Regulating Ir-O Covalency to Boost Acidic Oxygen Evolution Reaction.

The unsatisfactory oxygen evolution reaction (OER) activity of IrO2 has intensively raised the cost and energy consumption of hydrogen generation from proton exchange membrane water electrolyzers. Here, the acidic OER activity of the rutile IrO2 is significantly enhanced by the incorporation of trivalent metals (e.g., Gd, Nd, and Pr) to increase the Ir-O covalency, while the high-valence (pentavalent or higher) metal incorporation decreases the Ir-O covalency resulting in worse OER activity. Experimental and theoretical analyses indicate that enhanced Ir-O covalency activates lattice oxygen and triggers lattice oxygen-mediated mechanism to enhance OER kinetics, which is verified by the finding of a linear relationship between the natural logarithm of intrinsic activity and Ir-O covalency described by charge transfer energy. By regulating the Ir-O covalency, the obtained Gd-IrO2-δ merely needs 260 mV of overpotential to reach 10 mA cm-2 and shows impressive stability during a 200-h test in 0.5 м H2SO4. This work provides an effective strategy for significantly enhancing the OER activity of the widely used IrO2 electrocatalysts through the rational regulation of Ir-O covalency.

PPARα alleviates iron overload-induced ferroptosis in mouse liver.

Ferroptosis is an iron-dependent form of non-apoptotic cell death implicated in liver, brain, kidney, and heart pathology. How ferroptosis is regulated remains poorly understood. Here, we show that PPARα suppresses ferroptosis by promoting the expression of glutathione peroxidase 4 (Gpx4) and by inhibiting the expression of the plasma iron carrier TRF. PPARα directly induces Gpx4 expression by binding to a PPRE element within intron 3. PPARα knockout mice develop more severe iron accumulation and ferroptosis in the liver when fed a high-iron diet than wild-type mice. Ferrous iron (Fe2+ ) triggers ferroptosis via Fenton reactions and ROS accumulation. We further find that a rhodamine-based "turn-on" fluorescent probe(probe1) is suitable for the in vivo detection of Fe2+ . Probe1 displays high selectivity towards Fe2+ , and exhibits a stable response for Fe2+ with a concentration of 20 µM in tissue. Our data thus show that PPARα activation alleviates iron overload-induced ferroptosis in mouse livers through Gpx4 and TRF, suggesting that PPARα may be a promising therapeutic target for drug discovery in ferroptosis-related tissue injuries. Moreover, we identified a fluorescent probe that specifically labels ferrous ions and can be used to monitor Fe2+ in vivo.

An environmentally friendly strategy for reducing the environmental risks of heavy metals adsorbed by kaolinite.

Plenty of heavy metals (HMs) that are adsorbed on clay minerals (such as kaolinite), in addition to low molecular-weight organic acids (such as oxalic acid (OA)) with high activities, are widespread in the natural environment. In the present study, the effects of OA on the environmental behaviors of Pb2+/Cd2+ adsorbed by kaolinite have been investigated. The effectiveness and mechanisms of calcium silicate (CS) and magnesium silicate (MS) in reducing the environmental risks of the HMs have also been studied. The results showed that the releases of Pb2+/Cd2+ increased with an increasing concentration of OA. When different dosages of CS/MS were added to the aging system, a redistribution of HMs took place and the free form of Pb2+/Cd2+ decreased to very low levels. Also, the unextractable Pb2+/Cd2+ increased to high levels. Furthermore, a series of characterizations showed that the released HMs were re-captured by the CS/MS. In addition, the CS immobilized the OA in the solution during the aging process, which also facilitated an immobilization of the carbon element in the environment. In general, the present study has contributed to a further understanding of the transport behaviors of the HMs in natural environments, and of the interactions between CS (or MS), the environmental media, and the heavy metal contaminants. In addition, this study has also provided an eco-friendly strategy for an effective remediation of heavy metal pollution.

Stabilizing Highly Active Ru Sites by Electron Reservoir in Acidic Oxygen Evolution.

Proton exchange membrane water electrolysis is hindered by the sluggish kinetics of the anodic oxygen evolution reaction. RuO2 is regarded as a promising alternative to IrO2 for the anode catalyst of proton exchange membrane water electrolyzers due to its superior activity and relatively lower cost compared to IrO2. However, the dissolution of Ru induced by its overoxidation under acidic oxygen evolution reaction (OER) conditions greatly hinders its durability. Herein, we developed a strategy for stabilizing RuO2 in acidic OER by the incorporation of high-valence metals with suitable ionic electronegativity. A molten salt method was employed to synthesize a series of high-valence metal-substituted RuO2 with large specific surface areas. The experimental results revealed that a high content of surface Ru4+ species promoted the OER intrinsic activity of high-valence doped RuO2. It was found that there was a linear relationship between the ratio of surface Ru4+/Ru3+ species and the ionic electronegativity of the dopant metals. By regulating the ratio of surface Ru4+/Ru3+ species, incorporating Re, with the highest ionic electronegativity, endowed Re0.1Ru0.9O2 with exceptional OER activity, exhibiting a low overpotential of 199 mV to reach 10 mA cm-2. More importantly, Re0.1Ru0.9O2 demonstrated outstanding stability at both 10 mA cm-2 (over 300 h) and 100 mA cm-2 (over 25 h). The characterization of post-stability Re0.1Ru0.9O2 revealed that Re promoted electron transfer to Ru, serving as an electron reservoir to mitigate excessive oxidation of Ru sites during the OER process and thus enhancing OER stability. We conclude that Re, with the highest ionic electronegativity, attracted a mass of electrons from Ru in the pre-catalyst and replenished electrons to Ru under the operating potential. This work spotlights an effective strategy for stabilizing cost-effective Ru-based catalysts for acidic OER.

A Tandem-Locked Chemiluminescent Probe for Imaging of Tumor-Associated Macrophage Polarization.

Tumor-associated macrophages (TAMs) play a role in both pro- and anti-tumor functions; and the targeted polarization from M2 to M1 TAMs has become an effective therapy option. Although detection of M1 TAMs is imperative to assess cancer immunotherapeutic efficacy, existing optical probes suffer from shallow tissue penetration depth and poor specificity toward M1 TAMs. Herein, we report a tandem-locked NIR chemiluminescent (CL) probe for specific detection of M1 TAMs. Through a combined molecular engineering approach via both atomic alternation and introduction of electron-withdrawing groups, near-infrared (NIR) chemiluminophores are screened out to possess record-long emission (over 800 nm), record-high CL quantum yield (2.7 % einstein/mol), and prolonged half-life (7.7 h). Based on an ideal chemiluminophore, the tandem-locked probe (DPDGN) is developed to only activate CL signal in the presence of both tumour (γ-glutamyl transpeptidase) and M1 macrophage biomarkers (nitric oxide). Such a tandem-lock design ensures its high specificity towards M1 macrophages in the tumor microenvironment over those in normal tissues or peripheral blood. Thus, DPDGN permits noninvasive imaging and tracking of M1 TAM in the tumor of living mice during R837 treatment, showing a good correlation with ex vivo methods. This study not only reports a new molecular approach towards highly efficient chemiluminophores but also reveals the first tandem-locked CL probes for enhanced imaging specificity.

LRRC23 is a conserved component of the radial spoke that is necessary for sperm motility and male fertility in mice.

Cilia and flagella are ancient structures that achieve controlled motor functions through the coordinated interaction based on microtubules and some attached projections. Radial spokes (RSs) facilitate the beating motion of these organelles by mediating signal transduction between dyneins and a central pair (CP) of singlet microtubules. RS complex isolation from Chlamydomonas axonemes enabled the detection of 23 radial spoke proteins (RSP1-RSP23), although the roles of some radial spoke proteins remain unknown. Recently, RSP15 has been reported to be bound to the stalk of RS2, but its homolog in mammals has not been identified. Herein, we show that Lrrc23 is an evolutionarily conserved testis-enriched gene encoding an RSP15 homolog in mice. We found that LRRC23 localizes to the RS complex within murine sperm flagella and interacts with RSPH3A and RSPH3B. The knockout of Lrrc23 resulted in male infertility due to RS disorganization and impaired motility in murine spermatozoa, whereas the ciliary beating was not significantly affected. These data indicate that LRRC23 is a key regulator that underpins the integrity of the RS complex within the flagella of mammalian spermatozoa, whereas it is dispensable in cilia. This article has an associated First Person interview with the first author of the paper.

EZH2-mediated epigenetic silencing of tumor-suppressive let-7c/miR-99a cluster by hepatitis B virus X antigen enhances hepatocellular carcinoma progression and metastasis.

BACKGROUND: Hepatitis B virus (HBV)-encoded X antigen, HBx, assists in the development of hepatocellular carcinoma (HCC) through complex mechanisms. Our results provide new insights into the EZH2 epigenetic repression of let-7c that promotes HCC migration induced by HBx. Thus, let-7c and HMGA2 represent key diagnostic markers and potential therapeutic targets for the treatment of HBV-related HCC. RESULTS: We investigated the epigenetic regulation of let-7c, an important representative miRNA in liver tumor metastasis, in human HCC cells to verify the effect of HBx. Based on quantitative PCR (qPCR) of mRNA isolated from tumor and adjacent non-tumor liver tissues of 24 patients with HBV-related HCC, EZH2 expression was significantly overexpressed in most HCC tissues (87.5%). We executed a miRNA microarray analysis in paired HBV-related HCC tumor and adjacent non-tumorous liver tissue from six of these patients and identified let-7c, miR-199a-3p, and miR-99a as being downregulated in the tumor tissue. Real-time PCR analysis verified significant downregulation of let-7c and miR-99a in both HepG2X and Hep3BX cells, which stably overexpress HBx, relative to parental cells. HBX enhanced EZH2 expression and attenuated let-7c expression to induce HMGA2 expression in the HCC cells. Knockdown of HMGA2 significantly downregulated the metastatic potential of HCC cells induced by HBx. CONCLUSIONS: The deregulation of let-7c expression by HBx may indicate a potential novel pathway through deregulating cell metastasis and imply that HMGA2 might be used as a new prognostic marker and/or as an effective therapeutic target for HCC.

MiR-672-5p-Mediated Upregulation of REEP6 in Spinal Dorsal Horn Participates in Bortezomib-Induced Neuropathic Pain in Rats.

Evidence shows that miRNAs are deeply involved in nervous system diseases, but whether miRNAs contribute to the bortezomib (BTZ)-induced neuropathic pain remains unclear. We aimed to investigate whether miRNAs contribute to bortezomib (BTZ)-induced neuropathic pain and explore the related downstream cascades. The level of miRNAs in the spinal dorsal horn was explored using miRNA microarray and PCR. MiR-672-5p was significantly downregulated in dorsal horn neurons in the rats with BTZ treatment. Intrathecal injection of miR-672-5p agomir blunted the increase of the amplitude and frequency of sEPSCs in dorsal horn neurons and mechanical allodynia induced by BTZ. In addition, the knockdown of miR-672-5p by intrathecal injection of antagomir increased the amplitude and frequency of sEPSCs in dorsal horn neurons and decreased the mechanical withdrawal threshold in naïve rats. Furthermore, silico analysis and the data from subsequent assays indicated that REEP6, a potential miR-672-5p-regulating molecule, was increased in the spinal dorsal horn of rats with BTZ-induced neuropathic pain. Blocking REEP6 alleviated the mechanical pain behavior induced by BTZ, whereas overexpressing REEP6 induced pain hypersensitivity in naïve rats. Importantly, we further found that miR-672-5p was expressed in the REEP6-positive cells, and overexpression or knockdown of miR-672-5p reversely regulated the REEP6 expression. Bioinformatics analysis and double-luciferase reporter assay showed the existence of interaction sites between REEP6 mRNA and miR-672-5p. Overall, our study demonstrated that miR-672-5p directly regulated the expression of REEP6, which participated in the neuronal hyperexcitability in the spinal dorsal horn and neuropathic pain following BTZ treatment. This signaling pathway may potentially serve as a novel therapeutic avenue for chemotherapeutic-induced mechanical hypersensitivity.

Novel Cocktail Therapy Based on a Nanocarrier with an Efficient Transcytosis Property Reverses the Dynamically Deteriorating Tumor Microenvironment for Enhanced Immunotherapy.

The immune checkpoint blockade (ICB) faces a low response rate in clinical cancer treatment. Chemotherapy could enhance the response rate of the ICB, but patients would suffer from side effects. The off-target toxicity could be reduced by loading the chemotherapeutic agent through nanocarriers. Therefore, we developed a polymeric carrier for doxorubicin (DOX) loading to form DOX nanoparticles (DOX NPs), which were spatiotemporally responsive to the tumor microenvironment (TME). DOX NPs had an efficient transcytosis property for deep tumor infiltration and sustained drug release ability. Unfortunately, a binary therapy of DOX NPs and ICB induces tumor adaptive resistance and causes dynamic deterioration of the TME. We propose for the first time that TGF-ß1 is a major cause of tumor adaptive resistance and developed an immune cocktail therapy containing DOX NPs, ICB, and TGF-ß1 gene silencing nanoparticles. This therapy successfully overcame tumor adaptive resistance by reversing the immunosuppressive TME and achieved enhanced tumor treatment efficiency.

Mixed solvent fabrication of tobermorite and the fixation of heavy metals in water and soil.

Here, tobermorite was prepared by a solvothermal technology using calcite and quartz with a mixed solvent of ethanol and water. Factors including reaction temperature, time and KOH content were studied to optimize the preparation procedure. To study the relationship between ethanol content-material structural characteristics-adsorption capacity, a series of materials were prepared in different mixed solvent proportions of ethanol and water, and their structural characteristics and adsorption capacity were compared. We found that the adsorption capacity of different samples for Pb2+ and Cd2+ was positively correlated with negatively correlated with the surface area and negatively correlated with the crystallinity of materials. Then, the material prepared by 30% ethanol solution (30-T) with the best adsorption performance was used for further research; the results were fitted by kinetic and thermodynamic models, and adsorbed materials were analyzed by various characterizations, suggesting that the adsorption process was ascribed to comprehensive pathways including ion exchange, chemical precipitation, and surface-complexation. Then, the 30-T was further used to remediate heavy metals contaminated soil, and the remediation effect was examined by the DTPA-extractable method and the European Community Bureau of Reference (BCR) sequential extraction method. The DTPA-extractable results showed that tobermorite observably reduced the bioavailability of Pb and Cd, and the BCR results suggested that the acid-soluble and reducible fractions of Pb and Cd were transformed to the oxidizable and residual fractions after remediation. In summary, tobermorite has great potential in the remediation of heavy metal polluted-aquatic environment/system and soil.

Curcumin enhances p-cresyl sulfate-induced cytotoxic effects on renal tubular cells.

Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), protein-bound uremic toxins, can induce oxidative stress and cause renal disease progression. However, the different cytotoxic effects on renal cells between IS and PCS are not stated. Due to uremic toxins are generally found in CKD patients, the mechanisms of uremic toxins-induced renal injury are required to study. Curcumin has anti-oxidant, anti-inflammatory and anti-apoptotic effects which may be potential used to protect against renal damage. In contrast, curcumin also exert cytotoxic effects on various cells. In addition, curcumin may reduce or enhance cytotoxicity combined with different chemicals treatments. However, whether curcumin may influence uremic toxins-induced renal injury is unclear. The goal of this study is to compare the different cytotoxic effects on renal cells between IS and PCS treatment, as well as the synergistic or antagonistic effects by combination treatments with curcumin and PCS. Our experimental result shows the PCS exerts a stronger antiproliferative effect on renal tubular cells than IS treatment. In addition, our study firstly demonstrates that curcumin enhances PCS-induced cell cytotoxicity through caspase-dependent apoptotic pathway and cell cycle alteration.

Photothermal-Chemotherapy Enhancing Tumor Immunotherapy by Multifunctional Metal-Organic Framework Based Drug Delivery System.

Immunotherapy holds great promise for patients undergoing tumor treatment. However, the clinical effect of immunotherapy is limited because of tumor immunogenicity and its immunosuppressive microenvironment. Herein, the metal-organic framework (MIL-100) loaded with chemotherapeutic agent mitoxantrone (MTO) was combined with photothermal-chemotherapy for enhancing immunogenic cell death. MIL-100 loaded with MTO and hyaluronic acid as nanoparticles (MMH NPs) yielded an NP with two therapeutic properties (photothermal and chemotherapy) with dual imaging modes (photoacoustic and thermal). When MMH NPs were coinjected with an anti-OX40 antibody in colorectal cancer, the highest antitumor efficacy and a robust immune effect were achieved. This work provides a novel combined therapeutic strategy, which will hold great promise in future tumor therapy.

Insights into photocatalytic degradation of phthalate esters over MSnO3 perovskites (M = Mg, Ca): Experiments and density functional theory.

In this study, the physicochemical and photocatalytic properties of two kinds of stannate perovskite oxides (MgSnO3 and CaSnO3) were investigated under simulated sunlight, where dimethyl phthalate (DMP) and diethyl phthalate (DEP) were selected as the probe pollutants. The results of photochemical characterization showed that MgSnO3 perovskite exhibited better photocatalytic performance than CaSnO3 perovskite. MgSnO3 perovskite could effectively degrade 75% of DMP and 79% of DEP through pseudo-first-order reaction kinetics, which remained good in pH 3.0 to 9.0. Quenching experiments and electron paramagnetic resonance (EPR) characterization indicated that photogenerated holes (h+), superoxide (O2-), and hydroxyl radicals (OH) worked in the photo-degradation, while O2- played the most important role. Furthermore, intermediates identification and density functional theory (DFT) calculations were used to explore the degradation mechanism. For both DMP and DEP, the reactive oxygen species (ROS, including O2- and OH) were responsible for the hydroxylation of benzene ring and the breaking of the aliphatic chain, while h+ was prone to break the aliphatic chain. This work is expected to provide new insights on the photocatalytic mechanism of stannate perovskites for environmental remediation.

NucMap: a database of genome-wide nucleosome positioning map across species.

Dynamics of nucleosome positioning affects chromatin state, transcription and all other biological processes occurring on genomic DNA. While MNase-Seq has been used to depict nucleosome positioning map in eukaryote in the past years, nucleosome positioning data is increasing dramatically. To facilitate the usage of published data across studies, we developed a database named nucleosome positioning map (NucMap, http://bigd.big.ac.cn/nucmap). NucMap includes 798 experimental data from 477 samples across 15 species. With a series of functional modules, users can search profile of nucleosome positioning at the promoter region of each gene across all samples and make enrichment analysis on nucleosome positioning data in all genomic regions. Nucleosome browser was built to visualize the profiles of nucleosome positioning. Users can also visualize multiple sources of omics data with the nucleosome browser and make side-by-side comparisons. All processed data in the database are freely available. NucMap is the first comprehensive nucleosome positioning platform and it will serve as an important resource to facilitate the understanding of chromatin regulation.

Gut-Microbial Metabolites, Probiotics and Their Roles in Type 2 Diabetes.

Type 2 diabetes (T2D) is a worldwide prevalent metabolic disorder defined by high blood glucose levels due to insulin resistance (IR) and impaired insulin secretion. Understanding the mechanism of insulin action is of great importance to the continuing development of novel therapeutic strategies for the treatment of T2D. Disturbances of gut microbiota have been widely found in T2D patients and contribute to the development of IR. In the present article, we reviewed the pathological role of gut microbial metabolites including gaseous products, branched-chain amino acids (BCAAs) products, aromatic amino acids (AAAs) products, bile acids (BA) products, choline products and bacterial toxins in regulating insulin sensitivity in T2D. Following that, we summarized probiotics-based therapeutic strategy for the treatment of T2D with a focus on modulating gut microbiota in both animal and human studies. These results indicate that gut-microbial metabolites are involved in the pathogenesis of T2D and supplementation of probiotics could be beneficial to alleviate IR in T2D via modulation of gut microbiota.

Noninvasive prenatal testing for chromosome aneuploidies and subchromosomal microdeletions/microduplications in a cohort of 8141 single pregnancies.

BACKGROUND: Noninvasive prenatal testing (NIPT) for fetal aneuploidies by scanning cell-free fetal DNA in maternal plasma is rapidly becoming a first-tier aneuploidy screening test in clinical practices. With the development of whole-genome sequencing technology, small subchromosomal deletions and duplications that could not be detected by conventional karyotyping are now able to be detected with NIPT technology. METHODS: In the present study, we examined 8141 single pregnancies with NIPT to calculate the positive predictive values of each of the chromosome aneuploidies and the subchromosomal microdeletions and microduplications. RESULTS: We confirmed that the positive predictive values (PPV) for trisomy 13, trisomy 18, trisomy 21, and sex chromosome aneuploidy were 14.28%, 60%, 80%, and 45.83%, respectively. At the same time, we also found 51 (0.63%) positive cases for chromosomal microdeletions or microduplications but only 13 (36.11%) true-positive cases. These results indicate that NIPT for trisomy 21 detection had the highest accuracy, while accuracy was low for chromosomal microdeletion and microduplications. CONCLUSIONS: Therefore, it is very important to improve the specificity, accuracy, and sensitivity of NIPT technology for the detection of subchromosomal microdeletions and microduplications.

Platelet-Rich Plasma Promotes Spinal Ligament Healing after Injury.

BACKGROUND: Spinal ligament injury is often a comorbidity in spine fracture. Although the spinal ligament is important to maintain spinal stability, little is done to improve its healing after injury. Platelet-rich plasma (PRP) has been shown effective in treating many tendon and ligament disorders, but its role in spinal ligament injury remains to be evaluated. METHODS: Supraspinous ligament and interspinous ligament were cut in rabbits to simulate spinal ligament injury after spine fracture. After the injury, the administration of autologous PRP was performed and compared with saline injection control. Morphology and histological analysis were utilized to assess PRP effect and compare it to the saline control group. To understand potential molecular mechanisms of PRP on ligamentous healing, bioinfor-matics analysis of the microarray dataset (GSE70918) from the Gene Expression Omnibus database was conducted. RESULTS: The PRP group was more likely to have a better appearance both morphologically and histologically than did the saline control group. Pathway analysis determined that IL-17 signaling pathway and TNF signaling pathway were the two significantly induced signaling pathways in tendon fibroblasts treated by PRP. In the protein-protein interaction network analysis, interleukin 6 had the highest degrees of connectivity. CONCLUSIONS: PRP improves spinal ligament healing through the activation of pathways related to inflammation. Further studies are required to determine the dosing and timing of PRP administration to achieve better longterm treatment outcome.

TGM6 variants in Parkinson's disease: clinical findings and functional evidence.

TGM6 encodes transglutaminase 6, which catalyzes the covalent crosslinking of proteins through transamination reactions. Variants in TGM6 have been identified as the cause of spinocerebellar ataxia type 35. However, we found 12 TGM6 variants of low frequency among 308 patients with Parkinson's disease using next-generation sequencing technologies and multiple ligation-dependent probe amplification, including two variants TGM6 p.R111C and p.L517W, which have been reported to affect functions of transglutaminase 6 in spinocerebellar ataxia type 35 cases. The characteristics of these TGM6 carriers were summarized. To clarify the role of TGM6 variants in Parkinson's disease, we constructed the plasmids of wild-type TGM6 and TGM6 p.R111C, p.P359L, p.L517W to transfect A53T-SH-SY5Y cells and conducted transglutaminase assay, western blots, immunofluorescence, and cell viability assay. Results revealed that the distribution and expression levels of transglutaminase 6 were not affected by TGM6 variants. However, the variants showed lower transglutaminase activity than wild-type transglutaminase 6. The overexpression of wild-type TGM6 was proved to relieve the cell damage, down-regulate the level of α-synuclein and enhance autophagy. These effects were weakened in cells transfected with mutant TGM6 plasmids. Our results suggested that there may be some relationship between TGM6 and Parkinson's disease. TGM6 carriers in Parkinson's disease patients presented with typical parkinsonism but progressed slower. The high expression level of wild-type transglutaminase 6 may protect cells by decreasing α-synuclein and enhancing autophagy.

Tumor microenvironment as the "regulator" and "target" for gene therapy.

In this review, we focus on strategies for designing functional nano gene carriers, as well as choosing therapeutic genes targeting the tumor microenvironment. Gene mutations have a great impact on the occurrence of cancer. Thus, gene therapy plays a major role in cancer therapy and has the potential to cure cancer. Well-designed gene therapy largely relies on effective gene carriers, which can be divided into viral carriers and non-viral carriers. A gene carrier delivers functional genes to their intracellular target and avoids nucleic acids being degraded by nucleases in the serum. Most conventional cancer gene therapies only target cancer cells and do not appear to be sufficintly efficient to pass clinical trials. Accumulating evidence has shown that extending the therapeutic strategies to the tumor microenvironment, rather than the tumor cell itself, can allow more options for achieving robust anti-cancer efficiency. In addition, unusual features between tumor microenvironment and normal tissues, such as a lower pH, higher glutathione and reactive oxygen species concentrations, and overexpression of some enzymes, facilitate the design of smart stimuli-responsive gene carriers regulated by the tumor microenvironment. These carriers interact with nucleic acids and then form stable nanoparticles under physiological conditions. By regulation of the tumor microenvironment, stimuli-responsive gene carriers are able to change their properties and achieve high gene delivery efficiency. Considering the tumor microenvironment as the "regulator" and "target" when designing gene carriers and choosing therapeutic genes shows significant benefit with respect to improving the accuracy and efficiency of cancer gene therapy.

MTD: a mammalian transcriptomic database to explore gene expression and regulation.

A systematic transcriptome survey is essential for the characterization and comprehension of the molecular basis underlying phenotypic variations. Recently developed RNA-seq methodology has facilitated efficient data acquisition and information mining of transcriptomes in multiple tissues/cell lines. Current mammalian transcriptomic databases are either tissue-specific or species-specific, and they lack in-depth comparative features across tissues and species. Here, we present a mammalian transcriptomic database (MTD) that is focused on mammalian transcriptomes, and the current version contains data from humans, mice, rats and pigs. Regarding the core features, the MTD browses genes based on their neighboring genomic coordinates or joint KEGG pathway and provides expression information on exons, transcripts and genes by integrating them into a genome browser. We developed a novel nomenclature for each transcript that considers its genomic position and transcriptional features. The MTD allows a flexible search of genes or isoforms with user-defined transcriptional characteristics and provides both table-based descriptions and associated visualizations. To elucidate the dynamics of gene expression regulation, the MTD also enables comparative transcriptomic analysis in both intraspecies and interspecies manner. The MTD thus constitutes a valuable resource for transcriptomic and evolutionary studies. The MTD is freely accessible at http://mtd.cbi.ac.cn.