Human gut bacteria produce ΤΗ17-modulating bile acid metabolites.

The microbiota modulates gut immune homeostasis. Bacteria influence the development and function of host immune cells, including T helper cells expressing interleukin-17A (TH17 cells). We previously reported that the bile acid metabolite 3-oxolithocholic acid (3-oxoLCA) inhibits TH17 cell differentiation1. Although it was suggested that gut-residing bacteria produce 3-oxoLCA, the identity of such bacteria was unknown, and it was unclear whether 3-oxoLCA and other immunomodulatory bile acids are associated with inflammatory pathologies in humans. Here we identify human gut bacteria and corresponding enzymes that convert the secondary bile acid lithocholic acid into 3-oxoLCA as well as the abundant gut metabolite isolithocholic acid (isoLCA). Similar to 3-oxoLCA, isoLCA suppressed TH17 cell differentiation by inhibiting retinoic acid receptor-related orphan nuclear receptor-γt, a key TH17-cell-promoting transcription factor. The levels of both 3-oxoLCA and isoLCA and the 3α-hydroxysteroid dehydrogenase genes that are required for their biosynthesis were significantly reduced in patients with inflammatory bowel disease. Moreover, the levels of these bile acids were inversely correlated with the expression of TH17-cell-associated genes. Overall, our data suggest that bacterially produced bile acids inhibit TH17 cell function, an activity that may be relevant to the pathophysiology of inflammatory disorders such as inflammatory bowel disease.

Author Correction: Bile acid metabolites control TH17 and Treg cell differentiation.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

The MpNAC72/MpERF105-MpMYB10b module regulates anthocyanin biosynthesis in Malus 'Profusion' leaves infected with Gymnosporangium yamadae.

Apple rust is a serious fungal disease affecting Malus plants worldwide. Infection with the rust pathogen Gymnosporangium yamadae induces the accumulation of anthocyanins in Malus to resist rust disease. However, the mechanism of anthocyanin biosynthesis regulation in Malus against apple rust is still unclear. Here, we show that MpERF105 and MpNAC72 are key regulators of anthocyanin biosynthesis via the ethylene-dependent pathway in M. 'Profusion' leaves under rust disease stress. Exogenous ethephon treatment promoted high expression of MpERF105 and MpNAC72 and anthocyanin accumulation in G. yamadae-infected M. 'Profusion' leaves. Overexpression of MpERF105 increased the total anthocyanin content of Malus plant material and acted by positively regulating its target gene, MpMYB10b. MpNAC72 physically interacted with MpERF105 in vitro and in planta, and the two form a protein complex. Coexpression of the two leads to higher transcript levels of MpMYB10b and higher anthocyanin accumulation. In addition, overexpression of MpERF105 or MpNAC72 enhanced the resistance of M. 'Profusion' leaves to apple rust. In conclusion, our results elucidate the mechanism by which MpERF105 and MpNAC72 are induced by ethylene in G. yamadae-infected M. 'Profusion' leaves and promote anthocyanin accumulation by mediating the positive regulation of MpMYB10b expression.

Bile acid metabolites control TH17 and Treg cell differentiation.

Bile acids are abundant in the mammalian gut, where they undergo bacteria-mediated transformation to generate a large pool of bioactive molecules. Although bile acids are known to affect host metabolism, cancer progression and innate immunity, it is unknown whether they affect adaptive immune cells such as T helper cells that express IL-17a (TH17 cells) or regulatory T cells (Treg cells). Here we screen a library of bile acid metabolites and identify two distinct derivatives of lithocholic acid (LCA), 3-oxoLCA and isoalloLCA, as T cell regulators in mice. 3-OxoLCA inhibited the differentiation of TH17 cells by directly binding to the key transcription factor retinoid-related orphan receptor-γt (RORγt) and isoalloLCA increased the differentiation of Treg cells through the production of mitochondrial reactive oxygen species (mitoROS), which led to increased expression of FOXP3. The isoalloLCA-mediated enhancement of Treg cell differentiation required an intronic Foxp3 enhancer, the conserved noncoding sequence (CNS) 3; this represents a mode of action distinct from that of previously identified metabolites that increase Treg cell differentiation, which require CNS1. The administration of 3-oxoLCA and isoalloLCA to mice reduced TH17 cell differentiation and increased Treg cell differentiation, respectively, in the intestinal lamina propria. Our data suggest mechanisms through which bile acid metabolites control host immune responses, by directly modulating the balance of TH17 and Treg cells.

Characterization and gene expression analysis reveal universal stress proteins respond to abiotic stress in Gossypium hirsutum.

BACKGROUND: Universal stress proteins (USPs) are a class of stress-induced proteins that play a crucial role in biotic and abiotic stress responses. These proteins have previously been reported to participate directly in responses to various stress and protect plants against unfavorable environmental conditions. However, there is limited research on USPs in cotton, and systematic characterization of USPs in Gossypium species is lacking. RESULTS: In the present study, the USP genes in Gossypium hirsutum were systematically identified and classified into six distinct subfamilies. The expansion of USPs in Gossypium species is mainly caused by dispersed duplication and whole genome duplication. Notably, the USPs that have expanded through allotetraploidization events are highly conserved in the allotetraploid species. The promoter regions of GhUSPs contain a diverse range of cis-acting elements associated with stress response. The RNA-Seq analysis and RT-qPCR assays revealed a significant induction of numerous GhUSPs expressions in response to various abiotic stresses. The co-expression network of GhUSPs revealed their involvement in stress response. CONCLUSIONS: This study systematically analyzed the biological characteristics of GhUSPs and their response to abiotic stress. These findings serve as a theoretical basis for facilitating the breeding of cotton varieties in future research.

Studying the Interaction between Bendamustine and DNA Molecule with SERS Based on AuNPs/ZnCl2/NpAA Solid-State Substrate.

Bendamustine (BENDA) is a bifunctional alkylating agent with alkylating and purinergic antitumor activity, which exerts its anticancer effects by direct binding to DNA, but the detailed mechanism of BENDA-DNA interaction is poorly understood. In this paper, the interaction properties of the anticancer drug BENDA with calf thymus DNA (ctDNA) were systematically investigated based on surface-enhanced Raman spectroscopy (SERS) technique mainly using a novel homemade AuNPs/ZnCl2/NpAA (NpAA: nano porous anodic alumina) solid-state substrate and combined with ultraviolet-visible spectroscopy and molecular docking simulation to reveal the mechanism of their interactions. We experimentally compared and studied the SERS spectra of ctDNA, BENDA, and BENDA-ctDNA complexes with different molar concentrations (1:1, 2:1, 3:1), and summarized their important characteristic peak positions, their peak position differences, and hyperchromic/hypochromic effects. The results showed that the binding modes include covalent binding and hydrogen bonding, and the binding site of BENDA to DNA molecules is mainly the N7 atom of G base. The results of this study help to understand and elucidate the mechanism of BENDA at the single-molecule level, and provide guidance for the further development of effective new drugs with low toxicity and side effects.

Development of a covalent inhibitor of gut bacterial bile salt hydrolases.

Bile salt hydrolase (BSH) enzymes are widely expressed by human gut bacteria and catalyze the gateway reaction leading to secondary bile acid formation. Bile acids regulate key metabolic and immune processes by binding to host receptors. There is an unmet need for a potent tool to inhibit BSHs across all gut bacteria to study the effects of bile acids on host physiology. Here, we report the development of a covalent pan-inhibitor of gut bacterial BSHs. From a rationally designed candidate library, we identified a lead compound bearing an alpha-fluoromethyl ketone warhead that modifies BSH at the catalytic cysteine residue. This inhibitor abolished BSH activity in conventional mouse feces. Mice gavaged with a single dose of this compound displayed decreased BSH activity and decreased deconjugated bile acid levels in feces. Our studies demonstrate the potential of a covalent BSH inhibitor to modulate bile acid composition in vivo.

The risk factors for deep venous thrombosis in critically ill older adult patients: a subgroup analysis of a prospective, multicenter, observational study.

BACKGROUND: Older adult patients mainly suffer from multiple comorbidities and are at a higher risk of deep venous thrombosis (DVT) during their stay in the intensive care unit (ICU) than younger adult patients. This study aimed to analyze the risk factors for DVT in critically ill older adult patients. METHODS: This was a subgroup analysis of a prospective, multicenter, observational study of patients who were admitted to the ICU of 54 hospitals in Zhejiang Province from September 2019 to January 2020 (ChiCTR1900024956). Patients aged > 60 years old on ICU admission were included. The primary outcome was DVT during the ICU stay. The secondary outcomes were the 28- and 60-day survival rates, duration of stay in ICU, length of hospitalization, pulmonary embolism, incidence of bleeding events, and 60-day coagulopathy. RESULTS: A total of 650 patients were finally included. DVT occurred in 44 (2.3%) patients. The multivariable logistic regression analysis showed that age (≥75 vs 60-74 years old, odds ratio (OR) = 2.091, 95% confidence interval (CI): 1.308-2.846, P = 0.001), the use of analgesic/sedative/muscarinic drugs (OR = 2.451, 95%CI: 1.814-7.385, P = 0.011), D-dimer level (OR = 1.937, 95%CI: 1.511-3.063, P = 0.006), high Caprini risk score (OR = 2.862, 95%CI: 1.321-2.318, P = 0.039), basic prophylaxis (OR = 0.111, 95%CI: 0.029-0.430, P = 0.001), and physical prophylaxis (OR = 0.322, 95%CI: 0.109-0.954, P = 0.041) were independently associated with DVT. There were no significant differences in 28- and 60-day survival rates, duration of stay in ICU, total length of hospitalization, 60-day pulmonary embolism, and coagulation dysfunction between the two groups, while the DVT group had a higher incidence of bleeding events (2.6% vs. 8.9%, P < 0.001). CONCLUSION: In critically ill older adult patients, basic prophylaxis and physical prophylaxis were found as independent protective factors for DVT. Age (≥75 years old), the use of analgesic/sedative/muscarinic drugs, D-dimer level, and high Caprini risk score were noted as independent risk factors for DVT. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900024956).URL: http://www.chictr.org.cn/listbycreater.aspx .

3D Electron-Rich ZIF-67 Coordination Compounds Based on 2-Methylimidazole: Synthesis, Characterization and Effect on Thermal Decomposition of RDX, HMX, CL-20, DAP-4 and AP.

ZIF-67 is a three-dimensional zeolite imidazole ester framework material with a porous rhombic dodecahedral structure, a large specific surface area and excellent thermal stability. In this paper, the catalytic effect of ZIF-67 on five kinds of energetic materials, including RDX, HMX, CL-20, AP and the new heat-resistant energetic compound DAP-4, was investigated. It was found that when the mass fraction of ZIF-67 was 2%, it showed excellent performance in catalyzing the said compounds. Specifically, ZIF-67 reduced the thermal decomposition peak temperatures of RDX, HMX, CL-20 and DAP-4 by 22.3 °C, 18.8 °C, 4.7 °C and 10.5 °C, respectively. In addition, ZIF-67 lowered the low-temperature and high-temperature thermal decomposition peak temperatures of AP by 27.1 °C and 82.3 °C, respectively. Excitingly, after the addition of ZIF-67, the thermal decomposition temperature of the new heat-resistant high explosive DAP-4 declined by approximately 10.5 °C. In addition, the kinetic parameters of the RDX+ZIF-67, HMX+ZIF-67, CL-20+ZIF-67 and DAP-4+ZIF-67 compounds were analyzed. After the addition of the ZIF-67 catalyst, the activation energy of the four energetic materials decreased, especially HMX+ZIF-67, whose activation energy was approximately 190 kJ·mol-1 lower than that reported previously for HMX. Finally, the catalytic mechanism of ZIF-67 was summarized. ZIF-67 is a potential lead-free, green, insensitive and universal EMOFs-based energetic burning rate catalyst with a bright prospect for application in solid propellants in the future.

[Change in serum IgG antibody during the recovery stage of Omicron variant infection in children: an analysis of 110 cases]. / 110ä¾‹å„¿ç«¥å¥¥å¯†å ‹æˆŽå˜å¼‚æ ªæ„ŸæŸ“æ¢å¤æœŸè¡€æ¸ IgG抗体变化.

OBJECTIVES: To investigate the serum level of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific RBD IgG antibody (SARS-CoV-2 IgG antibody for short) in children with SARS-CoV-2 Omicron variant infection during the recovery stage, as well as the protective effect of SARS-CoV-2 vaccination against Omicron infection. METHODS: A retrospective analysis was performed on 110 children who were diagnosed with coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 Omicron variant infection in Tianjin of China from January 8 to February 7, 2022. According to the status of vaccination before diagnosis, they were divided into a booster vaccination (3 doses) group with 2 children, a complete vaccination (2 doses) group with 90 children, an incomplete vaccination (1 dose) group with 5 children, and a non-vaccination group with 13 children. The clinical data and IgG level were compared among the 4 groups. RESULTS: The complete vaccination group had a significantly higher age than the non-vaccination group at diagnosis (P<0.05), and there was a significant difference in the route of transmission between the two groups (P<0.05). There were no significant differences among the four groups in sex, clinical classification, and re-positive rate of SARS-CoV-2 nucleic acid detection (P>0.05). All 97 children were vaccinated with inactivated vaccine, among whom 85 children (88%) were vaccinated with BBIBP-CorV Sinopharm vaccine (Beijing Institute of Biological Products, Beijing, China). At 1 month after diagnosis, the booster vaccination group and the complete vaccination group had a significantly higher level of SARS-CoV-2 IgG antibody than the non-vaccination group (P<0.05), and at 2 months after diagnosis, the complete vaccination group had a significantly higher level of SARS-CoV-2 IgG antibody than the non-vaccination group (P<0.05). For the complete vaccination group, the level of SARS-CoV-2 IgG antibody at 2 months after diagnosis was significantly lower than that at 1 month after diagnosis (P<0.05). CONCLUSIONS: Vaccination with inactivated SARS-CoV-2 vaccine has a protective effect against Omicron infection in children. For children vaccinated with 2 doses of the vaccine who experience Omicron infection, there may be a slight reduction in the level of SARS-CoV-2 IgG antibody at 2 months after diagnosis. Citation:Chinese Journal of Contemporary Pediatrics, 2022, 24(7): 736-741.

Momentum contrastive learning for few-shot COVID-19 diagnosis from chest CT images.

The current pandemic, caused by the outbreak of a novel coronavirus (COVID-19) in December 2019, has led to a global emergency that has significantly impacted economies, healthcare systems and personal wellbeing all around the world. Controlling the rapidly evolving disease requires highly sensitive and specific diagnostics. While RT-PCR is the most commonly used, it can take up to eight hours, and requires significant effort from healthcare professionals. As such, there is a critical need for a quick and automatic diagnostic system. Diagnosis from chest CT images is a promising direction. However, current studies are limited by the lack of sufficient training samples, as acquiring annotated CT images is time-consuming. To this end, we propose a new deep learning algorithm for the automated diagnosis of COVID-19, which only requires a few samples for training. Specifically, we use contrastive learning to train an encoder which can capture expressive feature representations on large and publicly available lung datasets and adopt the prototypical network for classification. We validate the efficacy of the proposed model in comparison with other competing methods on two publicly available and annotated COVID-19 CT datasets. Our results demonstrate the superior performance of our model for the accurate diagnosis of COVID-19 based on chest CT images.

CsSWEET1a and CsSWEET17 Mediate Growth and Freezing Tolerance by Promoting Sugar Transport across the Plasma Membrane.

Sugars Will Eventually be Exported Transporters (SWEETs) are important in plant biological processes. Expression levels of CsSWEET1a and CsSWEET17 are induced by cold acclimation (CA) and cold stress in Camellia sinensis. Here, we found that CsSWEET17 was alternatively spliced, and its exclusion (Ex) transcript was associated with the CA process. Both plasma membrane-localized CsSWEET1a and CsSWEET17 transport hexoses, but cytoplasm-localized CsSWEET17-Ex does not. These results indicate that alternative splicing may be involved in regulating the function of SWEET transporters in response to low temperature in plants. The extra C-terminal of CsSWEET17, which is not found in the tonoplast fructose transporter AtSWEET17, did not affect its plasma membrane localization but promoted its sugar transport activities. The overexpression (OE) of CsSWEET1a and CsSWEET17 genes resulted in an increased sugar uptake in Arabidopsis, affecting plant germination and growth. The leaf and seed sizes of the CsSWEET17-OE lines were significantly larger than those of the wild type. Moreover, the OE of CsSWEET1a and CsSWEET17 significantly reduced the relative electrolyte leakage levels under freezing stress. Compared with the wild type, the expression of AtCWINV genes was suppressed in both CsSWEET1a-OE and CsSWEET17-OE lines, indicating the alteration in sugar contents in the cell walls of the OE lines. Furthermore, the interaction between CsSWEET1a and CsSWEET17 was confirmed using yeast two-hybrid and bimolecular fluorescence complementation assays. We showed that CsSWEET1a and CsSWEET17 form homo-/heterodimers in the plasma membrane and mediate the partitioning of sugars between the cytoplasm and the apoplast, thereby regulating plant growth and freezing tolerance.

ABA-dependent bZIP transcription factor, CsbZIP18, from Camellia sinensis negatively regulates freezing tolerance in Arabidopsis.

KEY MESSAGE: Overexpression of the tea plant gene CsbZIP18 in Arabidopsis impaired freezing tolerance, and CsbZIP18 is a negative regulator of ABA signaling and cold stress. Basic region/leucine zipper (bZIP) transcription factors play important roles in the abscisic acid (ABA) signaling pathway and abiotic stress response in plants. However, few bZIP transcription factors have been functionally characterized in tea plants (Camellia sinensis). In this study, a bZIP transcription factor, CsbZIP18, was found to be strongly induced by natural cold acclimation, and the expression level of CsbZIP18 was lower in cold-resistant cultivars than in cold-susceptible cultivars. Compared with wild-type (WT) plants, Arabidopsis plants constitutively overexpressing CsbZIP18 exhibited decreased sensitivity to ABA, increased levels of relative electrolyte leakage (REL) and reduced values of maximal quantum efficiency of photosystem II (Fv/Fm) under freezing conditions. The expression of ABA homeostasis- and signal transduction-related genes and abiotic stress-inducible genes, such as RD22, RD26 and RAB18, was suppressed in overexpression lines under freezing conditions. However, there was no significant change in the expression of genes involved in the C-repeat binding factor (CBF)-mediated ABA-independent pathway between WT and CsbZIP18 overexpression plants. These results indicate that CsbZIP18 is a negative regulator of freezing tolerance via an ABA-dependent pathway.

Electronic Skin Wearable Sensors for Detecting Lumbar-Pelvic Movements.

BACKGROUND: A nanomaterial-based electronic-skin (E-Skin) wearable sensor has been successfully used for detecting and measuring body movements such as finger movement and foot pressure. The ultrathin and highly sensitive characteristics of E-Skin sensor make it a suitable alternative for continuously out-of-hospital lumbar-pelvic movement (LPM) monitoring. Monitoring these movements can help medical experts better understand individuals' low back pain experience. However, there is a lack of prior studies in this research area. Therefore, this paper explores the potential of E-Skin sensors to detect and measure the anatomical angles of lumbar-pelvic movements by building a linear relationship model to compare its performance to clinically validated inertial measurement unit (IMU)-based sensing system (ViMove). METHODS: The paper first presents a review and classification of existing wireless sensing technologies for monitoring of body movements, and then it describes a series of experiments performed with E-Skin sensors for detecting five standard LPMs including flexion, extension, pelvic tilt, lateral flexion, and rotation, and measure their anatomical angles. The outputs of both E-Skin and ViMove sensors were recorded during each experiment and further analysed to build the comparative models to evaluate the performance of detecting and measuring LPMs. RESULTS: E-Skin sensor outputs showed a persistently repeating pattern for each movement. Due to the ability to sense minor skin deformation by E-skin sensor, its reaction time in detecting lumbar-pelvic movement is quicker than ViMove by ~1 s. CONCLUSIONS: E-Skin sensors offer new capabilities for detecting and measuring lumbar-pelvic movements. They have lower cost compared to commercially available IMU-based systems and their non-invasive highly stretchable characteristic makes them more comfortable for long-term use. These features make them a suitable sensing technology for developing continuous, out-of-hospital real-time monitoring and management systems for individuals with low back pain.

Bionic Thermoelectric Response with Nanochannels.

Thermosensation, the ability to detect environmental temperature change, is one of most ancient and crucial processes for the survival of all living organisms. Mammals use temperature-sensitive transient receptor potential (thermoTRP) cation channels as thermometers to convert the temperature change into electrical signals that are finally received as action potentials by nerve endings. In this work, we report the bionic thermosensation by solid-state hybrid nanochannels based on the principle of thermally sensitive permselective ion transport. The hybrid nanochannels possess an asymmetric structure, consisting of ultrasmall silica nanochannels (∼2.3 nm in diameter, ∼100 nm in length) supported by large-sized track-etched poly(ethylene terephthalate) conical nanochannels. When the hybrid nanochannels are engineered to separate two electrolyte solutions, the temperature change in one solution can be directly converted into trans-nanochannel diffusion potential, akin to the natural thermosensation process. Two bionic modes, namely, in the absence and presence of a concentration gradient, were studied to imitate the natural thermosensation of thermoTRP ion channels and shark, respectively. In both cases, real-time thermoelectric response was captured with a fast relative response speed (electrical response time versus temperature change time) of higher than 98%, as well as excellent stability and reversibility. Moreover, the nanochannels are highly sensitive to thermal stimulus, showing a sensitivity of 0.71 mV/K comparable to the natural thermosensation. The experimental results coincide well with the theoretical relationship between electrical response and temperature change derived in terms of a quasi-steady-state ion transport model. Finite element simulations based on coupled Poisson-Nernst-Planck (PNP) and Einstein-Stokes equations were also performed, confirming that the sensitive thermoelectric response originates from the highly cationic selectivity of nanochannels.

Unraveling Mass and Electron Transfer Kinetics at Silica Nanochannel Membrane Modified Electrodes by Scanning Electrochemical Microscopy.

An in-depth understanding of kinetic processes convoluting mass and charge transfer at nanoporous membrane modified electrodes is crucial for developing high-performance electrochemical sensors. In this work, we propose a theoretical model to unravel mass (km) and electron transfer rate (kf) from the apparent electrochemical rate constant (kapp) at silica nanoporous membrane (SNM) modified indium tin oxide (ITO) electrodes (designated as SNM/ITO for simplicity). Using scanning electrochemical microscopy (SECM), the kapp of charged redox species was first determined at the SNM/ITO in the absence and presence of surfactant micelles inside SNM. On the basis of the theory, in the presence of micelles inside SNM, km equals zero for all charged probes (Ru(NH3)62+, Ru(CN)63-, and FcMeOH+), thus the SNM behaves as an insulating barrier and the overall electrode reactivity is dominated by the permeability of SNM. After excluding micelles from SNM, the km of Ru(CN)63-/4- is strongly dependent on the KCl concentration in the solution, decreasing from 0.23/0.15 mm s-1 to almost zero upon decreasing the KCl concentration from 1.0 to 0.01 M. In contrast, km increases from 1.33 to 2.4 mm s-1 for Ru(NH3)62+ and from 0.18 to 0.33 mm s-1 for FcMeOH+, which are comparable to the electron transfer rate at the underlying ITO electrode surface (0.8 and 0.35 mm s-1). In these cases, both mass and electron transfer processes are important in determining the overall redox activity of SNM/ITO electrodes. The methodology reported in this work can provide a quantitative way of unraveling these processes and their respective contributions.

Quantitative Assessment of Molecular Transport through Sub-3 nm Silica Nanochannels by Scanning Electrochemical Microscopy.

Scanning electrochemical microscopy (SECM) has been proved to be a powerful technique to study molecular transport across ionic channels in biomembranes and artificial nanoporous membranes. In this work SECM was used to study the dynamics of molecular transport across the ultrathin silica nanoporous membrane consisting of sub-3 nm diameter perpendicular channels. We focused on the quantitative assessment of permselectivity and permeability of the membrane and the effect of radial electrical double layer (EDL) on them. By SECM imaging, it was phenomenologically observed that the membrane with negatively charged surface exhibited permselectivity to anionic molecule, for instance hexacyanoruthenate(II) (Ru(CN)64-). And the permselective transport of Ru(CN)64- was obviously more favored at a higher concentration of KCl. Precise membrane permeability to Ru(CN)64- was quantitatively determined by overlapping experimental SECM approach curves with the ones generated by finite element simulations. The high permeability up to 35 µm s-1 was ascribed to the straight channel structure and ultrahigh channel density of 4 × 1012 cm-2. Moreover, the permeability was varied from 35 µm s-1 to 2.5 µm s-1 when decreasing the concentration of KCl from 1.0 to 0.01 M, corroborating the electrostatic origin of membrane permselectivity. On the other hand, the simulated concentration profiles at both sides of the membrane suggested that the molecular transport across the membrane was mainly driven by the large transmembrane concentration gradient while the tip-induced transport was relatively negligible. These results help to quantitatively understand the molecular transport selectivity and dynamics across nanoporous membranes and to rationally design artificial molecular sieving membranes.

Ionic Current Rectification by Laminated Bipolar Silica Isoporous Membrane.

Ionic current rectification (ICR) is one of interesting characteristics displayed by nanochannels with asymmetric geometry, ionic concentration or charge distribution, which has been utilized for the development of chemical sensors and biosensors. Herein we report the ICR phenomenon observed with ultrathin silica isoporous membrane (SIM), which was prepared by laminating two layers of SIM with opposite charges and different pore diameters, designated as bipolar SIM (bp-SIM). The negatively charged layer, called as n-SIM, was 86 nm-thick and consisted of channels with a diameter of 2-3 nm. The positively charged layer with a thickness of 59 nm, termed as p-SIM, was comprised of channels of 4.5-5.5 nm in diameter. They were primarily grown on the solid surface using the Stöber-solution and biphasic-stratification growth approaches, respectively, and then exfoliated to obtain perforated structures by the polymer-protected chemical etching and transfer method. The negative charges of n-SIM and positive ones of p-SIM were generated by the deprotonation of pristine surface silanol and postmodified ammonium groups, respectively. Neither n-SIM nor p-SIM alone displays the ICR characteristic, because of their symmetric structure and uniform charge distribution. When laminating two of them, an apparent ICR characteristic was observed for the bp-SIM with a typical diode-like current-voltage response. This behavior was rationalized to arise from the asymmetric charge distribution on two layers by finite element simulations. Considering the facile preparation and diverse surface functionalities, as well as its uniform and highly porous structure, the bp-SIM provides an attractive platform for designing ICR-based sensors.

In Vivo Monitoring of Oxygen in Rat Brain by Carbon Fiber Microelectrode Modified with Antifouling Nanoporous Membrane.

Oxygen (O2) is involved in many life activities, and its in vivo monitoring is of vital importance. In vivo electrochemistry with carbon fiber microelectrode (CFME) has been proven to be a suitable technique, but the surface fouling propensity poses a great challenge to its current stability and reliability. Herein we electro-grafted silica nanoporous membrane (SNM) consisting of uniform, closely packed, and vertically aligned nanochannels on the CFME surface, which was capable of protecting the surface effectively from biofouling and, meanwhile, preserving the permeability to O2. In comparison with a bare CFME, the SNM/CFME after implantation in the brain of a live rat maintained its analytical sensitivity to O2. Moreover, the implanted electrode could monitor O2 continuously under the in vivo condition, exhibiting an excellent current stability, as well as a fast response, up to 2 h. Further considering the high permeability, selectivity, and biocompatibility of SNM, we believe the modified CFME is a highly reliable sensor for long-term in vivo monitoring of O2, as well as other neurochemicals, with promise in physiological, ethological, and neurological studies.

Micro-RNA 205-5p is Involved in the Progression of Gastric Cancer and Targets Phosphatase and Tensin Homolog (PTEN) in SGC-7901 Human Gastric Cancer Cells.

BACKGROUND This study aimed to investigate the role of micro-RNA 205-5p (miR-205-5p) in the progression of gastric cancer, and the target of miR-205-5p in human gastric cancer cells in vitro. MATERIAL AND METHODS Expression of miR-205-5p and PTEN in gastric cancer tissue samples and adjacent normal gastric tissue from 35 patients was studied using immunohistochemistry and in situ hybridization. SGC-7901 human gastric cancer cells included a normal control (NC) group, a group transfected with empty vector (Vector), a group treated with miR-205-5p inhibitor (miR-inhibitor), and a group treated with miR-205-5p inhibitor and small interfering PTEN mRNA (miR-inhibitor+si-PTEN). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) measured miR-205-5p expression, cell proliferation was measured by MTT assay, cell apoptosis by flow cytometry, transwell and wound healing assays measured cell migration, and transmission electron microscopy (TEM) showed ultrastructural changes in SGC-7901 cells. PTEN, AKT and p-AKT protein expression were measured using Western blot. The correlation between miR-205-5p and PTEN was analyzed using a dual-luciferase reporter assay. RESULTS Increased expression of miR-205-5p and PTEN in gastric cancer tissues were correlated with tumor stage. In SGC-7901 cells, miR-205-5p mRNA expression in the miR-inhibitor and miR-inhibitor+si-PTEN groups was significantly lower than that in the NC group (P<0.001). In the miR-inhibitor group, cell proliferation was significantly decreased, and apoptosis was significantly increased (P<0.001). CONCLUSIONS In gastric cancer, increased expression of miR-205-5p was associated with tumor stage, and in SGC-7901 cells PTEN was a target gene for miR-205-5p.