Cell–material interactions constitute a key fundamental topic in biomaterials study. Various cell cues and matrix cues as well as soluble factors regulate cell behaviors on materials. These factors ...are coupled with each other as usual, and thus it is very difficult to unambiguously elucidate the role of each regulator. The recently developed material techniques of surface patterning afford unique ways to reveal the underlying science. This paper reviews the pertinent material techniques to fabricate patterns of microscale and nanoscale resolutions, and corresponding cell studies. Some issues are emphasized, such as cell localization on patterned surfaces of chemical contrast, and effects of cell shape, cell size, cell–cell contact, and seeding density on differentiation of stem cells. Material cues to regulate cell adhesion, cell differentiation and other cell events are further summed up. Effects of some physical properties, such as surface topography and matrix stiffness, on cell behaviors are also discussed; nanoscaled features of substrate surfaces to regulate cell fate are summarized as well. The pertinent work sheds new insight into the cell–material interactions, and is stimulating for biomaterial design in regenerative medicine, tissue engineering, and high‐throughput detection, diagnosis, and drug screening.
Various cellular and extracellular matrix's cues are decoupled via surface patterning to elucidate the role of each factor, such as the effect of cell shape on differentiation of stem cells. The pertinent patterning techniques are introduced. Chemical contrast, surface topography, matrix stiffness, and nanoscaled features of substrate surfaces to regulate cell fate are summarized. The cell geometry cues on cell adhesion and differentiation are highlighted.
Cell migration on material surfaces is a fundament issue in the fields of biomaterials, cell biology, tissue engineering, regenerative medicine, etc. Herein, we aim to guide cell migration by flat ...microstripes with significant contrast of cell adhesion and varied geometric features of the adhesive stripes. To this end, we designed and fabricated cell-adhesive arginine-glycine-aspartate (RGD) microstripes on the nonfouling poly(ethylene glycol) (PEG) background and examined the microstripe-guided adhesion and migration of a few cell types. The migration of cell clusters adhering on the RGD regions was found to be significantly affected by the widths and arc radiuses of the guided microstripes. The cells migrated fastest on the straight microstripes with width of about 20 μm, which we defined as single file confined migration (SFCM). We also checked the possible left–right asymmetric bias of cell migration guided by combinatory microstripes with alternative wavy and quasi-straight stripes under a given width, and found that the velocity of CCW (counter clockwise) migration was higher than that of CW (clockwise) migration for primary rat mesenchymal stem cells (rMSCs), whereas no left–right asymmetric bias was observed for NIH3T3 (mouse embryonic fibroblast cell line) and Hela (human cervix epithelial carcinoma cell line) cells. Comparison of migration of cells on the nanotopological stripe and smooth surfaces further confirmed the importance of cell orientation coherence for guided cell migration and strengthened the superiority of SFCM.
The lateral parabrachial nucleus (LPBN) is known to relay noxious information to the amygdala for processing affective responses. However, it is unclear whether the LPBN actively processes ...neuropathic pain characterized by persistent hyperalgesia with aversive emotional responses. Here we report that neuropathic pain-like hypersensitivity induced by common peroneal nerve (CPN) ligation increases nociceptive stimulation-induced responses in glutamatergic LPBN neurons. Optogenetic activation of GABAergic LPBN neurons does not affect basal nociception, but alleviates neuropathic pain-like behavior. Optogenetic activation of glutamatergic or inhibition of GABAergic LPBN neurons induces neuropathic pain-like behavior in naïve mice. Inhibition of glutamatergic LPBN neurons alleviates both basal nociception and neuropathic pain-like hypersensitivity. Repetitive pharmacogenetic activation of glutamatergic or GABAergic LPBN neurons respectively mimics or prevents the development of CPN ligation-induced neuropathic pain-like hypersensitivity. These findings indicate that a delicate balance between excitatory and inhibitory LPBN neuronal activity governs the development and maintenance of neuropathic pain.
Invasive plants are often attacked by both introduced specialist and native generalist natural enemies in new ranges. Soil fertility can potentially alter the interactions of these natural enemies ...with native versus invasive plants in ways that have largely unexplored implications for biological invasions and biological control.
A common garden experiment was conducted to compare the performance of an introduced specialist flea beetle, Agasicles hygrophila, and/or a native generalist nematode, Meloidogyne incognita, on invasive alligator weed, Alternanthera philoxeroides, and its native congener sessile joyweed, Alternanthera sessilis, under different levels of soil nitrogen (N) and phosphorus (P).
At a relatively low or moderate N and P levels, the flea beetle and the nematodes were not significantly affected by each other. Under these conditions, alligator weed responded plastically by producing more branches and biomass, as well as longer stolons, in response to attack by the flea beetle and/or the nematode, compared to sessile joyweed responses to similar levels of damage. However, under a relatively high N and P levels, nematode infestations significantly reduced flea beetle damage on alligator weed, resulting in significantly greater above‐ and below‐ground biomass and longer stolons than plants without herbivory. In contrast, beetle herbivory significantly increased the level of nematode infestations on sessile joyweed, resulting in significantly fewer fine and coarse roots, and lower above‐ and below‐ground biomass compared to plants without herbivory.
Synthesis and applications. Our findings illustrate the importance of soil fertility in mediating interactions between specialist biocontrol agents and native generalists on native versus invasive plants. High phenotypic plasticity seems to be an important attribute that contributes to the success of invasive plants like alligator weed in relatively nutrient‐poor environments. However, nutrient‐rich environments could potentially confer greater growth benefits on invasive plants than on native ones by changing herbivore–herbivore interactions on plants differently. There is a great need to fully investigate the direct and indirect interactions between biocontrol agents and generalists across food webs following classical biocontrol releases. Nutrient measurements of both soil and water bodies should also be incorporated into all stages of biocontrol programmes.
摘要
在新生境中,入侵植物常常会遭受引入的专食性生防天敌与本地广食性天敌的共同胁迫。土壤肥力可能潜在介导这些天敌在入侵植物与本地植物上的表现与相互作用,但这种介导作用对生物入侵和生物防治的影响机制仍缺乏深入研究。
本文通过同质园试验比较了在不同土壤氮、磷有效性水平下,专食性莲草直胸跳甲与本地广布种南方根结线虫对入侵杂草空心莲子草及其本土同属种莲子草的危害差异。
在相对较低或中等的氮磷水平下,莲草直胸跳甲与根结线虫的相互影响作用并不显著。在莲草直胸跳甲和/或根结线虫的危害下,与莲子草相比,空心莲子草的分枝数、生物量和匍匐茎长度均显著增高。而在相对较高的氮磷水平下,与无取食危害相比,根结线虫显著降低了莲草直胸跳甲对空心莲子草的危害,使得空心莲子草的地上地下生物量和匍匐茎长度均显著增高。与之相反,与无植食性生物危害相比,莲草直胸跳甲取食促进了根结线虫对莲子草的危害,莲子草的细根数、粗根数和地上地下生物量均显著降低。
整合与应用:我们的研究结果表明土壤肥力在调节入侵植物和本土植物介导的专食性生防天敌与本地广食性天敌间互作中的重要性。高表型可塑性可能是入侵植物如空心莲子草在相对营养贫乏的环境中成功入侵的重要因素,然而营养丰富的环境可能通过改变植食性动物间的互作使入侵植物潜在获益。因此,在生防天敌释放以后,有必要深入探究生防天敌与本地广食性天敌在整个食物网中的直接和间接相互作用。其次,对土壤和水体的养分测量应贯穿生物防治项目的各个阶段。
Our findings illustrate the importance of soil fertility in mediating interactions between specialist biocontrol agents and native generalists on native versus invasive plants. High phenotypic plasticity seems to be an important attribute that contributes to the success of invasive plants like alligator weed in relatively nutrient‐poor environments. However, nutrient‐rich environments could potentially confer greater growth benefits on invasive plants than on native ones by changing herbivore–herbivore interactions on plants differently. There is a great need to fully investigate the direct and indirect interactions between biocontrol agents and generalists across food webs following classical biocontrol releases. Nutrient measurements of both soil and water bodies should also be incorporated into all stages of biocontrol programmes.
Microglia, CNS resident innate immune cells, respond strongly to activation of TLR3 and TLR4, which recognize viral dsRNA poly(I:C) and bacterial endotoxin LPS, respectively. However, few studies ...have thoroughly and parallelly compared functional phenotypes and downstream mechanisms between LPS- and poly(I:C)-exposed primary microglia. Here, we investigated the responses of mouse primary microglia upon LPS and poly(I:C) stimulation by detecting various phenotypes ranging from morphology, proliferation, secretion, chemotaxis, to phagocytosis. Furthermore, we explored their sequential gene expression and the downstream signal cascades. Interestingly, we found that the microglial activation pattern induced by LPS was distinguished from that induced by poly(I:C). Regarding microglial morphology, LPS caused an ameboid-like shape while poly(I:C) induced a bushy shape. Microglial proliferation was also facilitated by LPS but not by poly(I:C). In addition, LPS and poly(I:C) modulated microglial chemotaxis and phagocytosis differently. Furthermore, genome-wide analysis provided gene-level support to these functional differences, which may be associated with NF-κb and type I interferon pathways. Last, LPS- and poly(I:C)-activated microglia mediated neurotoxicity in a co-culture system. This study extends our understanding of TLR roles in microglia and provides insights into selecting proper inflammatory microglial models, which may facilitate identification of new targets for therapeutic application.
Ceramic oxide electrolytes are outstanding due to their excellent thermostability, wide electrochemical stable windows, superior Li‐ion conductivity, and high elastic modulus compared to other ...electrolytes. To achieve high energy density, all‐solid‐state batteries require thin solid‐state electrolytes that are dozens of micrometers thick due to the high density of ceramic electrolytes. Perovskite‐type Li0.34La0.56TiO3 (LLTO) freestanding ceramic electrolyte film with a thickness of 25 µm is prepared by tape‐casting. Compared to a thick electrolyte (>200 µm) obtained by cold‐pressing, the total Li ionic conductivity of this LLTO film improves from 9.6 × 10−6 to 2.0 × 10−5 S cm−1. In addition, the LLTO film with a thickness of 25 µm exhibits a flexural strength of 264 MPa. An all‐solid‐state Li‐metal battery assembled with a 41 µm thick LLTO exhibits an initial discharge capacity of 145 mAh g−1 and a high capacity retention ratio of 86.2% after 50 cycles. Reducing the thickness of oxide ceramic electrolytes is crucial to reduce the resistance of electrolytes and improve the energy density of Li‐metal batteries.
The energy density of all‐solid‐state lithium‐metal batteries based on oxide electrolytes is dependent on the thickness of the electrolytes. The production and application of freestanding Li0.34La0.56TiO3 ceramic film with a thickness below 41 µm prepared by tape‐casting demonstrate the feasibility and challenges of the commercial application of ceramic oxide electrolytes.
Based on the conservation of resources perspective of person-environment (P-E) fit, the present research integrates P-E fit theory with the socialization literature to examine lagged reciprocal ...relationships between student-university fit and proactive socialization behaviors (i.e., feedback seeking, relationship building with instructors, general socializing, and positive framing). A six-month longitudinal study of 428 freshmen in a Chinese university revealed that relationship building with instructors and positive framing were positively related to subsequent student-university fit, while student-university fit was positively related to subsequent relationship building with instructors, general socializing, and positive framing. Both relationship building with instructors and positive framing had reciprocal relationships with student-university fit. Theoretical and practical implications were discussed.
•We examine lagged reciprocal relationships between student-university fit and proactive socialization behaviors.•Student-university fit related to relationship building with instructors, general socializing, and positive framing.•Relationship building with instructors and positive framing related to subsequent perceptions of student-university fit.
Injury or disease in the somatosensory nervous system may cause broad molecular changes and lead to neuropathic pain. Excitatory synaptic transmission in somatosensory pathways conveys the ...somatosensory information from the peripheral to the central nervous system. Long‐term effects of excitatory synaptic transmission on the pain pathway contribute to neuropathic pain hypersensitivity. Synaptic strength is dynamically regulated and undergoes bidirectional changes, manifested by two primary forms of synaptic plasticity, long‐term potentiation and long‐term depression (LTD), which are mediated by insertion and endocytosis of amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors (AMPARs), respectively. Molecular mechanisms of LTP have been extensively studied; on the other hand, the role of AMPAR endocytosis in the pain‐related synaptic enhancement is less well known. Recent research in the anterior cingulate cortex reveals that loss of LTD contributes to the maintenance of neuropathic pain, which provides the novel perspective of the mechanism of LTD also being critical for maintaining neuropathic pain. More importantly, exploring the molecular mechanism of LTD may help with the development of novel analgesic strategies to manage neuropathic pain.
Nerve injury can induce long‐lasting effects on excitatory synaptic transmissions of the pain pathway. Excitatory synaptic strength is dynamically regulated by the assembly and endocytosis of amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors (AMPARs). Nerve injury leads to downregulation of caspase 3 (Casp3) in the anterior cingulate cortex, which in turn abates the induction of long‐term depression (LTD). Overexpression of Casp3 restores AMPAR endocytosis and LTD induction. Targeting the molecular mechanism underlying LTD may aid in the relief of pain hypersensitivity.
Abstract Micropatterns of arginine–glycine–aspartic acid (RGD) on poly(ethylene glycol) (PEG) hydrogels were fabricated. Under an appropriate size of microislands on this strong and persistent ...non-fouling background, single mesenchymal stem cells (MSCs) from rats were well localized, keeping the same adhesive area but different shapes. The cell shapes influenced the differentiation of MSCs, and the osteogenic and adipogenic differentiations exhibited different trends. According to comparison between square and rectangular cells, optimal adipogenic differentiation occurred at aspect ratio (AR) 1, but the optimal osteogenic differentiation was found when AR was about 2. We further interpreted the optimal ratios as reflecting the inherent global anisotropy of free adipoblasts and osteoblasts on unpatterned culture plates. According to comparison between globally isotropic circular, square, triangular, and star cells, the optimal adipogenic and osteogenic differentiations happened in circular and star cells, respectively. In this case we found that extents of both adipogenic and osteogenic differentiations were linearly related to cell perimeter, which reflects the non-roundness or local anisotropy of cells. Hence, the present study makes semi-quantitative investigations of the effects of cell shape on differentiation of stem cells based on a material technique, and reveals that the shape anisotropy is very important in directing the lineage commitments of stem cells.
Primary familial brain calcification (PFBC) is a genetically heterogeneous disorder characterized by bilateral calcifications in the basal ganglia and other brain regions. The genetic basis of this ...disorder remains unknown in a significant portion of familial cases. Here, we reported a recessive causal gene, MYORG, for PFBC. Compound heterozygous or homozygous mutations of MYORG co-segregated completely with PFBC in six families, with logarithm of odds (LOD) score of 4.91 at the zero recombination fraction. In mice, Myorg mRNA was expressed specifically in S100β-positive astrocytes, and knockout of Myorg induced the formation of brain calcification at 9 months of age. Our findings provide strong evidence that loss-of-function mutations of MYORG cause brain calcification in humans and mice.
•MYORG is a major causal gene for autosomal recessive PFBC•Specific expression of MYORG suggests astrocyte involves in PFBC•Myorg knockout mice develops calcium deposits in the brain
Yao et al. provide evidence that MYORG is a major causal gene for autosomal recessive PFBC by a comprehensive strategy combining whole-exome sequencing analysis, Sanger sequencing, linkage analysis, RNA expression analysis, and a mouse model.