Temperature dependence of thermal conductivity in 1D nonlinear lattices

We examine the temperature dependence of thermal conductivity of one dimensional nonlinear (anharmonic) lattices with and without on-site potential. It is found from computer simulation that the heat conductivity depends on temperature via the strength of nonlinearity. Based on this correlation, we make a conjecture in the effective phonon theory that the mean-free-path of the effective phonon is inversely proportional to the strength of nonlinearity. We demonstrate analytically and numerically that the temperature behavior of the heat conductivity $\kappa\propto1/T$ is not universal for 1D harmonic lattices with a small nonlinear perturbation. The computer simulations of temperature dependence of heat conductivity in general 1D nonlinear lattices are in good agreements with our theoretic predictions. Possible experimental test is discussed.Comment: 6 pages and 2 figures. Accepted for publication in Europhys. Let

Thermal contraction in silicon nanowires at low temperatures

The thermal expansion effect of silicon nanowires (SiNW) in [100], [110] and [111] directions with different sizes is theoretically investigated. At low temperatures, all SiNW studied exhibit thermal contraction effect due to the lowest energy of the bending vibration mode which has negative effect on the coefficient of thermal expansion (CTE). The CTE in [110] direction is distinctly larger than the other two growth directions because of the anisotropy of the bending mode in SiNW. Our study reveals that CTE decreases with an increase of the structure ratio $\gamma=length/diameter$, and is negative in whole temperature range with $\gamma=1.3$.Comment: accepted by Nanoscal

Utilizing Gut Microbiota to Improve Hepatobiliary Tumor Treatments: Recent Advances

Hepatobiliary tumors, which include cholangiocarcinoma, hepatocellular carcinoma (HCC), and gallbladder cancer, are common cancers that have high morbidity and mortality rates and poor survival outcomes. In humans, the microbiota is comprised of symbiotic microbial cells (10-100 trillion) that belong to the bacterial ecosystem mainly residing in the gut. The gut microbiota is a complicated group that can largely be found in the intestine and has a dual role in cancer occurrence and progression. Previous research has focused on the crucial functions of the intestinal microflora as the main pathophysiological mechanism in HCC development. Intestinal bacteria produce a broad range of metabolites that exhibit a variety of pro- and anticarcinogenic effects on HCC. Therefore, probiotic alteration of the gut microflora could promote gut flora balance and help prevent the occurrence of HCC. Recent evidence from clinical and translational studies suggests that fecal microbiota transplant is one of the most successful therapies to correct intestinal bacterial imbalance. We review the literature describing the effects and mechanisms of the microbiome in the gut in the context of HCC, including gut bacterial metabolites, probiotics, antibiotics, and the transplantation of fecal microbiota, and discuss the potential influence of the microbiome environment on cholangiocarcinoma and gallbladder cancer. Our findings are expected to reveal therapeutic targets for the prevention of hepatobiliary tumors, and the development of clinical treatment strategies, by emphasizing the function of the gut microbiota

m6A regulators featured by tumor immune microenvironment landscapes and correlated with immunotherapy in non-small cell lung cancer (NSCLC)

IntroductionRecent research has confirmed the critical role that epigenetic factors play in regulating the immune response. Nonetheless, what role m6A methylation modification might play in the immune response of non-small cell lung cancer (NSCLC) remains vague.MethodsHerein, the gene expression, copy number variations (CNVs), and somatic mutations of 31 m6A regulators in NSCLC and adjacent control samples from the GEO and TCGA databases were comprehensively explored. Using consensus clustering, m6A modification patterns were identified. Correlations between m6A modification patterns and immune cell infiltration traits in the tumor immune microenvironment (TME) were systematically analyzed. Differentially expressed genes were verified and screened by random forest and cox regression analysis by comparing different m6A modification patterns. Based on the retained gene panel, a risk model was built, and m6Ascore for each sample was calculated. The function of m6Ascore in NSCLC prognosis, tumor somatic mutations, and chemotherapy/immunotherapy response prediction were evaluated.ResultsConsensus clustering classified all NSCLC samples into two m6A clusters (m6A_clusterA and m6A_clusterB) according to the expression levels of 25 m6A regulator genes. Hierarchical clustering further divides the NSCLC samples into two m6A gene clusters: m6AgeneclusterA and m6AgeneclusterB. A panel of 83 genes was screened from the 194 differentially expressed genes between m6A gene clusters. Based on this, a risk score model was established. m6A modification clusters, m6A gene clusters, and m6Ascore calculated from the risk model were able to predict tumor stages, immune cell infiltration, clinical prognosis, and tumor somatic mutations. NSCLC patients with high m6Ascore have poor drug resistance to chemotherapy drugs (Cisplatin and Gemcitabine) and exhibit considerable therapeutic benefits and favorable clinical responses to anti-PD1 or anti-CTLA4 immunotherapy.DiscussionIn conclusion, methylation modification patterns mediated by the m6A regulators in individuals play a non-negligible role in prognosis prediction and immunotherapy response, which will facilitate personalized treatment and immunotherapeutic strategies for NSCLC patients in the future

Interaction of two MADS-box genes leads to growth phenotype divergence of all-flesh type of tomatoes

[EN] All-flesh tomato cultivars are devoid of locular gel and exhibit enhanced firmness and improved postharvest storage. Here, we show that SlMBP3 is a master regulator of locular tissue in tomato fruit and that a deletion at the gene locus underpins the All-flesh trait. Intriguingly, All-flesh varieties lack the deleterious phenotypes reported previously for SlMBP3 under-expressing lines and which preclude any potential commercial use. We resolve the causal factor for this phenotypic divergence through the discovery of a natural mutation at the SlAGL11 locus, a close homolog of SlMBP3. Misexpressing SlMBP3 impairs locular gel formation through massive transcriptomic reprogramming at initial phases of fruit development. SlMBP3 influences locule gel formation by controlling cell cycle and cell expansion genes, indicating that important components of fruit softening are determined at early pre-ripening stages. Our findings define potential breeding targets for improved texture in tomato and possibly other fleshy fruits. The all-flesh type of tomato fruits is caused by mutation of the MBP3 gene, however, knocking down MBP3 in certain genotypes also affect plant and fruit development. Here, the authors show that a natural mutation of AGL11, a close homolog of MBP3, is responsible for the phenotypic divergence.The authors are grateful to L. Lemonnier and D. Saint-Martin for transformation and cultivation of tomato plants and GeT-PlaGe core facility (INRAe Toulouse) for ChIP deep sequencing. The authors also want to thank Dr. Christian Chevalier (INRAE et Univsersite de Bordeaux) for helping in analyzing genes related to cell cycle, cell division, and endoreduplication in tomato. This research was supported by the EU H2020 TomGEM 679796 and HARNESSTOM 101000716 projects.Huang, B.; Hu, G.; Wang, K.; Frasse, P.; Maza, E.; Djari, A.; Deng, W.... (2021). Interaction of two MADS-box genes leads to growth phenotype divergence of all-flesh type of tomatoes. Nature Communications. 12(1):1-14. https://doi.org/10.1038/s41467-021-27117-711412

Overexpression of the class D MADS-box gene Sl-AGL11 impacts fleshy tissue differentiation and structure in tomato fruits

MADS-box transcription factors are key elements of the genetic networks controlling flower and fruit development. Among these, the class D clade gathers AGAMOUS-like genes which are involved in seed, ovule, and funiculus development. The tomato genome comprises two class D genes, Sl-AGL11 and Sl-MBP3 , both displaying high expression levels in seeds and in central tissues of young fruits. The potential effects of Sl-AGL11 on fruit development were addressed through RNAi silencing and ectopic expression strategies. Sl-AGL11-down-regulated tomato lines failed to show obvious phenotypes except a slight reduction in seed size. In contrast, Sl-AGL11 overexpression triggered dramatic modifications of flower and fruit structure that include: the conversion of sepals into fleshy organs undergoing ethylene-dependent ripening, a placenta hypertrophy to the detriment of locular space, starch and sugar accumulation, and an extreme softening that occurs well before the onset of ripening. RNA-Seq transcriptomic profiling high-lighted substantial metabolic reprogramming occurring in sepals and fruits, with major impacts on cell wall-related genes. While several Sl-AGL11-related phenotypes are reminiscent of class C MADS-box genes (TAG1 and TAGL1), the modifications observed on the placenta and cell wall and the Sl-AGL11 expression pattern suggest an action of this class D MADS-box factor on early fleshy fruit development

Prognostic analysis of patients with breast cancer based on tumor mutational burden and DNA damage repair genes

BackgroundBreast cancer has a high tumor-specific death rate and poor prognosis. In this study, we aimed to provide a basis for the prognostic risk in patients with breast cancer using significant gene sets selected by analyzing tumor mutational burden (TMB) and DNA damage repair (DDR).MethodsBreast cancer genomic and transcriptomic data were obtained from The Cancer Genome Atlas (TCGA). Breast cancer samples were dichotomized into high- and low-TMB groups according to TMB values. Differentially expressed DDR genes between high- and low-TMB groups were incorporated into univariate and multivariate cox regression model to build prognosis model. Performance of the prognosis model was validated in an independently new GEO dataset and evaluated by time-dependent ROC curves.ResultsBetween high- and low-TMB groups, there were 6,424 differentially expressed genes, including 67 DDR genes. Ten genes associated with prognosis were selected by univariate cox regression analysis, among which seven genes constituted a panel to predict breast cancer prognosis. The seven-gene prognostic model, as well as the gene copy numbers are closely associated with tumor-infiltrating immune cells.ConclusionWe established a seven-gene prognostic model comprising MDC1, PARP3, PSMB1, PSMB9, PSMD2, PSMD7, and PSMD14 genes, which provides a basis for further exploration of a population-based prediction of prognosis and immunotherapy response in patients with breast cancer

Investigating the function of class D MADS-box genes in tomato fruit development

Les facteurs de transcription de type MADS-box représentent des acteurs de premier plan des réseaux de régulation du développement des fleurs et des fruits. Parmi ces régulateurs, la classe D est formée par des régulateurs apparentés aux protéines AGAMOUS qui ont été décrites pour leur implication dans le développement de l'ovule, de la graine et du funicule. On recense deux gènes MADS-box de classe D dans le génome de la tomate: Sl-AGL11 et Sl-MBP3. Des études d'expression par qPCR ont montré que les deux gènes étaient exprimés lors du développement précoce du fruit, mais dans des territoires distincts. Sl-MBP3 est plutôt exprimé dans le placenta et le gel loculaire tandis que Sl-AGL11 est davantage exprimé dans la graine. Ces profils d'expression distinctifs ont été confirmés et affinés grâce à des lignées de tomates exprimant le gène GUS sous le contrôle des promoteurs Sl-MBP3 et Sl-AGL11. Ainsi dans les lignées pSl-MBP3 ::GUS le signal GUS se concentre dans le gel loculaire tandis que les lignées pSl-AGL11 ::GUS le signal est restreint à l'embryon et l'albumen de la graine . Le rôle fonctionnel des gènes Sl-AGL11 et Sl-MBP3 a été alors exploré grâce à différentes lignées de tomate sur-exprimant ou sous-exprimant les deux gènes MADS-box. La surexpression de Sl-AGL11 engendre des modifications spectaculaires de la structure des fleurs et des fruits, notamment la conversion des sépales en organes charnus capables de mûrir sous le contrôle de l'éthylène. Ces lignées présentent aussi une hypertrophie du placenta au détriment de l'espace loculaire, un ramollissement extrême des tissus qui survient prématurément bien avant le mûrissement. De plus, la teneur en amidon et en sucre des sépales et fruits est considérablement accrue. Une analyse transcriptomique par RNA-seq des sépales et des fruits sur-exprimant Sl-AGL11 a mis en évidence l'ampleur de la reprogrammation métabolique induite par l'expression ectopique de Sl-AGL11, laquelle affecte principalement les gènes de la photosynthèse et les gènes de la paroi. La surexpression de Sl-MBP3 aboutit à des phénotypes similaires à ceux observés avec Sl-AGL11, mais de manière plus modérée. La sous-expression de Sl-AGL11 par une approche RNA interférence n'a pas permis de mettre en évidence de phénotypes clairs, à l'exception d'une légère réduction de la taille des graines. A contrario, la répression ciblée de Sl-MBP3 engendre un défaut de différentiation du gel loculaire résultant en une absence de 'jus' accompagnée d'une augmentation de la fermeté des fruits. La répression simultanée de Sl-AGL11 et Sl-MBP3 aboutit elle aussi à l'absence de gel loculaire et à des fruits plus fermes, mais engendre aussi des phénotypes additionnels tel que la réduction de la taille des fruits et des graines ainsi qu'une altération de leur capacité germinative. L'ensemble de ces résultats suggère qu'en plus de leur implication dans la mise en place de la graine, les deux facteurs MADS de classe D de tomate régulent le développement précoce du fruit. En particulier, le gène Sl-MBP3 semble avoir acquis au cours de l'évolution un rôle additionnel en devenant un régulateur majeur de la différentiation du tissu loculaire.MADS-box genes encode transcription factors that are key elements of the genetic networks controlling flower and fruit development. Among these, the class D clade gathers AGAMOUS-like genes involved in seed, ovule and funiculus development. Tomato genome contains two class D genes: Sl-AGL11 and Sl-MBP3. Transcript accumulation analysed by qPCR indicated that Sl-AGL11 and Sl-MBP3 are both expressed at early fruit development but with distinct territories: Sl-MBP3 being highly expressed in the placenta and the locular gel while Sl-AGL11 expression peaked in the seeds. This expression patterning was confirmed in tomato plants expressing promoter-Sl-MBP3-GUS fusion which displayed high GUS signal in the locular gel while in promoter-Sl-AGL11-GUS lines the signals was restricted to seed embryo and endosperm. The functional significance of Sl-AGL11 and Sl-MBP3 was then addressed through RNAi-silencing and ectopic expression strategies. Overexpression of Sl-AGL11 induced the conversion of sepals into carpelloid fleshy organs that undergo ripening, which is reminiscent of the phenotypes observed for class C TAG1 and TAGL1 MADS-box genes. In addition, Sl-AGL11-overexpressing fruits exhibited a marked hypertrophy of the placenta, a reduction of the locular space, and an extreme softening that occurs well before ripening. Moreover, starch and soluble sugar contents were substantially higher in these fruits and fruit-like sepals, corroborating their conversion into a fleshy organ with similar metabolic reorientations. RNA-Seq analyses performed on young fruits and sepals confirmed the metabolic reprogramming induced by the ectopic expression of Sl-AGL11 among which cell wall-related and photosynthetic genes seem to be the most strongly impacted. Over-expression of Sl-MBP3 in tomato resulted in phenotypes similar to those observed with Sl-AGL11 ectopic expression suggesting functional redundancy of the two class D tomato genes. While the RNAi-mediated specific downregulation of Sl-AGL11 did not show any obvious phenotype, Sl-MBP3 specific downregulation resulted in fruits lacking locular gel formation. Conversely, Sl-MBP3-silenced fruits showed an increased firmness. At last, the simultaneous down-regulation of Sl-AGL11 and Sl-MBP3 expression also triggered the loss of gel formation and increased firmness; but it resulted in marked reduction in fruit size and a decrease in seed number, size and germination capacity. Altogether, these results suggest that, in addition to the well-established role in seed development of class D MADS-box genes, Sl-AGL11 and/or Sl-MBP3 strongly affect fleshy fruit development and quality traits, notably by impacting the differentiation of the locular gel

Caractérisation fonctionnelle des gènes MADS de classe D dans le développement du fruit de tomate

Les facteurs de transcription de type MADS-box représentent des acteurs de premier plan des réseaux de régulation du développement des fleurs et des fruits. Parmi ces régulateurs, la classe D est formée par des régulateurs apparentés aux protéines AGAMOUS qui ont été décrites pour leur implication dans le développement de l'ovule, de la graine et du funicule. On recense deux gènes MADS-box de classe D dans le génome de la tomate: Sl-AGL11 et Sl-MBP3. Des études d'expression par qPCR ont montré que les deux gènes étaient exprimés lors du développement précoce du fruit, mais dans des territoires distincts. Sl-MBP3 est plutôt exprimé dans le placenta et le gel loculaire tandis que Sl-AGL11 est davantage exprimé dans la graine. Ces profils d'expression distinctifs ont été confirmés et affinés grâce à des lignées de tomates exprimant le gène GUS sous le contrôle des promoteurs Sl-MBP3 et Sl-AGL11. Ainsi dans les lignées pSl-MBP3 ::GUS le signal GUS se concentre dans le gel loculaire tandis que les lignées pSl-AGL11 ::GUS le signal est restreint à l'embryon et l'albumen de la graine . Le rôle fonctionnel des gènes Sl-AGL11 et Sl-MBP3 a été alors exploré grâce à différentes lignées de tomate sur-exprimant ou sous-exprimant les deux gènes MADS-box. La surexpression de Sl-AGL11 engendre des modifications spectaculaires de la structure des fleurs et des fruits, notamment la conversion des sépales en organes charnus capables de mûrir sous le contrôle de l'éthylène. Ces lignées présentent aussi une hypertrophie du placenta au détriment de l'espace loculaire, un ramollissement extrême des tissus qui survient prématurément bien avant le mûrissement. De plus, la teneur en amidon et en sucre des sépales et fruits est considérablement accrue. Une analyse transcriptomique par RNA-seq des sépales et des fruits sur-exprimant Sl-AGL11 a mis en évidence l'ampleur de la reprogrammation métabolique induite par l'expression ectopique de Sl-AGL11, laquelle affecte principalement les gènes de la photosynthèse et les gènes de la paroi. La surexpression de Sl-MBP3 aboutit à des phénotypes similaires à ceux observés avec Sl-AGL11, mais de manière plus modérée. La sous-expression de Sl-AGL11 par une approche RNA interférence n'a pas permis de mettre en évidence de phénotypes clairs, à l'exception d'une légère réduction de la taille des graines. A contrario, la répression ciblée de Sl-MBP3 engendre un défaut de différentiation du gel loculaire résultant en une absence de 'jus' accompagnée d'une augmentation de la fermeté des fruits. La répression simultanée de Sl-AGL11 et Sl-MBP3 aboutit elle aussi à l'absence de gel loculaire et à des fruits plus fermes, mais engendre aussi des phénotypes additionnels tel que la réduction de la taille des fruits et des graines ainsi qu'une altération de leur capacité germinative. L'ensemble de ces résultats suggère qu'en plus de leur implication dans la mise en place de la graine, les deux facteurs MADS de classe D de tomate régulent le développement précoce du fruit. En particulier, le gène Sl-MBP3 semble avoir acquis au cours de l'évolution un rôle additionnel en devenant un régulateur majeur de la différentiation du tissu loculaire.MADS-box genes encode transcription factors that are key elements of the genetic networks controlling flower and fruit development. Among these, the class D clade gathers AGAMOUS-like genes involved in seed, ovule and funiculus development. Tomato genome contains two class D genes: Sl-AGL11 and Sl-MBP3. Transcript accumulation analysed by qPCR indicated that Sl-AGL11 and Sl-MBP3 are both expressed at early fruit development but with distinct territories: Sl-MBP3 being highly expressed in the placenta and the locular gel while Sl-AGL11 expression peaked in the seeds. This expression patterning was confirmed in tomato plants expressing promoter-Sl-MBP3-GUS fusion which displayed high GUS signal in the locular gel while in promoter-Sl-AGL11-GUS lines the signals was restricted to seed embryo and endosperm. The functional significance of Sl-AGL11 and Sl-MBP3 was then addressed through RNAi-silencing and ectopic expression strategies. Overexpression of Sl-AGL11 induced the conversion of sepals into carpelloid fleshy organs that undergo ripening, which is reminiscent of the phenotypes observed for class C TAG1 and TAGL1 MADS-box genes. In addition, Sl-AGL11-overexpressing fruits exhibited a marked hypertrophy of the placenta, a reduction of the locular space, and an extreme softening that occurs well before ripening. Moreover, starch and soluble sugar contents were substantially higher in these fruits and fruit-like sepals, corroborating their conversion into a fleshy organ with similar metabolic reorientations. RNA-Seq analyses performed on young fruits and sepals confirmed the metabolic reprogramming induced by the ectopic expression of Sl-AGL11 among which cell wall-related and photosynthetic genes seem to be the most strongly impacted. Over-expression of Sl-MBP3 in tomato resulted in phenotypes similar to those observed with Sl-AGL11 ectopic expression suggesting functional redundancy of the two class D tomato genes. While the RNAi-mediated specific downregulation of Sl-AGL11 did not show any obvious phenotype, Sl-MBP3 specific downregulation resulted in fruits lacking locular gel formation. Conversely, Sl-MBP3-silenced fruits showed an increased firmness. At last, the simultaneous down-regulation of Sl-AGL11 and Sl-MBP3 expression also triggered the loss of gel formation and increased firmness; but it resulted in marked reduction in fruit size and a decrease in seed number, size and germination capacity. Altogether, these results suggest that, in addition to the well-established role in seed development of class D MADS-box genes, Sl-AGL11 and/or Sl-MBP3 strongly affect fleshy fruit development and quality traits, notably by impacting the differentiation of the locular gel

Two dimensional automatic active shape model of degenerative disc repaired by low-intensity laser

Objective: Intervertebral disc degeneration is the main factor causing low back pain, and the related long-term treatment can improve the situation of degeneration. This study aimed to investigate the effect of low-intensity laser irradiation on the repair of degenerative intervertebral disc by two dimensional automatic active shape model (2D-AASM). Methods: Nine Bama miniature pigs were randomly divided into three groups: control group (Con), model group (Mod) and laser treatment group (Las). After one month, the discs were treated with low-energy laser for another month. MRI was performed for one month, and the statistical shape model and 2D-AASM of intervertebral disc were established based on the minimum description length method. Results: The model established by the proposed method is more accurate and the segmentation result is more accurate. From the segmented T2-weighted image, the signal intensity of the Mod group decreased significantly, and the signal intensity in the Las group was moderate and high compared with the Mod group. The HE staining display the structure of Con group was damaged, and the construction of Las group was restored compared with Mod group. Conclusions: The 2D-AASM method effectively improves the accuracy of intervertebral disc segmentation. The low-intensity laser has a protective effect on the repair of the degenerative intervertebral disc