Monocyte/Macrophage-Mediated Transport of Dual-Drug ZIF Nanoplatforms Synergized with Programmed Cell Death Protein-1 Inhibitor Against Microsatellite-Stable Colorectal Cancer.

Microsatellite-stable colorectal cancer (MSS-CRC) exhibits resistance to programmed cell death protein-1 (PD-1) therapy. Improving the infiltration and tumor recognition of cytotoxic T-lymphocytes (CTLs) is a promising strategy, but it encounters huge challenges from drug delivery and mechanisms aspects. Here, a zeolitic imidazolate framework (ZIF) coated with apoptotic body membranes derived from MSS-CRC cells is engineered for the co-delivery of ginsenoside Rg1 (Rg1) and atractylenolide-I (Att) to MSS-CRC, named as Ab@Rg1/Att-ZIF. This system is selectively engulfed by Ly-6C+ monocytes during blood circulation and utilizes a "hitchhiking" mechanism to migrate toward the core of MSS-CRC. Ab@Rg1/Att-ZIF undergoes rapid disassembly in the tumor, released Rg1 promotes the processing and transportation of tumor antigens in dendritic cells (DCs), enhancing their maturation. Meanwhile, Att enhances the activity of the 26S proteasome complex in tumor cells, leading to increased expression of major histocompatibility complex class-I (MHC-I). These coordinated actions enhance the infiltration and recognition of CTLs in the center of MSS-CRC, significantly improving the tumor inhibition of PD-1 treatment from ≈5% to ≈69%. This innovative design, involving inflammation-guided precise drug co-delivery and a rational combination, achieves synergistic engineering of the tumor microenvironment, providing a novel strategy for successful PD-1 treatment of MSS-CRC.

Enhancing Thermoelectric Performance of n-Type Bi2Te2.7Se0.3 through Incorporation of Amorphous Si3N4 Nanoparticles.

Bi2Te3-based thermoelectric (TE) materials are the state-of-the-art compounds for commercial applications near room temperature. Nevertheless, the application of the n-type Bi2Te2.7Se0.3 (BTS) is restricted by the comparatively low figure of merit (ZT) and intrinsic embrittlement. Here, we show that through dispersion of amorphous Si3N4 (a-Si3N4) nanoparticles both 14% increase in power factor (at 300 K) and 48% decrease in lattice thermal conductivity are simultaneously realized. The increased power factor comes from enhanced thermopower and reduced electrical resistivity while the reduced lattice thermal conductivity originates mainly from scattering of middle- and low-frequency phonons at the incorporated a-Si3N4 nanoparticles. As a result, a large ZTmax = 1.19 (at 373 K) and an average ZTave ∼ 1.12 (300-473 K) with better mechanical properties are achieved for the BTS/0.25 wt % Si3N4 sample. Present results demonstrate that the incorporation of a-Si3N4 is a promising way to improve TE performance.

Homologous-magnetic dual-targeted metal-organic framework to improve the Anti-hepatocellular carcinoma efficacy of PD-1 inhibitor.

The insufficient abundance and weak activity of tumour-infiltrating lymphocytes (TILs) are two important reasons for the poor efficacy of PD-1 inhibitors in hepatocellular carcinoma (HCC) treatment. The combined administration of tanshinone IIA (TSA) and astragaloside IV (As) can up-regulate the abundance and activity of TILs by normalising tumour blood vessels and reducing the levels of immunosuppressive factors respectively. For enhancing the efficacy of PD-1 antibody, a magnetic metal-organic framework (MOF) with a homologous tumour cell membrane (Hm) coating (Hm@TSA/As-MOF) is established to co-deliver TSA&As into the HCC microenvironment. Hm@TSA/As-MOF is a spherical nanoparticle and has a high total drug-loading capacity of 16.13 wt%. The Hm coating and magnetic responsiveness of Hm@TSA/As-MOF provide a homologous-magnetic dual-targeting, which enable Hm@TSA/As-MOF to counteract the interference posed by ascites tumour cells and enhance the precision of targeting solid tumours. Hm coating also enable Hm@TSA/As-MOF to evade immune clearance by macrophages. The release of TSA&As from Hm@TSA/As-MOF can be accelerated by HCC microenvironment, thereby up-regulating the abundance and activity of TILs to synergistic PD-1 antibody against HCC. This study presents a nanoplatform to improve the efficacy of PD-1 inhibitors in HCC, providing a novel approach for anti-tumour immunotherapy in clinical practice.

Boosting Thermoelectric Performance of PbBi2Te4 via Reduced Carrier Scattering and Intensified Phonon Scattering.

Materials with low intrinsic lattice thermal conductivity are crucial in the pursuit of high-performance thermoelectric (TE) materials. Here, the TE properties of PbBi2Te4-xSex (0 ≤ x ≤ 0.6) samples are systematically investigated for the first time. Doping with Se in PbBi2Te4 can simultaneously reduce carrier concentration and increase carrier mobility. The Seebeck coefficient is significantly increased by doping with Se, based on the density functional theory calculation, it is shown to be due to the increased bandgap and electronic density of states. In addition, the lattice strain is enhanced due to the difference in the size of Se and Te atoms, and the multidimensional defects formed by Se doping, such as vacancies, dislocations, and grain boundaries, enhance the phonon scattering and reduce the lattice thermal conductivity by about 37%. Finally, by using Se doping to reduce carrier concentration and thermal conductivity, a large ZTmax = 0.56 (at 574K) is achieved for PbBi2Te3.5Se0.5, which is around 64% larger than those of the PbBi2Te4 pristine sample. This work not only demonstrates that PbBi2Te4 is a potential medium temperature thermoelectric material, but also provides a reference for enhancing thermoelectric properties through defect and energy band engineering.

High Thermoelectric Performance of n-type BiTeSe-Based Composites Incorporated with Both Inorganic and Organic Nanoinclusions.

N-type Bi2Te2.7Se0.3 (BTS) alloy has relatively low thermoelectric performance as compared to its p-type counterpart, which restricts its widespread applications. Herein, we designed and prepared a novel composite system, which consists of an n-type BTS matrix incorporated with both inorganic and organic nanoinclusions. The results indicate that the thermopower of the composite samples can be enhanced by more than 19% upon incorporating inorganic nanophase AgBi3S5 (ABS) due to the energy-dependent carrier scattering, which ensures a high power factor. On the other hand, further incorporation of organic nanophase polypyrrole (PPy) can drastically reduce its lattice thermal conductivity owing to the strong scattering of mid- and low-frequency phonons at these nanoinclusions. As a result, high figures of merit ZTmax = 1.3 at 348 K and ZTave = 1.17 (300-500 K) are achieved with improved mechanical properties in BTS-based composites incorporated with 1.5 wt % ABS and 0.5 wt % PPy, demonstrating that the incorporation of both inorganic and organic nanoinclusions is an effective way to improve its thermoelectric performance.

Low Thermal Conductivity and High Thermoelectric Performance of Nb-Doped Quarternary Mixed Crystal Nb0.05W0.95-xMox(Se1-xSx)2.

Transition-metal dichalcogenide WSe2 has attracted increasing interest due to its large thermopower (S), low-cost, and environment-friendly constituents. However, its thermoelectric figure of merit, ZT, of WSe2 is limited due to its large lattice thermal conductivity (κL) and low electrical conductivity. In view of WSe2 and MoS2 having the same crystal structure, here we designed and prepared Nb-doped quarternary mixed crystal (MC) Nb0.05W0.95-xMox(Se1-xSx)2 (0 ≤ x ≤ 0.095). The results indicate that the κL of the MC can reach as low as 0.12 W m K-1 at 850 K, being 93% smaller than that of WSe2. Our analysis reveals that its low κL originates chiefly from intense scattering of both high-frequency phonons from point defects (mainly alloying elements) and mid/low-frequency phonons from MoS2 inclusions residual within MC. In addition, the alloying of WSe2 with MoS2 causes a 5-fold increase in cation vacancies (VW‴'), leading to a large increase in hole concentration and electrical conductivity, which gives rise to a ∼7.5 times increase in power factor (reaching 4.2 µ W cm-1 K-2 at 850 K). As a result, a record high ZTmax = 0.63 is achieved at 850 K for the MC sample with x = 0.076, which is 20 times larger than that of WSe2, demonstrating that MC Nb0.05W0.95-xMox(Se1-xSx)2 is a promising thermoelectric material.

Attaining High Figure of Merit in the N-Type Bi2Te2.7Se0.3-Ag2Te Composite System via Comprehensive Regulation of Its Thermoelectric Properties.

n-Type Bi2Te2.7Se0.3 (BTS) is the state-of-the-art thermoelectric material near room temperature. However, the figure of merit ZT of commercial BTS ingots is still limited and further improvement is imperative for their wide applications. Here, the results show that through dispersion of the Ag2Te nanophase in BTS, one can not only elevate its power factor (PF) by as high as 14% (at 300 K) but also reduce its thermal conductivity κtot to as small as ∼29% (at 300 K). Experimental evidences show that the improved PF comes from both increased electron mobility via inhibited Te vacancies and enhanced thermopower due to energy filtering effect, while the reduction of κtot originates from the drop of both electronic thermal conductivity largely owing to the reduced number of vacancy VTe·· and intensified phonon scattering chiefly from the dispersed Ag2Te nanophase. Consequently, the largest ZTmax = 1.31 (at 350 K) and average ZTave = 1.16 (300-500 K) are achieved for the Bi2Te2.7Se0.3-0.3 wt % Ag2Te composite sample, leading to a projected conversion efficiency η = 8.3% (300-500 K). The present results demonstrate that incorporation of nanophase Ag2Te is an effective approach to boosting the thermoelectric performance of BTS.

Simultaneous Enhancement of the Power Factor and Phonon Blocking in Nb-Doped WSe2.

Transition-metal dichalcogenide WSe2 is a potentially good thermoelectric (TE) material due to its high thermopower (S). However, the low electrical conductivity (σ), power factor (PF), and relatively large lattice thermal conductivity (κL) of pristine WSe2 degenerate its TE performance. Here, we show that through proper substitution of Nb for W in WSe2, its PF can be increased by ∼10 times, reaching 5.44 µW cm-1 K-2 (at 850 K); simultaneously, κL lowers from 1.70 to 0.80 W m-1 K-1. Experiments reveal that the increase of PF originates from both increased hole concentration due to the replacement of W4+ by Nb3+ and elevated thermopower (S) caused by the enhanced density of states effective mass, while the reduced κL comes mainly from phonon scattering at point defects NbW. As a result, a record high figure of merit ZTmax ∼0.42 is achieved at 850 K for the doped sample W0.95Nb0.05Se2, which is ∼13 times larger than that of pristine WSe2, demonstrating that Nb doping at the W site is an effective approach to improve the TE performance of WSe2.

Theoretical Study of Intrinsic and Extrinsic Point Defects and Their Effects on Thermoelectric Properties of Cu2SnSe3.

Current understanding of the intrinsic point defects and potential extrinsic dopants in p-type Cu2SnSe3 is limited, which hinders further improvement of its thermoelectric performance. Here, we show that the dominant intrinsic defects in Cu2SnSe3 are CuSn and VCu under different chemical conditions, respectively. The presence of VCu will damage the hole conduction network and reduce hole mobility. Besides, we find that the substitution of Al, Ga, In, Cd, Zn, Fe, and Mn for Sn can inhibit the formation of VCu; introducing CuSn, FeSn, MnSn, and NiCu defects can significantly enhance electronic density of states near the Fermi level due to the contribution of 3d orbitals. Therefore, increasing the Cu content and/or introducing the above beneficial dopants appropriately are expected to cause enhancement of carrier mobility and/or thermopower of Cu2SnSe3. Furthermore, introducing AgCu, AlSn, ZnSn, GeSn, and MnSn defects can induce large mass and strain field fluctuations, lowering lattice thermal conductivity remarkably. Present results not only deepen one's insights into point defects in Cu2SnSe3 but also provide us with a guide to improve its thermoelectric properties.

An intelligent planning method to optimize high-density residential layouts considering the influence of wind environments.

There is a growing conflict between building density and the comfort of the external environment in residential construction, especially in high-density cities in China. To address this conflict, a sensible building layout has to take both aspects into account. However, it is difficult for traditional planning approaches to produce a sensible building layout. This is partly due to the fact that an architect's subjective experiences are unreliable. On the other hand, the wind environment simulations of professional software are often time-consuming so that they are difficult to apply efficiently in practice. This study therefore focuses on the automatic generation of optimized high-density residential building layouts as well as the fast and accurate calculation of the corresponding wind environments. By combining the automatic optimization function of a genetic algorithm and the prediction function of a fully convolutional neural network, an intelligent planning method is proposed for producing optimal high-density residential building layouts in consideration of the local wind environment. To further verify its practicality and significance, a case study was carried out in the Yangtze River Delta region, China, through the automatic generation of a residential building layout, wind environment simulation, and a scheme comparison for optimization.

Resveratrol inhibits proliferation and induces apoptosis via the Hippo/YAP pathway in human colon cancer cells.

High malignancy and mortality in colon cancer require clarifying the underlying mechanisms of colon cancer carcinogenesis and exploring new targets or drugs for the clinical treatment of colon cancer. Resveratrol (Res), a natural compound, shows cytotoxicity against various tumors. However, the specific anti-cancer mechanism of Res remains unclear. In the present study, we aimed to explore the anti-cancer activity of Res against colon cancer cells and the possible mechanism. The results showed that Res could inhibit cell proliferation and induce cell cycle arrest and apoptosis in HCT116 cells. Western blotting and Polymerase chain reaction (PCR) showed that Res increased the phosphorylated YAP (pYAP) levels and decreased YAP total protein level and decreased the mRNA expression of the YAP signaling downstream genes CTGF and CYR61. The effects of Res on pYAP were enhanced by YAP inhibitor verteporfin (VP). VP also enhanced the effects of Res on decreasing viability and inducing apoptosis. Furthermore, the molecular docking analysis indicated Res could bind with YAP-TEAD through van der Waals, pi-alkyl, and pi-pi stacked interactions. Our findings suggested that the anti-cancer activity of Res may be mediated via activating Hippo/YAP signaling and partially disturbing the interaction between YAP and TEAD. All this evidence supports that Res may be an efficacious drug for colon cancer treatment.

Achieving higher thermoelectric performance of n-type PbTe by adjusting the band structure and enhanced phonon scattering.

Due to the very distinct electronic band structure and lower power factor, the exploration of n-type PbTe as thermoelectric materials has historically fallen behind that of p-type PbTe. In this work, n-type Pb0.97Sb0.03Te-based composites incorporated with Cu12Sb4S13 nanoparticles are synthesized and investigated. Sb doping is utilized to modify its carrier concentration in order to obtain n-type PbTe materials with a high power factor. Then, the incorporation of Cu12Sb4S13 nanoparticles can generate semi-coherent nanophase CuTe, and simultaneously optimize the thermal and electrical properties due to remarkable energy filtering effects and interface scattering in the higher temperature range. Eventually, a peak figure of merit ZT ≈ 1.58 was obtained at 773 K for the sample Pb0.97Sb0.03Te + 1.5 wt% Cu12Sb4S13, indicating that the incorporation of Cu12Sb4S13 in Pb0.97Sb0.03Te is an effective approach to improve its thermoelectric performance.

Atomic Level Defect Structure Engineering for Unusually High Average Thermoelectric Figure of Merit in n-Type PbSe Rivalling PbTe.

Realizing high average thermoelectric figure of merit (ZTave ) and power factor (PFave ) has been the utmost task in thermoelectrics. Here the new strategy to independently improve constituent factors in ZT is reported, giving exceptionally high ZTave and PFave in n-type PbSe. The nonstoichiometric, alloyed composition and resulting defect structures in new Pb1+ x Se0.8 Te0.2 (x = 0-0.125) system is key to this achievement. First, incorporating excess Pb unusually increases carrier mobility (µH ) and concentration (nH ) simultaneously in contrast to the general physics rule, thereby raising electrical conductivity (σ). Second, modifying charge scattering mechanism by the authors' synthesis process boosts a magnitude of Seebeck coefficient (S) above theoretical expectations. Detouring the innate inverse proportionality between nH and µH ; and σ and S enables independent control over them and change the typical trend of PF to temperature, giving remarkably high PFave ≈20 µW cm-1 K-2 from 300 to 823 K. The dual incorporation of Te and excess Pb generates unusual antisite Pb at the anionic site and displaced Pb from the ideal position, consequently suppressing lattice thermal conductivity. The best composition exhibits a ZTave of ≈1.2 from 400 to 823 K, one of the highest reported for all n-type PbQ (Q = chalcogens) materials.

Astrocytic p75NTR expression provoked by ischemic stroke exacerbates the blood-brain barrier disruption.

The disruption of the blood-brain barrier (BBB) plays a critical role in the pathology of ischemic stroke. p75 neurotrophin receptor (p75NTR ) contributes to the disruption of the blood-retinal barrier in retinal ischemia. However, whether p75NTR influences the BBB permeability after acute cerebral ischemia remains unknown. The present study investigated the role and underlying mechanism of p75NTR on BBB integrity in an ischemic stroke mouse model, middle cerebral artery occlusion (MCAO). After 24 h of MCAO, astrocytes and endothelial cells in the infarct-affected brain area up-regulated p75NTR . Genetic p75NTR knockdown (p75NTR+/- ) or pharmacological inhibition of p75NTR using LM11A-31, a selective inhibitor of p75NTR , both attenuated brain damage and BBB leakage in MCAO mice. Astrocyte-specific conditional knockdown of p75NTR mediated with an adeno-associated virus significantly ameliorated BBB disruption and brain tissue damage, as well as the neurological functions after stroke. Further molecular biological examinations indicated that astrocytic p75NTR activated NF-κB and HIF-1α signals, which upregulated the expression of MMP-9 and vascular endothelial growth factor (VEGF), subsequently leading to tight junction degradation after ischemia. As a result, increased leukocyte infiltration and microglia activation exacerbated brain injury after stroke. Overall, our results provide novel insight into the role of astrocytic p75NTR in BBB disruption after acute cerebral ischemia. The p75NTR may therefore be a potential therapeutic target for the treatment of ischemic stroke.

Sortilin deletion in the prefrontal cortex and hippocampus ameliorates depressive-like behaviors in mice via regulating ASM/ceramide signaling.

Major depressive disorder (MDD) is a common psychiatric disorder characterized by persistent mood despondency and loss of motivation. Although numerous hypotheses have been proposed, the possible pathogenesis of MDD remains unclear. Several recent studies show that a classic transporter protein, sortilin, is closely associated with depression. In the present study, we investigated the role of sortilin in MDD using a well-established rodent model of depression. Mice were subjected to chronic unpredictable mild stress (CUMS) for 6 weeks. We showed that the expression levels of sortilin were significantly increased in the prefrontal cortex and hippocampus of CUMS mice. The depressive-like behaviors induced by CUMS were alleviated by specific knockdown of sortilin in the prefrontal cortex and hippocampus. We revealed that sortilin facilitated acid sphingomyelinase (ASM)/ceramide signaling, which activated RhoA/ROCK2 signaling, ultimately causing the transformation of dendritic spine dynamics. Specific overexpression of sortilin in the prefrontal cortex and hippocampus induced depressive-like behaviors, which was mitigated by injection of ASM inhibitor SR33557 (4 µg/µL) into the prefrontal cortex and hippocampus. In conclusion, sortilin knockdown in the prefrontal cortex and hippocampus plays an important role in ameliorating depressive-like behavior induced by CUMS, which is mainly evidenced by decreasing the trafficking of ASM from the trans-Golgi network to the lysosome and reducing the ceramide levels. Our results provide a new insight into the pathology of depression, and demonstrate that sortilin may be a potential therapeutic target for MDD.

Nogo receptor impairs the clearance of fibril amyloid-ß by microglia and accelerates Alzheimer's-like disease progression.

Alzheimer's disease (AD) is characterized by the progressive accumulation of ß-amyloid (Aß)-containing amyloid plaques, and microglia play a critical role in mediating Aß clearance. Mounting evidence has confirmed that the ability of microglia in clearing Aß decreased with aging and AD progress, but the underlying mechanisms are unclear. Previously, we have demonstrated that Nogo receptor (NgR), a receptor for three axon growth inhibitors associated with myelin, can decrease adhesion and migration of microglia to fibrils Aß with aging. However, whether NgR expressed on microglia affect microglia phagocytosis of fibrils Aß with aging remains unclear. Here, we found that aged but not young microglia showed increased NgR expression and decreased Aß phagocytosis in APP/PS1 transgenic mice. NgR knockdown APP/PS1 mice showed simultaneous reduced amyloid burden and improved spatial learning and memory, which were associated with increased Aß clearance. Importantly, Nogo-P4, an agonist of NgR, enhanced the protein level of p-Smad2/3, leading to a significant transcriptional inhibition of CD36 gene expression, which in turn decreased the microglial phagocytosis of Aß. Moreover, ROCK accounted for Nogo-P4-induced activation of Smad2/3 signaling. Finally, the decreasing effect of NgR on microglial Aß uptake was confirmed in a mouse model of intra-hippocampal fAß injection. Our findings suggest that NgR may play an important role in the regulation of Aß homeostasis, and has potential as a therapeutic target for AD.

Boosting Thermoelectric Performance of Cu2SnSe3 via Comprehensive Band Structure Regulation and Intensified Phonon Scattering by Multidimensional Defects.

As an eco-friendly thermoelectric material, Cu2SnSe3 has recently drawn much attention. However, its high electrical resistivity ρ and low thermopower S prohibit its thermoelectric performance. Herein, we show that a widened band gap and the increased density of states are achieved via S alloying, resulting in 1.6 times enhancement of S (from 170 to 277 µV/K). Moreover, doping In at the Sn site can cause a 19-fold decrease of ρ and a 2.2 times enhancement of S (at room temperature) due to both multivalence bands' participation in electrical transport and the further enhancement of the density of states effective mass, which allows a sharp increase in the power factor. As a result, PF = 9.3 µW cm-1 K-2 was achieved at ∼800 K for the Cu2Sn0.82In0.18Se2.7S0.3 sample. Besides, as large as 44% reduction of lattice thermal conductivity is obtained via intensified phonon scattering by In-doping-induced formation of multidimensional defects, such as Sn vacancies, dislocations, twin boundaries, and CuInSe2 nanoprecipitates. Consequently, a record high figure of merit of ZT = 1.51 at 858 K is acquired for Cu2Sn0.82In0.18Se2.7S0.3, which is 4.7-fold larger than that of pristine Cu2SnSe3.

Improved Thermoelectric Performance of Cu12Sb4S13 through Gd-Substitution Induced Enhancement of Electronic Density of States and Phonon Scattering.

Cu12Sb4S13 has aroused great interest because of its earth-abundant constituents and intrinsic low thermal conductivity. However, the applications of Cu12Sb4S13 are hindered by its poor thermoelectric performance. Herein, it is shown that Gd substitution not only causes a significant increase in both electrical conductivity σ and thermopower S but also leads to dramatic drop in lattice thermal conductivity κL. Consequently, large ZT reaches 0.94 at 749 K for Cu11.7Gd0.3Sb4S13, which is ∼41% higher than the ZT value of undoped sample. Rietveld refinements of XRD results show that accompanying inhibition of impurity phase Cu3SbS4, the number of Cu vacancies increases substantially with substituted content x (x ≤ 0.3), which leads to reduced κL owing to intensive phonon scattering by the point defects and increased σ arising from the charged defects (VCu'). Crucially, synchrotron radiation photoelectron spectroscopy reveals substantial increment of electronic density of states at Fermi level upon Gd substitution, which is proven, by our first-principle calculations, to originate from contribution of Gd 4f orbit, resulting in enhancement of S. Our study provides us with a new path to enhance thermoelectric performance of Cu12Sb4S13.

Improving the thermoelectric performance of Cu2SnSe3via regulating micro- and electronic structures.

As a p-type thermoelectric material, Cu2SnSe3 (CSS) has recently drawn much attention, with its constituents being abundant and free of toxic elements. However, the low electrical conductivity σ and thermopower S of CSS prohibit its thermoelectric performance. Here, we show that through mechanical milling, a 14 times increase in σ, around a 2-fold rise in S and a 40% reduction in the lattice thermal conductivity κL (at 300 K) can be achieved, amazingly. Microstructural analysis combined with first-principles calculations reveal that the increased σ originates from the generated Sn vacancies , Se dangling bonds and the reconstructed Cu-Sn-terminated acceptor-like surface states; while the enhanced S comes mainly from the enhanced density of states effective mass caused by the Sn vacancies. In addition, the generated Sn vacancies and the in situ formed SnO2 nanoparticles give rise to strong phonon scattering, leading to the reduced κL. As a result, a maximum ZTm = 0.9 at 848 K is obtained for the CSS specimen milled for 2 h, which is ∼3 times larger than that of CSS milled for 0.5 h.

Increased epigenetic diversity and transient epigenetic memory in response to salinity stress in Thlaspi arvense.

Epigenetic diversity could play an important role in adaptive evolution of organisms, especially for plant species occurring in new and stressful environments. Thlaspi arvense (field pennycress), a valuable oilseed crop, is widespread in temperate regions of the northern hemisphere. In this study, we investigated the effect of salinity stress on the epigenetic variation of DNA methylation and epigenetic stress memory in pennycress using methylation-sensitive amplification polymorphism (MSAP) markers. We examined how the status of DNA methylation changes across individuals in response to salinity stress and whether such an effect of maternal stress could be transferred to offspring for one or two generations in nonstressed environments. Our results based on 306 epiloci indicated no consistent change of DNA methylation status in specific epiloci across individuals within the same conditions. In contrast, we found that the epigenetic diversity at population level increased significantly in response to the stimulation of salinity stress; and this "stimulation effect" could be transferred partially in the form of stress memory to at least two generations of offspring in nonstressed environments. In addition, we observed a parallel change in functionally important traits, that is, phenotypic variation was significantly higher in plants grown under salinity stress compared with those of control groups. Taken together, our results provide novel clues for the increased spontaneous epimutation rate in response to stress in plants, of potential adaptive significance.