {[CdL2(H2O)2](NO3)2·2CH3OH}n (4), and [Hg2L2Cl4]·2DMF (5), were synthesized and characterized upon its reaction with Zn(II), Cd(II), or Hg(II) ions, respectively. X-ray crystallography shows that the organic compound exists as a racemic ligand with equal amounts of its R- and S-isomers, and all of the synthesized complexes exhibit heterochiral self-assembly via a chiral self-discrimination process. Complexes 1, 3, and 5 exist as centrosymmetric binuclear metallamacrocycles, while complexes 2 and 4 exist as 1D looped-chain coordination polymers. Inspired by the assembled structures of the five complexes, I2 adsorption/desorption measurements for the complexes were carried out. The results show that complexes 1 and 5 exhibit good adsorption capacities toward I2 in n-hexane and in water, respectively.

Coordination-Driven Heterochiral Self-Assembly: Construction of Cd(II) Coordination Polymers with Sorption Behaviors for Iodine and Dyes.

A racemic bispyridyl ligand (L) was synthesized via a Schiff base condensation reaction. Four Cd(II) complexes, {[CdL2Cl2]·2DMF}n (1), [CdLI2]n (2), {[CdL2Br2]·4H2O}n (3), and {[CdL2(H2O)2](NO3)2·2CH3OH·8H2O}n (4), were synthesized and further characterized based on this ligand. Single-crystal structures show that the coordination-driven assembly of the bispyridyl ligand with Cd(II) salts bearing different counteranions can lead to multidimensional coordination polymers via a heterochiral self-discrimination process. Complex 1 exists as a one-dimensional (1D) looped chain polymer, and complex 2 exists as a 1D zigzag chain polymer. Complex 3 is a 2D grid coordination polymer, and complex 4 exists as a 3D framework polymer. Furthermore, the iodine sorption capacities of the four complexes were investigated in the solution of n-hexane and water as well as in the iodine steam. The dye sorption behaviors were investigated in water, which showed that complex 2 exhibited good adsorption for crystal violet (CV), while complex 4 had good adsorption capability toward direct yellow 4 (DY).

An efficient numerical method on modified space-time sparse grid for time-fractional diffusion equation with nonsmooth data.

In this paper, we focus on developing a high efficient algorithm for solving d-dimension time-fractional diffusion equation (TFDE). For TFDE, the initial function or source term is usually not smooth, which can lead to the low regularity of exact solution. And such low regularity has a marked impact on the convergence rate of numerical method. In order to improve the convergence rate of the algorithm, we introduce the space-time sparse grid (STSG) method to solve TFDE. In our study, we employ the sine basis and the linear element basis for spatial discretization and temporal discretization, respectively. The sine basis can be divided into several levels, and the linear element basis can lead to the hierarchical basis. Then, the STSG can be constructed through a special tensor product of the spatial multilevel basis and the temporal hierarchical basis. Under certain conditions, the function approximation on standard STSG can achieve the accuracy order O(2-JJ) with O(2JJ) degrees of freedom (DOF) for d=1 and O(2Jd) DOF for d>1, where J denotes the maximal level of sine coefficients. However, if the solution changes very rapidly at the initial moment, the standard STSG method may reduce accuracy or even fail to converge. To overcome this, we integrate the full grid into the STSG, and obtain the modified STSG. Finally, we obtain the fully discrete scheme of STSG method for solving TFDE. The great advantage of the modified STSG method can be shown in the comparative numerical experiment.

Dynamic changes in neural representations underlie the repetition effect on false memory.

Restudying word lists (e.g., dream, awake, and bed) strengthens true memory of the studied words and reduces false memory for unstudied but semantically related lures (e.g., sleep). Yet, the neural mechanisms involved in this repetition effect on false memory remain unclear. Possible mechanisms involve item-specific and semantic neural representations at encoding, and the memory strength between encoding and retrieval. This study first replicated the behavioral results (Exp. 1) and then investigated various neural mechanisms by using slow event-related functional magnetic resonance imaging (fMRI) and representational similarity analysis (Exp. 2). Behavioral results confirmed that restudy improved true memory and reduced false memory. The fMRI results showed that restudy induced item-specific neural representations at encoding in the left occipital pole, but reduced neural overlap between semantic representations at encoding in the left temporal pole. Individual differences in these two encoding neural mechanisms were correlated with the behavioral measure of false memory, with greater restudy-induced representational changes at encoding (item-specific neural representations and reduced neural overlap between semantic representations) being associated with lower false memory. Moreover, restudy enhanced the memory strength between encoding and retrieval in the visuoparietal cortex but reduced it in the frontal cortex. These findings suggest that dynamic changes in neural representations underlie the repetition effect on false memory, supporting a dual-coding neural framework.

Coordination-Driven Self-Assembly of Complexes Constructed from Two Helical Ligands: Synthesis, Structures, and Selective Gas Adsorption Properties.

Two helical ligands (L1 and L2) were designed and synthesized by a Schiff base condensation reaction. Eight complexes, {[Zn(L1)I2]·H2O}n (1), [Cd2(L1)2I4(CH3OH)2] (2), [Hg2(L1)2I4] (3), [Ag(L1)NO3]n (4), [Ag2(L1)2(NO3)2DMSO]·H2O (5), {[Zn2(L2)2Cl4]·2CHCl3}n (6), {[Ag(L2)]·NO3}n (7), and {[Ag(L2)NO3]·CH3OH}n (8), were synthesized and characterized based on these two ligands. The crystal structures show that both Schiff base compounds exist as racemic ligands with equal amounts of P- and M-helicity, and the assembly of these racemic ligands with metal ions can lead to homochiral or heterochiral complexes via a chiral self-recognition or self-discrimination process. Complexes 2, 3, and 5 exist as heterochiral metallomacrocycles with a figure-eight conformation. Complexes 1, 6, and 8 exist as one-dimensional (1D) homochiral helical chain coordination polymers, while complexes 4 and 7 exist as 1D heterochiral helical chain coordination polymers. Furthermore, gas and vapor adsorption measurements show that all of the synthesized complexes exhibit good selective adsorption capacities toward methanol and ethanol vapor over N2, H2, and O2.

TAK1 of blunt snout bream promotes NF-κB activation via interaction with TAB1 in response to pathogenic bacteria.

Transforming growth factor-ß activated kinase-1 (TAK1) is an important upstream signaling molecules involved in the NF-κB signaling pathway. TAK1 interacts with TAB1 to form the TAK1-TAB1 complex, which elicits NF-κB activation through a series of cascade reactions in mammals. However, the function of TAK1 in blunt snout bream (Megalobrama amblycephala ( maTak1) and the effects of their interaction between TAK1 and TAB1 on the NF-κB activation still remains largely unknown. In the present study, maTak1 was cloned and characterized successfully based on transcriptome data. Its open reading frame is composed of 1626 nucleotides and the predicted maTAK1 protein contains 541 amino acids, which includes an N-terminal Serine/Threonine protein kinases (S/TKc) and a C-terminal coiled-coil region. Phylogenetic analysis showed that maTAK1 were clustered with those of other teleosts. MaTak1 displayed ubiquitous transcriptional expression in all the examined tissues of healthy blunt snout bream but with varied expression levels. And maTrak1 expression was dramatically enhanced in different tissues and MAF cells after LPS stimulation and A. hydrophila challenge. The result from subcellular localization analysis indicated that both maTAK1 and maTAB1 were cytoplasmic protein. The activity of NF-κB promoter could not be induced by overexpression of maTak1 or maTab1 alone, however, it could be enhanced by co-expression of maTak1 and maTab1. Co-immunoprecipitation and subcellular co-localization assay revealed that maTAK1 can combine with maTAB1 directly. The transcriptional expression level of pro-inflammatory cytokines (IL-1ß, IL-6 and IL-8) increased distinctly after the overexpression of maTak1 and maTab1. Taken together, the data obtained in this study demonstrated that the direct interaction between maTAK1 and maTAB1 might play a pivotal role in mediating host innate immune response to pathogen invasion by the production of pro-inflammatory cytokines via NF-κB signaling pathway, which might lay a solid foundation for the establishment of novel therapeutic approach to combat bacterial infection in fish.

Multiple interactive memory representations underlie the induction of false memory.

Theoretical and computational models such as transfer-appropriate processing (TAP) and global matching models have emphasized the encoding-retrieval interaction of memory representations in generating false memories, but relevant neural mechanisms are still poorly understood. By manipulating the sensory modalities (visual and auditory) at different processing stages (learning and test) in the Deese-Roediger-McDermott task, we found that the auditory-learning visual-test (AV) group produced more false memories (59%) than the other three groups (42∼44%) [i.e., visual learning visual test (VV), auditory learning auditory test (AA), and visual learning auditory test (VA)]. Functional imaging results showed that the AV group's proneness to false memories was associated with (i) reduced representational match between the tested item and all studied items in the visual cortex, (ii) weakened prefrontal monitoring process due to the reliance on frontal memory signal for both targets and lures, and (iii) enhanced neural similarity for semantically related words in the temporal pole as a result of auditory learning. These results are consistent with the predictions based on the TAP and global matching models and highlight the complex interactions of representations during encoding and retrieval in distributed brain regions that contribute to false memories.

Conspecific odor cues induce different vocal responses in serrate-legged small treefrogs, but only in the absence of acoustic signals.

BACKGROUND: Signal detection is crucial to survival and successful reproduction, and animals often modify behavioral decisions based on information they obtained from the social context. Undeniably, the decision-making in male-male competition and female choice of anurans (frogs and toads) depends heavily on acoustic signals. However, increasing empirical evidence suggests that additional or alternative types of cue (e.g., visual, chemical, and vibratory) can be used to detect, discriminate and locate conspecifics in many anuran species. Nevertheless, few studies have investigated whether conspecific odor cues affect male's calling behavior. In this study, we conducted an experiment to investigate whether and how different chemical cues (male odors, female odors, and stress odors) from conspecifics affect male's calling strategies in serrate-legged small treefrogs (Kurixalus odontotarsus), and whether the combined chemical and acoustic stimuli have additive effects on calling behavior or not. RESULTS: We found that compared with female odors, male K. odontotarsus reduced calling investment in response to male odors or stress odors, in the absence of rival's advertisement calls. When odor stimuli and advertisement calls were presented simultaneously, however, there were no differences in the vocal response of focal males among odor groups. CONCLUSIONS: These results provide evidence that male treefrogs switch calling investment according to different odor cues from conspecifics, and further demonstrate that calling behavior can be affected by chemical cues in anuran species. Our study highlights the potential role of airborne chemical cues in sex identification and contributes to increase our understanding of anuran communication.

Role of the BDNF/TrkB/CREB signaling pathway in the cytotoxicity of bisphenol S in SK-N-SH cells.

Bisphenol S (BPS) is associated with neurotoxicity, but its molecular mechanisms are unclear. Our aim was to investigate the role of the brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB)/cAMP-response element-binding protein (CREB) signaling pathway in BPS-induced cytotoxicity in SK-N-SH cells. The cells were treated with various concentrations of BPS, and cell viability, apoptosis rate, mitochondrial membrane potential (MMP), and the BDNF, cleaved-caspase-3, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), TrkB, CREB, and phospho-CREB (p-CREB) levels were determined. The effects of pretreatment with the TrkB activator 7,8-dihydroxyflavone (7,8-DHF) were also explored. BPS decreased SK-N-SH cell viability and altered their morphology. Their apoptosis rate was increased, as were the levels of the proapoptotic proteins Bax and cleaved-caspase-3, but MMP was decreased. Thus, BPS may induce mitochondria-dependent apoptosis pathways. BPS also reduced the BDNF, TrkB, and p-CREB levels, and pretreatment with 7,8-DHF alleviated its cytotoxic effects. Thus, BPS-induced cytotoxicity might be mediated by the BDNF/TrkB/CREB signaling pathway.

Oxidative stress-mediated apoptosis is involved in bisphenol S-induced reproductive toxicity in male C57BL/6 mice.

The reproductive toxicity of bisphenol S (BPS) in male mammals and its possible mechanism are not clear. We investigated the effects and possible mechanism of action of BPS on adult male C57BL/6 mice. We found that exposure to 200-mg/kg BPS resulted in a significant decrease in the sperm count in the caput/corpus and cauda epididymis, significantly decreased sperm motility, and significantly increased the sperm deformity. Histological evaluation revealed that BPS exposure caused a decrease of spermatozoa in the lumen of seminiferous tubules and a reduction in the proportion of Stage VII or VIII seminiferous tubules in the BPS-treated groups. Furthermore, ultrastructure analysis revealed BPS-induced mitochondrial damage and apoptosis in spermatogenic cells. Moreover, BPS exposure-induced oxidative stress in testicular tissues. Further, dUTP-biotin nick end labeling (TUNEL) assay showed that BPS induced the apoptosis of spermatogenic cells in a dose-dependent manner. BPS also significantly upregulated cleaved caspase-8, cleaved caspase-9, cleaved caspase-3, Fas, and FasL and significantly downregulated the Bcl-2/Bax ratio. These results suggest that BPS-induced oxidative stress in the testis and spermatogenic cell apoptosis potentially impairs spermatogenesis and sperm function, which may be the mechanism of the reproductive toxicity of BPS. The Fas/FasL and mitochondrial signal pathways may be involved in BPS-induced oxidative stress-related apoptosis. These results suggest that BPS-induced oxidative stress in the testis and spermatogenic cell apoptosis potentially impairs spermatogenesis and sperm function, which may be the mechanism of the reproductive toxicity of BPS. The Fas/FasL and mitochondrial signal pathways may be involved in BPS-induced oxidative stress-related apoptosis.

Partitioning heritability analyses unveil the genetic architecture of human brain multidimensional functional connectivity patterns.

Resting-state functional connectivity profiles have been increasingly shown to be important endophenotypes that are tightly linked to human cognitive functions and psychiatric diseases, yet the genetic architecture of this multidimensional trait is barely understood. Using a unique sample of 1,704 unrelated, young and healthy Chinese Han individuals, we revealed a significant heritability of functional connectivity patterns in the whole brain and several subnetworks. We further proposed a partitioned heritability analysis for multidimensional functional connectivity patterns, which revealed the common and unique enrichment patterns of the genetic contributions to brain connectivity patterns for several gene sets linked to brain functions, including the genes expressed preferentially in the central nervous system and those associated with intelligence, educational attainment, attention-deficit/hyperactivity disorder, and schizophrenia. These results for the first time reveal the genetic architecture of multidimensional brain connectivity patterns across different networks and advance our understanding of the complex relationship between gene sets, neural networks, and behaviors.

Male serrate-legged treefrogs adjust competition strategies according to visual or chemical cues from females.

There is increasing evidence that many anurans use multimodal cues to detect, discriminate and/or locate conspecifics and thus modify their behaviors. To date, however, most studies have focused on the roles of multimodal cues in female choice or male-male interactions. In the present study, we conducted an experiment to investigate whether male serrate-legged small treefrogs (Kurixalus odontotarsus) used visual or chemical cues to detect females and thus altered their competition strategies in different calling contexts. Three acoustic stimuli (advertisement calls, aggressive calls and compound calls) were broadcast in a randomized order after a spontaneous period to focal males in one of four treatment groups: combined visual and chemical cues of a female, only chemical cues, only visual cues and a control (with no females). We recorded the vocal responses of the focal males during each 3 min period. Our results demonstrate that males reduce the total number of calls in response to the presence of females, regardless of how they perceived the females. In response to advertisement calls and compound calls, males that perceived females through chemical cues produced relatively fewer advertisement calls but more aggressive calls. In addition, they produced relatively more aggressive calls during the playback of aggressive calls. Taken together, our study suggests that male Kodontotarsus adjust their competition strategies according to the visual or chemical cues of potential mates and highlights the important role of multisensory cues in male frogs' perception of females.

Self-Assembly by Tridentate or Bidentate Ligand: Synthesis and Vapor Adsorption Properties of Cu(II), Zn(II), Hg(II) and Cd(II) Complexes Derived from a Bis(pyridylhydrazone) Compound.

Four complexes, [Cu4L2(OCH3)2(CH3OH)2]·2H2O (1), [Zn2L2Cl4]·2H2O·2CH3OH (2), [Hg2L2Br4]·4CH3OH (3), and {[CdL2Cl2]·4H2O·4CH3OH}n (4), have been synthesized and characterized from a bis(pyridylhydrazone) ligand (L) with copper(II), zinc(II), mercury(II) or cadmium(II), respectively. Complex 1 exists as a centrosymmetric tetranuclear dimer with L as deprotonated tridentate ligand. Complexes 2 and 3 exist as centrosymmetric metallamacrocycles with L as bidentate ligand. Complex 4 exists as a 1D looped-chain coordination polymer. The thermal stabilities and vapor adsorption properties of the four complexes were investigated as well.

A comparison of reproductive isolation between two closely related oak species in zones of recent and ancient secondary contact.

BACKGROUND: Much of the debate over the evolutionary consequences of hybridization on genetic divergence and speciation results from the breakdown or reinforcement of reproductive barriers in secondary hybrid zones. Among hybrid populations established for different lengths of time following secondary contact, stronger reproductive barriers are generally expected to occur in zones with longer contact. However, in plants no detailed investigation of recent and ancient zones of secondary contact has been conducted despite the importance of such a comparative study. Here, we compare pre- and postzygotic reproductive barriers between two closely related oak species, Quercus mongolica and Q. liaotungensis, in such a situation. RESULTS: The recorded flowering times of both species overlapped in both contact zones. The fruit set at 10 and 30 days after interspecific hand pollination was not significantly lower than that after intraspecific pollination whenever Q. mongolica or Q. liaotungensis comprised the maternal parents in both populations. These results indicated that neither prezygotic phenological barriers nor interspecific incompatibility could have resulted in the reproductive isolation between the two species in both hybrid zones. However, the proportion of hybrid seeds produced by both species in the ancient zone was significantly lower than that recorded in the recent zone of secondary contact. In addition, the proportion of hybrid seeds simulated to form, assuming both random mating and an absence of postpollination barriers, was significantly higher than that detected in the ancient contact zone but not in the recent contact zone. These results suggest stronger early-acting postzygotic isolation between the two oak species in the ancient relative to the recent contact zone. CONCLUSIONS: Our comparative study demonstrated that postzygotic barriers during seed maturity were the main contributing factor to total reproductive isolation, particularly in the ancient contact zone, which aided species delimitation. In the recently formed secondary contact zone, pre- and postzygotic barriers were not well developed, and a high frequency of natural hybridization was evident. To our knowledge this study provides the first comparison of reproductive isolation between the ancient and recent secondary contact zones in plants and helps to clarify the evolutionary consequences of hybridization in a temporal context.

Long-term impact of dry eye symptoms on vision-related quality of life after phacoemulsification surgery.

PURPOSE: To observe the long-term changes in dry eye symptoms and vision-related quality of life in age-related cataract patients after phacoemulsification. METHODS: A total of 101 cataract patients after phacoemulsification combined with IOL implantation (Ph-IOL) in one eye were enrolled. Visual acuity, tear film breakup time (BUT), and Schirmer test 1 (ST1) were measured before and 1, 3, and 6 months after surgery. Ocular Surface Disease Index (OSDI) scores were used to evaluate the severity of dry eye symptoms. Utility values were assessed by the time trade-off (TTO), standard gamble for death (SGD), standard gamble for blindness (SGB) and rating scale (RS). RESULTS: The average LogMAR visual acuity in the operated eye was 1.35 ± 0.50 and increased rapidly after Ph-IOL, approaching a peak at 3 months (0.26 ± 0.15). The BUT and ST1 results decreased abruptly 1 month after surgery and gradually recovered until 6 months. OSDI scores increased significantly after surgery and gradually decreased until 6 months. Utility values evaluated by TTO, SGD, SGB and RS before surgery were 0.67 ± 0.19, 0.75 ± 0.15, 0.67 ± 0.20 and 0.2 ± 0.18, respectively, and increased to 0.91 ± 0.06, 0.98 ± 0.04, 0.92 ± 0.52 and 0.91 ± 0.06, 6 months after. Utility values measured with TTO, SGB or RS correlated significantly (P < 0.05) with visual acuity and OSDI scores pre- and postoperatively. CONCLUSIONS: Dry eye symptoms persist more than 3 months after Ph-IOL. Utility values were negatively influenced by dry eye symptoms.

Temperature responses of mutation rate and mutational spectrum in an Escherichia coli strain and the correlation with metabolic rate.

BACKGROUND: Temperature is a major determinant of spontaneous mutation, but the precise mode, and the underlying mechanisms, of the temperature influences remain less clear. Here we used a mutation accumulation approach combined with whole-genome sequencing to investigate the temperature dependence of spontaneous mutation in an Escherichia coli strain. Experiments were performed under aerobic conditions at 25, 28 and 37 °C, three temperatures that were non-stressful for the bacterium but caused significantly different bacterial growth rates. RESULTS: Mutation rate did not differ between 25 and 28 °C, but was higher at 37 °C. Detailed analyses of the molecular spectrum of mutations were performed; and a particularly interesting finding is that higher temperature led to a bias of mutation to coding, relative to noncoding, DNA. Furthermore, the temperature response of mutation rate was extremely similar to that of metabolic rate, consistent with an idea that metabolic rate predicts mutation rate. CONCLUSIONS: Temperature affects mutation rate and the types of mutation supply, both being crucial for the opportunity of natural selection. Our results help understand how temperature drives evolutionary speed of organisms and thus the global patterns of biodiversity. This study also lend support to the metabolic theory of ecology for linking metabolic rate and molecular evolution rate.

DNA methylation biomarkers for the occurrence of lung adenocarcinoma from TCGA data mining.

The development of lung cancer is a combination of multifactor, multistage, and multiple genetic alterations processes. DNA methylation is an important factor. Currently, the study on the genome-scale epigenetic modification for studying the pathogenesis of lung cancer is still lacking. Here, we aimed to identify the epigenetic modifications of lung cancer, thus to provide scientific basis for the personalized medicine, and research of classification screening for lung adenocarcinoma patients. The DNA methylation data, and the corresponding clinical information of lung adenocarcinoma samples were extracted from the Cancer Genome Atlas (TCGA) database. We explored the association of DNA methylation and gene transcription expression of lung adenocarcinoma by identifying the differentially expressed genes, DNA methylated locis, functional gene clusters, and the relevant genes associated with the survival. We identified 17 differentially expressed genes which had differentially methylated locis, 4 functional gene clusters regulated by methylation, and 522 genes, which were relevant to the survival time of patients. Our study suggested that methylation controlled the gene expression in a variety of ways, which had high/low expression and hyper-/hypo-methylation. Genes of different methylation status showed the different survival curve. The genes and methylated locis identified in this study could be potential biomarkers and therapeutic targets for lung adenocarcinoma.