RNF167-mediated ubiquitination of Tollip inhibits TNF-α-triggered NF-κB and MAPK activation.

Toll-interacting protein (Tollip) is a multifunctional regulator in cellular activities. However, whether its functions are subjected to post-translational modifications remains elusive. Here, we identified ubiquitination as a post-translational modification on Tollip. We found that Tollip interacted with ring finger protein 167 (RNF167) through its C-terminal coupling of ubiquitin to ER degradation (CUE) domain, and RNF167 functioned as the potential E3 ligase to attach K33-linked poly-ubiquitin chains to the Lys235 (K235) site of Tollip. Furthermore, we discovered Tollip could inhibit TNF-α-induced nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation, and substitution of Lys235 on Tollip to arginine failed to suppress TNF-α-NF-κB/MAPK (JNK) cascades, revealing the role of Tollip and its ubiquitination in NF-κB/MAPK pathways. Thus, our study reveals the novel biological function of Tollip and RNF167-dependent ubiquitination of Tollip in TNF-α signaling.

Fast Surface Oxygen Release Kinetics Accelerate Nanoparticle Exsolution in Perovskite Oxides.

Exsolution is a recent advancement for fabricating oxide-supported metal nanoparticle catalysts via phase precipitation out of a host oxide. A fundamental understanding and control of the exsolution kinetics are needed to engineer exsolved nanoparticles to obtain higher catalytic activity toward clean energy and fuel conversion. Since oxygen release via oxygen vacancy formation in the host oxide is behind oxide reduction and metal exsolution, we hypothesize that the kinetics of metal exsolution should depend on the kinetics of oxygen release, in addition to the kinetics of metal cation diffusion. Here, we probe the surface exsolution kinetics both experimentally and theoretically using thin-film perovskite SrTi0.65Fe0.35O3 (STF) as a model system. We quantitatively demonstrated that in this system the surface oxygen release governs the metal nanoparticle exsolution kinetics. As a result, by increasing the oxygen release rate in STF, either by reducing the sample thickness or by increasing the surface reactivity, one can effectively accelerate the Fe0 exsolution kinetics. Fast oxygen release kinetics in STF not only shortened the prereduction time prior to the exsolution onset, but also increased the total quantity of exsolved Fe0 over time, which agrees well with the predictions from our analytical kinetic modeling. The consistency between the results obtained from in situ experiments and analytical modeling provides a predictive capability for tailoring exsolution, and highlights the importance of engineering host oxide surface oxygen release kinetics in designing exsolved nanocatalysts.

The relationship between inflammatory markers, clinical characteristics, and cognitive performance in drug-naïve patients with schizophrenia.

Increasing evidence implicates that inflammatory factors do play a crucial role in the pathophysiology of schizophrenia. However, the association between inflammatory markers and different symptom dimensions and cognitive function of schizophrenia remains unclear. A total of 140 drug-naïve patients with schizophrenia and 69 healthy controls matched for age and gender were enrolled. Peripheral blood plasma concentrations of S-100 calcium-binding protein B (S100B), neutrophil gelatinase-associated lipocalin (NGAL), and interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assay (ELISA). Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS), and cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Compared with healthy controls, patients with schizophrenia had significantly worse cognitive function and lower levels of NGAL and IFN-γ (P < 0.001). In schizophrenia, plasma NGAL and IFN-γ levels negatively correlated with positive symptom scores (all P < 0.05). There was a positive correlation between plasma levels of NGAL and IFN-γ with visual learning, neurocognition, and MCCB total score (all P < 0.05). We found that NGAL levels (ß = 0.352, t = 5.553, 95% CI 0.228-0.477, P < 0.001) and negative symptoms subscale scores (ß = - 0.321, OR = 0.725, 95% CI 648-0.811, P < 0.001) were independently associated with the MCCB total score. Further, binary logistic regression analysis indicated that the concentrations of NGAL (ß = - 0.246, OR = 0.782, 95% CI 0.651-0.939, P = 0.008) were independently associated with the diagnosis of schizophrenia. There was a positive correlation between NGAL and IFN-γ levels and MCCB total score in schizophrenia. NGAL level was an independent protective factor for cognitive function and an independent risk factor for the diagnosis of schizophrenia.

Exsolution-Driven Surface Transformation in the Host Oxide.

Exsolution synthesizes self-assembled metal nanoparticle catalysts via phase precipitation. An overlooked aspect in this method thus far is how exsolution affects the host oxide surface chemistry and structure. Such information is critical as the oxide itself can also contribute to the overall catalytic activity. Combining X-ray and electron probes, we investigated the surface transformation of thin-film SrTi0.65Fe0.35O3 during Fe0 exsolution. We found that exsolution generates a highly Fe-deficient near-surface layer of about 2 nm thick. Moreover, the originally single-crystalline oxide near-surface region became partially polycrystalline after exsolution. Such drastic transformations at the surface of the oxide are important because the exsolution-induced nonstoichiometry and grain boundaries can alter the oxide ion transport and oxygen exchange kinetics and, hence, the catalytic activity toward water splitting or hydrogen oxidation reactions. These findings highlight the need to consider the exsolved oxide surface, in addition to the metal nanoparticles, in designing the exsolved nanocatalysts.

Peroxymonosulfate activation by nitrogen-doped herb residue biochar for the degradation of tetracycline.

Biochar is an environmentally friendly material with potential applications in water purification. In this study, herb residue nitrogen-doped biochar (N-BC) was fabricated and used to activate peroxymonosulfate (PMS). Characterization and density-functional theory (DFT) studies were conducted to explore the influence of nitrogen doping. Radical scavenging activity and electron paramagnetic resonance (EPR) spectroscopy revealed that non-radical singlet oxygen (1O2) is the main reactive oxidative species. Additionally, pyridinic-N was shown to play a pivotal role in the 1O2-dominated pathway. Three possible degradation pathways were proposed based on the identified degradation intermediates. Batch experiments confirmed that N-BC showed excellent catalytic performance and reusability. The best condition for tetracycline (TC) degradation efficiency (>99%) in 60 min was obtained when the dosage of N-BC was 1 g/L and the concentration of PMS was 5 mM. Furthermore, N-BC showed approximately 65.5% degradation efficiency within 4 cycles. Furthermore, the toxicity of degradation intermediates was examined using ECOSAR and T.E.S.T procedures. This study brings forth a feasible strategy to synthesize biochar. Furthermore, the proposed approach will facilitate the use of biochar in water purification.

Cultivated human intestinal fungus Candida metapsilosis M2006B attenuates colitis by secreting acyclic sesquiterpenoids as FXR agonists.

OBJECTIVE: Dysbiosis of the intestinal fungal community has been observed in inflammatory bowel disease (IBD); however, its potential role in IBD development and prevention remains unclear. Here, we explored the biological effects and molecular mechanisms of intestinal fungi isolated from human faeces on colitis in mice. DESIGN: Intestinal fungal strains with differential abundance in IBD were cultivated in human faeces and their effects on various mouse models of experimental colitis were evaluated. In addition, the bioactive metabolites secreted by the target fungus were accurately identified and their pharmacological effects and potential molecular targets were investigated in vitro and in vivo. RESULTS: The abundance of Candida spp was significantly higher in patients with IBD. After large-scale human intestinal fungal cultivation and functional analysis, Candida metapsilosis M2006B significantly attenuated various models of experimental colitis in wild-type, antibiotic-treated, germ-free, and IL10-/- mice by activating farnesoid X receptor (FXR). Among the seven acyclic sesquiterpenoids (F1-F7) identified as major secondary metabolites of M2006B, F4 and F5 attenuated colitis in mice by acting as novel FXR agonists. The therapeutic effects of M2006B and its metabolites on colitis via specific FXR activation were confirmed in Fxr -/- mice. CONCLUSION: This study revealed that C. metapsilosis M2006B significantly attenuated colitis in mice and identified two acyclic sesquiterpenoids (F4 and F5) as major active metabolites of M2006B. Notably, these metabolites were able to effectively treat experimental colitis by selectively activating FXR. Together, this study demonstrates that M2006B could be a beneficial intestinal fungus for treating and preventing IBD.

Anodic Shock-Triggered Exsolution of Metal Nanoparticles from Perovskite Oxide.

Nanoparticles decorated electrodes (NDEs) are useful in fuel cells, electrolyzers, water treatment, and chemical synthesis. Here, we show that by rapidly bringing a mixed ionic-electronic conductor outside its electrochemical stability window, one can achieve uniform dispersion of metallic nanoparticles inside its bulk and at the surface and improve its electrocatalytic performance when back under normal functional conditions. Surprisingly, this can happen under anodic as well as cathodic current/voltage shocks in an ABO3 perovskite oxide, La0.4Ca0.4Ti0.88Fe0.06Ni0.06O3-δ (LCTFN), across a wide range of H2/O2 gas environments at 800 °C. One possible mechanism for bulk Fe0/Ni0 precipitation under anodic shock condition is the incomplete oxygen oxidation (O2- → Oα-, 0 < α < 2), migration and escape of oxygen to interfaces, and "whiplash" transition-metal reduction due to low electronic conductivity. We show that both cathodic and anodic shocks can produce NDEs to enhance electrocatalytic performance, potentially improving the flexibility of this approach in practical devices.

A telerehabilitation programme in post-discharge COVID-19 patients (TERECO): a randomised controlled trial.

OBJECTIVES: To investigate superiority of a telerehabilitation programme for COVID-19 (TERECO) over no rehabilitation with regard to exercise capacity, lower limb muscle strength (LMS), pulmonary function, health-related quality of life (HRQOL) and dyspnoea. DESIGN: Parallel-group randomised controlled trial with 1:1 block randomisation. SETTING: Three major hospitals from Jiangsu and Hubei provinces, China. PARTICIPANTS: 120 formerly hospitalised COVID-19 survivors with remaining dyspnoea complaints were randomised with 61 allocated to control and 59 to TERECO. INTERVENTION: Unsupervised home-based 6-week exercise programme comprising breathing control and thoracic expansion, aerobic exercise and LMS exercise, delivered via smartphone, and remotely monitored with heart rate telemetry. OUTCOMES: Primary outcome was 6 min walking distance (6MWD) in metres. Secondary outcomes were squat time in seconds; pulmonary function assessed by spirometry; HRQOL measured with Short Form Health Survey-12 (SF-12) and mMRC-dyspnoea. Outcomes were assessed at 6 weeks (post-treatment) and 28 weeks (follow-up). RESULTS: Adjusted between-group difference in change in 6MWD was 65.45 m (95% CI 43.8 to 87.1; p<0.001) at post-treatment and 68.62 m (95% CI 46.39 to 90.85; p<0.001) at follow-up. Treatment effects for LMS were 20.12 s (95% CI 12.34 to 27.9; p<0.001) post-treatment and 22.23 s (95% CI 14.24 to 30.21; p<0.001) at follow-up. No group differences were found for lung function except post-treatment maximum voluntary ventilation. Increase in SF-12 physical component was greater in the TERECO group with treatment effects estimated as 3.79 (95% CI 1.24 to 6.35; p=0.004) at post-treatment and 2.69 (95% CI 0.06 to 5.32; p=0.045) at follow-up. CONCLUSIONS: This trial demonstrated superiority of TERECO over no rehabilitation for 6MWD, LMS, and physical HRQOL. TRIAL REGISTRATION NUMBER: ChiCTR2000031834.

Profiling Cystathionine ß/γ-Lyase in Complex Biosamples Using Novel Activatable Fluorogens.

Cystathionine lyase, the key enzyme in transsulfuration and reverse transsulfuration pathways, is involved in a wide array of physiological and pathophysiological processes in both mammals and nonmammals. Though the biological significance of the hydrogen sulfide/cystathionine lyase system in disease states is extensively discussed, the absence of molecular methods for direct monitoring of cystathionine lyase in complex biosamples renders the result unreliable and perplexing. Here, we present the first attempt at designing and developing effective activatable fluorescent probes for cystathionine lyase based on the naphthylamide scaffold. CBLP and CSEP were designed based on the catalytic preference of cystathionine ß-lyase (CBL) and cystathionine γ-lyase (CSE). Briefly, incorporation of cysteine/homocysteine as the recognition moiety and a carbamate ethyl sulfide group as a self-immolated linker proved to be an effective strategy for cystathionine lyase fluorescence reporting. CBLP exhibits high selectivity and sensitivity in vitro in semiquantifying CBL levels in roots of wild-type Arabidopsis thaliana and cbl mutants (cbl knockout: SALK_014740C, overexpressed: OE-CBL). Meanwhile, CSEP successfully detected CSE levels in HCC-LM3 cells, zebrafish models, and upregulated CSE in frozen section slides from the liver tissue of cecal ligation and puncture (CLP)-induced septic rats, which was also validated by Western blotting and immunohistochemical analysis. In summary, the practical design strategy facilitates profiling of cystathionine lyase activity in biological processes. It may pave the way for the development of accurate and efficient methods for the direct estimation of cystathionine lyase.

Recent progress in microwave-assisted preparations of 2D materials and catalysis applications.

On the urgency of metal-free catalysts, two-dimensional materials (2DMs) have caused extensive researches because of distinctive optical and electronic properties. In the last decade, microwave methods have emerged in rapid and effective preparations of 2DMs for catalysis. Microwave heating offers several advantages namely direct, fast, selective heating and uniform reaction temperature compared to conventional heating methods, thus bringing about high-yield and high-purity products in minutes or even seconds. This review summarizes recent advances in microwave-assisted preparations of 2DMs-based catalysts and their state-of-the-art catalytic performances. Microwave heating mechanisms are briefly introduced mainly focusing on microwave-matter interactions, which can guide the choice of precursors, liquid media, substrates, auxiliaries and experiment parameters during microwave radiation. We especially provide a detailed insight into various microwave-assisted procedures, classified as exfoliation, synthesis, doping, modification and construction towards different 2DMs nanomaterials. We also discuss how microwave affects the synthetic composition and microstructure of 2DMs-based catalysts, thereby deeply influencing their optical and electronic properties and the catalytic performances. Finally, advantages, challenges and prospects of microwave-assisted approaches for 2DMs nanomaterials are summarized to inspire the effective and large-scale fabrication of novel 2DMs-based catalysts.

The Effects of the Biceps Brachii and Brachioradialis on Elbow Flexor Muscle Strength and Spasticity in Stroke Patients.

Objective: Muscle weakness and spasticity are common consequences of stroke, leading to a decrease in physical activity. The effective implementation of precision rehabilitation requires detailed rehabilitation evaluation. We aimed to analyze the surface electromyography (sEMG) signal features of elbow flexor muscle (biceps brachii and brachioradialis) spasticity in maximum voluntary isometric contraction (MVIC) and fast passive extension (FPE) in stroke patients and to explore the main muscle groups that affect the active movement and spasticity of the elbow flexor muscles to provide an objective reference for optimizing stroke rehabilitation. Methods: Fifteen patients with elbow flexor spasticity after stroke were enrolled in this study. sEMG signals of the paretic and nonparetic elbow flexor muscles (biceps and brachioradialis) were detected during MVIC and FPE, and root mean square (RMS) values were calculated. The RMS values (mean and peak) of the biceps and brachioradialis were compared between the paretic and nonparetic sides. Additionally, the correlation between the manual muscle test (MMT) score and the RMS values (mean and peak) of the paretic elbow flexors during MVIC was analyzed, and the correlation between the modified Ashworth scale (MAS) score and the RMS values (mean and peak) of the paretic elbow flexors during FPE was analyzed. Results: During MVIC exercise, the RMS values (mean and peak) of the biceps and brachioradialis on the paretic side were significantly lower than those on the nonparetic side (p < 0.01), and the RMS values (mean and peak) of the bilateral biceps were significantly higher than those of the brachioradialis (p < 0.01). The MMT score was positively correlated with the mean and peak RMS values of the paretic biceps and brachioradialis (r = 0.89, r = 0.91, r = 0.82, r = 0.85; p < 0.001). During FPE exercise, the RMS values (mean and peak) of the biceps and brachioradialis on the paretic side were significantly higher than those on the nonparetic side (p < 0.01), and the RMS values (mean and peak) of the brachioradialis on the paretic side were significantly higher than those of the biceps (p < 0.01). TheMAS score was positively correlated with the mean RMS of the paretic biceps and brachioradialis (r = 0.62, p = 0.021; r = 0.74, p = 0.004), and the MAS score was positively correlated with the peak RMS of the paretic brachioradialis (r = 0.59, p = 0.029) but had no significant correlation with the peak RMS of the paretic biceps (r = 0.49, p > 0.05). Conclusions: The results confirm that the biceps is a vital muscle in active elbow flexion and that the brachioradialis plays an important role in elbow flexor spasticity, suggesting that the biceps should be the focus of muscle strength training of the elbow flexors and that the role of the brachioradialis should not be ignored in the treatment of elbow flexor spasticity. This study also confirmed the application value of sEMG in the objective assessment of individual muscle strength and spasticity in stroke patients.

Rational Design of a Two-Photon Fluorescent Probe for Human Cytochrome†P450 3A and the Visualization of Mechanism-Based Inactivation.

Mechanism-based inactivation (MBI) can mediate adverse reactions and hepatotoxicity from drugs, which is a result of their conversion into highly reactive metabolites catalyzed by enzymes such as cytochrome P450 3A (CYP3A). In the present research, we optimized the key interaction domain of the fluorophore with the target protein to develop a two-photon fluorescent probe for CYP3A that is involved in the metabolism of more than half of all clinical drugs. The developed BN-1 probe exhibited appropriate selectivity and sensitivity for the semi-quantitative detection and imaging of endogenous CYP3A activity in various living systems, thereby providing a high-throughput screening system enabling evaluation of MBI-associated hepatotoxicity by CYP3A. Using BN-1 as a fluorescent molecular tool facilitates the efficient discovery and characterization of CYP3A-induced MBI in natural systems.

Bi-directional tuning of thermal transport in SrCoOx with electrochemically induced phase transitions.

Unlike the wide-ranging dynamic control of electrical conductivity, there does not exist an analogous ability to tune thermal conductivity by means of electric potential. The traditional picture assumes that atoms inserted into a material's lattice act purely as a source of scattering for thermal carriers, which can only reduce thermal conductivity. In contrast, here we show that the electrochemical control of oxygen and proton concentration in an oxide provides a new ability to bi-directionally control thermal conductivity. On electrochemically oxygenating the brownmillerite SrCoO2.5 to the perovskite SrCoO3-δ, the thermal conductivity increases by a factor of 2.5, whereas protonating it to form hydrogenated SrCoO2.5 effectively reduces the thermal conductivity by a factor of four. This bi-directional tuning of thermal conductivity across a nearly 10 ± 4-fold range at room temperature is achieved by using ionic liquid gating to trigger the 'tri-state' phase transitions in a single device. We elucidated the effects of these anionic and cationic species, and the resultant changes in lattice constants and lattice symmetry on thermal conductivity by combining chemical and structural information from X-ray absorption spectroscopy with thermoreflectance thermal conductivity measurements and ab initio calculations. This ability to control multiple ion types, multiple phase transitions and electronic conductivity that spans metallic through to insulating behaviour in oxides by electrical means provides a new framework for tuning thermal transport over a wide range.

Overexpression of SmZIP plays important roles in Cd accumulation and translocation, subcellular distribution, and chemical forms in transgenic tobacco under Cd stress.

Plant ZIP genes represent an important transporter family and may be involved in cadmium (Cd) accumulation and Cd resistance. In order to explore the function of SmZIP isolated from Salix matsudana, the roles of SmZIP in Cd tolerance, uptake, translocation, and distribution were determined in the present investigation. The transgenic SmZIP tobacco was found to respond to external Cd stress differently from WT tobacco by exhibiting a higher growth rate and more vigorous phenotype. The overexpression of SmZIP in tobacco resulted in the reduction of Cd stress-induced phytotoxic effects. Compared to WT tobacco, the Cd content of the root, stem, and leaf in the transgenic tobacco increased, and the zinc, iron, copper, and manganese contents also increased. The assimilation factor, translocation factor and bioconcentration factor of Cd were improved. The scanning electron microscopy and energy dispersive X-ray analysis results of the root maturation zone exposed to Cd for 24 h showed that Cd was transferred through the root epidermis, cortex, and vascular cylinder and migrated to the aboveground parts via the vascular cylinder, resulting in the transgenic tobacco accumulating more Cd than the WT plants. Based on the transverse section of the leaf main vein and leaf blade, Cd was transported through the vascular tissues to the leaves and accumulated more greatly in the leaf epidermis, but less in the leaf mesophyll cells, following the overexpression of SmZIP to reduce the photosynthetic toxicity. The overexpression of SmZIP resulted in the redistribution of Cd at the subcellular level, a decrease in the percentage of Cd in the cell wall, and an increase of the Cd in the soluble fraction in both the roots and leaves. It also changed the percentage composition of different Cd chemical forms by elevating the proportion of Cd extracted using 2% HAc and 0.6 mol/L HCl, but lowering that of the Cd extracted using 1 mol/L NaCl in both the leaves and roots under 10 and 100 µmol/L Cd stress for 28 d. The results implied that SmZIP played important roles in advancing Cd uptake, accumulation, and translocation, as well as in enhancing Cd resistance by altering the Cd subcellular distribution and chemical forms in the transgenic tobacco. The study will be useful for future phytoremediation applications to clean up Cd-contaminated soil.

Interference with lncRNA NEAT1 promotes the proliferation, migration, and invasion of trophoblasts by upregulating miR-411-5p and inhibiting PTEN expression.

Background: Preeclampsia (PE) is an idiopathic hypertensive disorder of pregnancy, which is related to abnormal placental villi development. Our previous study has found that lncRNA NEAT1 promotes apoptosis of trophoblasts, but the role of NEAT1 in proliferation, migration, and invasion is still unclear. This study explores the role of NEAT1 in proliferation, migration, and invasion of trophoblasts.Methods: NEAT1 and miR-411-5p levels were detected by quantitative real-time PCR. Colony formation assay detected cell proliferation and transwell assay detected cell migration and invasion. Dual-luciferase reporter assay detected the binding between NEAT1 and miR-411-5p as well as the binding between miR-411-5p and PTEN. RNA pull-down assay detected the combination between NEAT1 and miR-411-5p.Result: NEAT1 was increased and miR-411-5p was reduced in PE patients and human trophoblasts (HTR8/SVneo cells) that were induced with H2O2. Interference with NEAT1 promoted cell proliferation, migration, and invasion, and the miR-411-5p inhibitor reversed the effect of siRNA-NEAT1. The expression of PTEN was promoted in PE patients and HTR8/SVneo cells that were induced with H2O2, while the miR-411-5p mimic inhibited PTEN expression, and the plasmid-mediated PTEN overexpression reversed the effect of the miR-411-5p mimic. Besides, under H2O2 induction, the miR-411-5p mimic promoted cell proliferation, migration, and invasion, and the plasmid-mediated PTEN overexpression reversed the effect of the miR-411-5p mimic.Conclusion: Interference with lncRNA NEAT1 promoted the proliferation, migration, and invasion of trophoblasts and alleviated the development of PE, which was partly mediated by upregulating miR-411-5p and inhibiting PTEN expression.

Simultaneous measurement of aqueous redox-sensitive elements and their species across the soil-water interface.

The redox-sensitive elements, such as iron, manganese, sulfur, phosphorus, and arsenic, shift their speciation every millimeter (mm) across the soil-water interface in the flooded soil environments. Monitoring of element speciation at this high-resolution (HR) within the SWI is still difficult. The key challenge lies in obtaining sufficient porewater samples at specific locations along the soil gradient for downstream analysis. Here with an optimized inductively coupled plasma mass spectrometry (ICP-MS) method and a HR porewater sampler, we demonstrate mm-scale element profiles mapping across the SWI in paddy soils. High-concentrations of iron and manganese (> 10 mg/L) were measured by ICP-MS in an extended dynamic range mode to avoid signal overflow. The iron profile along the SWI generated by the ICP-MS method showed no significant difference (p < 0.05) compared to that measured independently using a colorimetric method. Furthermore, four arsenic (arsenite, arsenate, monomethylarsonic and dimethylarsinic acid), two phosphorus (phosphite and phosphate) and two sulfur (sulfide and sulfate) species were separated in 10 min by ion chromatography -ICP-MS with the NH4HCO3 mobile phase. We verified the technique using paddy soils collected from the field, and present the mm-scale profiles of iron, manganese, and arsenic, phosphorus, sulfur species (relative standard deviation < 8%). The technique developed in this study will significantly promote the measurement throughput in limited samples (e.g. 100 µL) collected by HR samplers, which would greatly facilitate redox-sensitive elements biogeochemical cycling in saturated soils.

A novel homozygous mutation p.E88K in maternal SLC30A2 gene as a cause of transient neonatal zinc deficiency.

The SLC30A2 gene encodes zinc transporter ZnT2, which is indispensable for the transport of zinc into the breast milk in the mammary gland. Transient neonatal zinc deficiency (TNZD) is caused by a mutation in the maternal SLC30A2 gene and has a clinical presentation similar to that of acrodermatitis enteropathica (AE). We described the case of a Chinese infant who presented with AE-like lesions 10 days after birth. Sanger sequencing of the AE-causing gene SLC39A4 revealed no mutations in genomic DNA from the infant, excluding the possibility of AE. Detection of the mother's breast milk showed a significantly lower zinc level. Thus, SLC30A2 sequencing was performed on her genomic DNA and a previously unreported homozygous c.262G > A (p.E88K) mutation was disclosed. Functional analysis suggested the novel mutation could lead to a strong disruption of zinc secretion, which indicated a complete loss of function in the ZnT2 protein. We finally diagnosed the infant with TNZD. To the best of our knowledge, this is the first case of TNZD caused by a homozygous mutation in the maternal SLC30A2 gene. Compared to the heterozygous condition, a homozygous mutation seems to result in a more significant decrease in zinc secretion and a more rapid onset of TNZD.

Origin and evolution of emerging Liao ning Virus (genus Seadornavirus, family Reoviridae).

BACKGROUND: Liao ning virus (LNV) is a member of the genus Seadornavirus, family Reoviridae and has been isolated from kinds of vectors in Asia and Australia. However, there are no systematic studies describe the molecular genetic evolution and migration of LNVs. With the development of bioinformatics, viral genetic data combining the information of virus isolation time and locations could be integrated to infer the virus evolution and spread in nature. METHODS: Here, a phylogenetic and phylogeographic analysis using Bayesian Markov chain Monte Carlo simulations was conducted on the LNVs isolated from a variety of vectors during 1990-2014 to identify the evolution and migration patterns of LNVs. RESULTS: The results demonstrated that the LNV could be divided into 3 genotypes, of which genotype 1 mainly composed of LNVs isolated from Australia during 1990 to 2014 and the original LNV strain (LNV-NE97-31) isolated from Liaoning province in northern China in 1997, genotype 2 comprised of the isolates all from Xinjiang province in western China and genotype 3 consisted the isolates from Qinghai and Shanxi province of central China. LNVs emerged about 272 years ago and gradually evolved into three lineages in the order genotype 1, genotype 2 and genotype 3. Following phylogeographic analysis, it shows genotype 1 LNVs transmitted from Australia (113°E-153°E,10°S-42°S) to Liaoning province (118°E-125°E,38°N-43°N) in Northeast Asian continent then further spread across the central part of China to western China (75°E-95°E,35°N-50°N). CONCLUSION: LNVs were initially isolated from Liaoning province of China in the Northeast Asia, however, the present study revealed that LNVs were first appeared in Australia in the South Pacific region and transmitted to mainland China then rapidly spread across China and evolved three different genotypes. The above results suggested that LNV had the characteristics of long-distance transmission and there were great genetic diversity existed in the LNV population. Notably, current information of 80 strains of LNVs are limited. It is of great importance to strengthen the surveillance of LNVs to explore its real origin in nature and monitoring of the LNVs' population variation and maintain vigilance to avoid LNV breaking through the species barrier and further clarify its relationship to human and animal infection.