There is much interest in developing synthetic analogues of biological membrane channels with high efficiency and exquisite selectivity for transporting ions and molecules. Bottom-up and top-down methods can produce nanopores of a size comparable to that of endogenous protein channels, but replicating their affinity and transport properties remains challenging. In principle, carbon nanotubes (CNTs) should be an ideal membrane channel platform: they exhibit excellent transport properties and their narrow hydrophobic inner pores mimic structural motifs typical of biological channels. Moreover, simulations predict that CNTs with a length comparable to the thickness of a lipid bilayer membrane can self-insert into the membrane. Functionalized CNTs have indeed been found to penetrate lipid membranes and cell walls, and short tubes have been forced into membranes to create sensors, yet membrane transport applications of short CNTs remain underexplored. Here we show that short CNTs spontaneously insert into lipid bilayers and live cell membranes to form channels that exhibit a unitary conductance of 70-100 picosiemens under physiological conditions. Despite their structural simplicity, these 'CNT porins' transport water, protons, small ions and DNA, stochastically switch between metastable conductance substates, and display characteristic macromolecule-induced ionic current blockades. We also show that local channel and membrane charges can control the conductance and ion selectivity of the CNT porins, thereby establishing these nanopores as a promising biomimetic platform for developing cell interfaces, studying transport in biological channels, and creating stochastic sensors.

The prognostic role of inflammation index like neutrophil-to-lymphocyte ratio (NLR) in colorectal cancer (CRC) remains controversial. We conduct a meta-analysis to determine the predictable value of NLR in the clinical outcome of CRC patients. The analysis was carried out based on the data from 16 studies (19 cohorts) to evaluate the association between NLR and overall survival (OS) and progression-free survival (PFS) in patients with CRC. In addition, the relationship between NLR and clinicopathological parameters was assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that elevated pretreatment NLR predicted poorer OS (HR: 1.813, 95% CI: 1.499-2.193) and PFS (HR: 2.102, 95% CI: 1.554-2.843) in patients with CRC. Increased NLR is also significantly associated with the poorer differentiation of the tumor (OR: 1.574, 95% CI: 1.226-2.022) and higher carcino-embryonie antigen (CEA) level (OR: 1.493, 95% CI: 1.308-1.705). By these results, we conclude that NLR gains a prognostic value for patients with CRC. NLR should be monitored in CRC patients for rational stratification of the patients and adjusting the treatment strategy.

A new magnetic resonance imaging (MRI) contrast agent based on the trimetallic nitride templated (TNT) metallofullerene, Gd 3 N@C 80 , was synthesized by a facile method in high yield. The observed longitudinal and transverse relaxivities, r 1 and r 2 , for water hydrogens in the presence of the watersoluble gadofullerene 2, Gd 3 N@C 80 (OH)~2 6 (CH 2 CH 2 COOM)~1 6 (M = Na or H), are 207 and 282 mM -1 s -1 (per C 80 cage) at 2.4 T, respectively; these values are 50 times larger than those of Gd 3+ poly(aminocarboxylate) complexes, such as commercial Omniscan ® and Magnevist ® . This high 1 H relaxivity for this new hydroxylated and carboxylated gadofullerene derivative provides high signal enhancement at significantly lower Gd concentration as demonstrated by in vitro and in vivo MRI studies. Dynamic light scattering data reveal a unimodal size distribution with an average hydrodynamic radius of ca. 78 nm in pure water (pH = 7), which is significantly different from other hydroxylated or carboxylated fullerene and metallofullerene derivatives reported to date. Agarose gel infusion results indicate that the gadofullerene 2 displayed diffusion properties different from that of commercial Omniscan ® and those of PEG5000 modified Gd 3 N@C 80 . The reactive carboxyl functionality present on this highly efficient contrast agent may also serve as a precursor for biomarker tissue-targeting purposes.

The water soluble poly(ethylene glycol) (PEG) functionalized and hydroxylated endohedral trimetallic nitride metallofullerene derivatives, Gd 3 N@C 80 [DiPEG(OH)

The phytohormone ethylene is a key signaling molecule that regulates a variety of developmental processes and stress responses in plants. Transcriptional modulation is a pivotal process controlling ethylene synthesis, which further triggers the expression of stress-related genes and plant adaptation to stresses; however, it is unclear how this process is transcriptionally modulated in rice. In the present research, we report the transcriptional regulation of a novel rice ethylene response factor (ERF) in ethylene synthesis and drought tolerance. Through analysis of transcriptional data, one of the drought-responsive ERF genes, OsDERF1, was identified for its activation in response to drought, ethylene and abscisic acid. Transgenic plants overexpressing OsDERF1 (OE) led to reduced tolerance to drought stress in rice at seedling stage, while knockdown of OsDERF1 (RI) expression conferred enhanced tolerance at seedling and tillering stages. This regulation was supported by negative modulation in osmotic adjustment response. To elucidate the molecular basis of drought tolerance, we identified the target genes of OsDERF1 using the Affymetrix GeneChip, including the activation of cluster stress-related negative regulators such as ERF repressors. Biochemical and molecular approaches showed that OsDERF1 at least directly interacted with the GCC box in the promoters of ERF repressors OsERF3 and OsAP2-39. Further investigations showed that OE seedlings had reduced expression (while RI lines showed enhanced expression) of ethylene synthesis genes, thereby resulting in changes in ethylene production. Moreover, overexpression of OsERF3/OsAP2-39 suppressed ethylene synthesis. In addition, application of ACC recovered the drought-sensitive phenotype in the lines overexpressing OsERF3, showing that ethylene production contributed to drought response in rice. Thus our data reveal that a novel ERF transcriptional cascade modulates drought response through controlling the ethylene synthesis, deepening our understanding of the regulation of ERF proteins in ethylene related drought response.

No abstract

Premature drug release is a common drawback in stimuli-responsive drug delivery systems (DDS), especially if it depends on internal triggers, which are hard to control, or a single external stimulus, which can only have one function. Thus, many DDS systems have been reported that combined different triggers; however, limited success has been established in fine-tuning the release process, mainly due to the poor bioavailability and complexity of the reported designs. This paper reports the design of a hybrid microcapsule (h-MC) by a simple layer-by-layer technique comprising polysaccharides (sodium alginate, chitosan, and hyaluronic acid), iron oxide, and graphene oxide (GO). Electrostatic assembly of the oppositely charged polysaccharides and graphene sheets provided a robust structure in which to load drugs through pH control. The polysaccharide component ensured high biocompatibility, bioavailability, and tumor cells targeting. The alternative magnetic field and near-infrared laser triggerable Fe3O4@GO component provided for dual high-energy and high-penetration hyperthermia therapy. On-demand drug release from h-MC can be achieved by synchronizing these external triggers, making the release highly controllable. The synergistic effect of hyperthermia and chemotherapy was successfully confirmed in vitro and in vivo.

OsERF3 is a transcriptional repressor with an ethylene-responsive element-binding factor-associated amphiphilic repression (EAR) motif (F/LDLNxxP), which transcriptionally represses the ethylene emission and drought tolerance in rice. However, its molecular mechanism to explore repression function remains unknown. Here, we first revealed that the expression of OsERF3 was induced by drought, salt, ACC and ABA treatment. In addition, it showed a higher expression level in the root and sheath than that in the leaf. Then, we generated transgenic rice overexpressing full-length OsERF3 (OE) and its mutation of EAR motif with the A 680/C substitution (mEAR), respectively. The physiological analyses showed that mEAR lines showed better drought tolerance and more ethylene emission compared with those of OE lines and wild type plants. Consistent with our previous research, the expression of ethylene synthesis genes, including ACO2, ACS2, and ACS6 was down-regulated in OE lines. However, the repression of OsERF3 was eliminated in mEAR lines. Specifically, ACS2 was up-regulated in mEAR lines compared with that in OE lines and WT plants, suggesting that the Leu/Ala substitution within the EAR motif resulted in loss of repression of OsERF3. Thus, our data reveal that the EAR motif is required for OsERF3 to transcriptionally regulate the ethylene synthesis and drought tolerance in rice, providing new insight to the roles of ethylene-response factor proteins in regulating ethylene biosynthesis and stress response.