The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity.

The RNA modification N6-methyladenosine (m6A) has critical roles in many biological processes1,2. However, the function of m6A in the early phase of mammalian development remains poorly understood. Here we show that the m6A reader YT521-B homology-domain-containing protein 1 (YTHDC1) is required for the maintenance of mouse embryonic stem (ES) cells in an m6A-dependent manner, and that its deletion initiates cellular reprogramming to a 2C-like state. Mechanistically, YTHDC1 binds to the transcripts of retrotransposons (such as intracisternal A particles, ERVK and LINE1) in mouse ES cells and its depletion results in the reactivation of these silenced retrotransposons, accompanied by a global decrease in SETDB1-mediated trimethylation at lysine 9 of histone H3 (H3K9me3). We further demonstrate that YTHDC1 and its target m6A RNAs act upstream of SETDB1 to repress retrotransposons and Dux, the master inducer of the two-cell stage (2C)-like program. This study reveals an essential role for m6A RNA and YTHDC1 in chromatin modification and retrotransposon repression.

Resolving Cell Fate Decisions during Somatic Cell Reprogramming by Single-Cell RNA-Seq.

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs), which is a highly heterogeneous process. Here we report the cell fate continuum during somatic cell reprogramming at single-cell resolution. We first develop SOT to analyze cell fate continuum from Oct4/Sox2/Klf4- or OSK-mediated reprogramming and show that cells bifurcate into two categories, reprogramming potential (RP) or non-reprogramming (NR). We further show that Klf4 contributes to Cd34+/Fxyd5+/Psca+ keratinocyte-like NR fate and that IFN-γ impedes the final transition to chimera-competent pluripotency along the RP cells. We analyze more than 150,000 single cells from both OSK and chemical reprograming and identify additional NR/RP bifurcation points. Our work reveals a generic bifurcation model for cell fate decisions during somatic cell reprogramming that may be applicable to other systems and inspire further improvements for reprogramming.

Field-dependent deep learning enables high-throughput whole-cell 3D super-resolution imaging.

Single-molecule localization microscopy in a typical wide-field setup has been widely used for investigating subcellular structures with super resolution; however, field-dependent aberrations restrict the field of view (FOV) to only tens of micrometers. Here, we present a deep-learning method for precise localization of spatially variant point emitters (FD-DeepLoc) over a large FOV covering the full chip of a modern sCMOS camera. Using a graphic processing unit-based vectorial point spread function (PSF) fitter, we can fast and accurately model the spatially variant PSF of a high numerical aperture objective in the entire FOV. Combined with deformable mirror-based optimal PSF engineering, we demonstrate high-accuracy three-dimensional single-molecule localization microscopy over a volume of ~180 × 180 × 5 µm3, allowing us to image mitochondria and nuclear pore complexes in entire cells in a single imaging cycle without hardware scanning; a 100-fold increase in throughput compared to the state of the art.

Uncovering the predictive pathways of lithium and sodium interchange in layered oxides.

Ion exchange is a powerful method to access metastable materials with advanced functionalities for energy storage applications. However, high concentrations and unfavourably large excesses of lithium are always used for synthesizing lithium cathodes from parent sodium material, and the reaction pathways remain elusive. Here, using layered oxides as model materials, we demonstrate that vacancy level and its corresponding lithium preference are critical in determining the accessible and inaccessible ion exchange pathways. Taking advantage of the strong lithium preference at the right vacancy level, we establish predictive compositional and structural evolution at extremely dilute and low excess lithium based on the phase equilibrium between Li0.94CoO2 and Na0.48CoO2. Such phase separation behaviour is general in both surface reaction-limited and diffusion-limited exchange conditions and is accomplished with the charge redistribution on transition metals. Guided by this understanding, we demonstrate the synthesis of NayCoO2 from the parent LixCoO2 and the synthesis of Li0.94CoO2 from NayCoO2 at 1-1,000 Li/Na (molar ratio) with an electrochemical assisted ion exchange method by mitigating the kinetic barriers. Our study opens new opportunities for ion exchange in predictive synthesis and separation applications.

Incorporation of Finasteride-Loaded Microspheres into Personalized Microneedle for Sustained Transdermal Delivery.

Although finasteride (FNS) tablets are considered the most effective drug for the treatment of androgenetic alopecia (AGA), their clinical applications are limited due to the associated side effects including decreased libido, breast enlargement, and liver dysfunction. In this study, we have developed a personalized microneedle (PMN) with a double-layer structure that incorporates FNS-loaded microspheres (MPs) to accommodate irregular skin surfaces. This design enables the sustained release of FNS, thereby reducing potential side effects. The needle body was synthesized with high-strength hyaluronic acid (HA) as the base material substrate. The backing layer utilized methacrylate gelatin (GelMA) with specific toughness, enabling PMN to penetrate the skin while adapting to various skin environments. The length of PMN needles (10 × 10) was approximately 600 µm, with the bottom of the needles measuring about 330 µm × 330 µm. The distance between adjacent tips was around 600 µm, allowing the drug to penetrate the stratum corneum of the skin. The results of the drug release investigation indicated the sustained and regulated release of FNS from PMN, as compared to that of pure FNS and FNS-MPs. Further, the cytotoxicity assay demonstrates that PMS displays good cytocompatibility. Altogether, this mode of administration has immense potential for the development of delivery of other drugs, as well as in the medical field.

pBACode: a random-barcode-based high-throughput approach for BAC paired-end sequencing and physical clone mapping.

Applications that use Bacterial Artificial Chromosome (BAC) libraries often require paired-end sequences and knowledge of the physical location of each clone in plates. To facilitate obtaining this information in high-throughput, we generated pBACode vectors: a pool of BAC cloning vectors, each with a pair of random barcodes flanking its cloning site. In a pBACode BAC library, the BAC ends and their linked barcodes can be sequenced in bulk. Barcode pairs are determined by sequencing the empty pBACode vectors, which allows BAC ends to be paired according to their barcodes. For physical clone mapping, the barcodes are used as unique markers for their linked genomic sequence. After multi-dimensional pooling of BAC clones, the barcodes are sequenced and deconvoluted to locate each clone. We generated a pBACode library of 94,464 clones for the flounder Paralichthys olivaceus and obtained paired-end sequence from 95.4% of the clones. Incorporating BAC paired-ends into the genome preassembly improved its continuity by over 10-fold. Furthermore, we were able to use the barcodes to map the physical locations of each clone in just 50 pools, with up to 11 808 clones per pool. Our physical clone mapping located 90.2% of BAC clones, enabling targeted characterization of chromosomal rearrangements.

Photocatalytic oxidation of trace carbamazepine in aqueous solution by visible-light-driven Znln2S4: Performance and mechanism.

In this work, visible-light-driven Znln2S4 photocatalyst (band gap 1.98 eV, absorption wavelength 300-600 nm) was synthesized by a facile hydrothermal method for photocatalytic degradation of trace pharmaceutical carbamazepine (CBZ) in aqueous solution, and characterized by UV-Vis diffusive reflectance spectroscopy, BET, SEM and XRD, respectively. It demonstrated that a complete degradation of CBZ was achieved with an optimal Znln2S4 dosage of 30 mg/L under a 100 W iodine-gallium lamp irradiation of 20 min, which afforded the reaction rate constant and half-life being respectively 10.44 times higher and 1/8 less than that obtained by a direct photolysis without Znln2S4 photocatalyst. A negligible influence of initial solution pH on photocatalytic degradation of CBZ was confirmed under the given pH range of 5.0-9.0. The degradation efficiency of CBZ was slightly decreased from 91% to 84% after five consecutive cycles. Hydroxy radical (·OH) plays an important role in CBZ degradation accompanying a synergistic effect of photogenerated hole (h+) and O2- active species during reaction. Further, 44 intermediates were detected by LCMS-IT-TOF technique and tentative degrading pathways were proposed on the basis of the experimental results.

The role of silver and gold nanoparticles in enhancing luminescence of europium complexes.

The influence of 12 nm spherical silver nanoparticles (AgNPs) and 20 nm spherical gold nanoparticles (AuNPs) on the luminescence of europium complex Eu(TTFA)3 were studied. When 350 nm is chosen as the incident light, the maximum enhancement factor of the complexes mixed with AgNPs is about 2.5 at the wavelength of 612 nm. Besides the enhancement of the localized field, the overlap between the localized surface plasmon resonance spectra of nanoparticles and the absorption band of fluorescent molecules is another important factor for excitation field enhancement. By means of the quasi-static approximation theory, the distribution of the electric field around a single spherical metallic nanopaticle illuminated by plane wave was calculated. The simulation results show that the field enhancement effect is more obvious when the incident light is close to the resonance of the metallic nanoparticle, which could be demonstrated by our following experimental results. The distribution of the electric field under the same conditions was also simulated through the COMSOL software. The results are consistent with those of the quasi-static approximation theory.

Excess sludge-based biochar loaded with manganese enhances catalytic ozonation efficiency for landfill leachate treatment.

This study developed an efficient and stable landfill leachate treatment process, which was based on the combination of biochar catalytic ozonation and activated sludge technology for intensive treatment of landfill leachate, aiming to achieve the standard discharge of leachate. The focus is to investigate the effect of manganese loading on the physicochemical properties of biochar and the mechanism of its catalytic ozonation. It was found that more surface functional groups (CO, Mn-O, etc.) and defects (ID/IG = 1.27) were exposed via the change of original carbon structure by loading Mn, which is conducive to the generation of lattice oxygen. Meanwhile, generating different valence states of Mn metal can improve the redox properties and electron migration rate, and encourage the production of reactive oxygen species (ROS) during the reaction process and enhance the catalytic efficiency. The synergistic action of microorganisms, especially denitrifying bacteria, was found to play a key role in the degradation of nitrogenous pollutants during the activated sludge process. The concentration of NH+4-N was reduced from the initial 1087.03 ± 9.56 mg/L to 9.05 ± 1.91 mg/L, while COD was reduced from 2290 ± 14.14 mg/L to 86.5 ± 2.12 mg/L, with corresponding removal rates of 99.17% and 99.20%, respectively. This method offers high efficiency and stability, achieving discharge standards for leachate (GB16889-2008). The synergy between Mn-loaded biochar and microorganisms in the activated sludge is key to effective treatment. This study offers a new approach to solving the challenge of waste leachate treatment.

Acid etching post-treatment enhanced fungal sterilization performance of copper-manganese-cerium oxide in liquid and aerosol: Materials and molecular biological mechanisms.

Bioaerosol is one of the main ways to spread respiratory infectious diseases. In order to further improve the sterilization efficiency of copper-manganese-cerium oxide (CuMnCeOx), the post-treatment method based on acid etching was adopted. The results showed that sterilization efficiency of the treated CuMnCeOx could reach 99% in aerosol with space velocity of 1400 h-1. L(+)-ascorbic acid successfully promoted the formation of Cu+, oxygen vacancies and the generation of reactive oxygen species (ROS) on the surface of the treated CuMnCeOx. During sterilization in liquid system, the transcriptome identified 316 differentially expressed genes, including 270 up-regulated genes and 46 down-regulated genes. Differentially expressed genes were significantly enriched in cell wall (GO:0005618) and external encapsulating structure (GO:0030312). Up-regulated genes were shown in regulation of reactive oxygen species biosynthetic processes (GO:1903409, GO:1903426, GO:1903428) and positive regulation all of reactive oxygen species metabolic process (GO:2000379), indicating that ROS induced cell death by destroying cell wall.

Population genetics reveals new introgression in the nucleus herd of min pigs.

OBJECTIVE: Min pigs are a unique genetic resource among local pig breeds in China. They have more excellent characteristics in cold and stress resistance, good meat quality, and a high reproductive rate. However, the genetic structure and driving factors remain unclear in the nucleus herd. In this study, the genetic diversity of Min pigs was studied to reveal the formation mechanism of its unique genetic structure. We hope to protect and develop the genetic resources of Min pigs. METHODS: We analyzed different types of genes to identify the genetic structure and gene introgression pattern of Min pigs. The nuclear DNA dataset includes information on 21 microsatellite loci and 6 Y-chromosome genes, and the mitochondrial D-loop gene is selected to represent maternal lineages. The above genes are all from the nucleus herd of Min pigs. RESULTS: The results of genetic structure identification and analysis of potential exogenous gene introgression patterns indicate that the nucleus herd of Min pigs maintains a high level of genetic diversity (polymorphism information content = 0.713, expected heterozygosity = 0.662, observed heterozygosity = 0.612). Compared with other Asian pig breeds, the formation of Min pig breeds is more special. Gene introgression from European pig breeds to Min pigs has occurred, which is characterized by complete introgression of paternal genes and incomplete introgression of maternal genes. CONCLUSION: Gene introgression caused by cross-breeding is not the main factor leading to the formation of the current genetic structure of Min pigs, but this process has increased the level of genetic diversity in the nucleus herd. Compared with the influence of gene introgression, our research suggest that artificial selection and environmental adaptive evolution make Min pigs form unique genetic characteristics.

The activation of peroxymonosulfate by biochar derived from anaerobic and aerobic iron-containing excess sludge.

The excess sludge from municipal sewage treatment plants is rich in Fe (III) due to chemical dephosphorization. The activation of peroxymonosulfate (PMS) by biochar derived from anaerobic and aerobic iron-containing excess sludge was studied systematically in this research. Fe (III)-containing excess sludge was cultured in an anaerobic environment for conversion of partial Fe (III) to Fe (II), which was further carbonized to prepare biochar labeled AnSx@Fe. Meanwhile, aerobic sludge with different Fe (III) content was directly carbonized to produce biochar labeled AeS@Fe. For biochar (AnS20@Fe-15%) prepared from 15% Fe(III)-containing anaerobic cultured 20 days sludge, the relative contents of Fe (III) and Fe (II) were 21.26% and 78.74%, which were 31.03% and 68.97% for biochar (AeS@Fe-10%) prepared from 10% Fe (III)-containing aerobic sludge. Fe (III) can be reduced to Fe (II) by both anaerobic culture and carbonization. Their removal rates of tetracycline (TC) through 60 min PMS activation were 97% and 98%, with TOC (Total organic carbon) removal of 61.8% and 53.4% respectively. The reactive species including sulfate radical [Formula: see text], hydroxyl radical (·OH) and singlet oxygen (1O2) were produced during PMS activation. After O2-aeration treatment of both AeS@Fe and AnSx@Fe, the relative content of Fe (II) was decreased and group C = O was disappeared, which resulted in reduction of [Formula: see text], ·OH and 1O2. The generation of [Formula: see text] and ·OH was dominated by the Fe (II) activation and the 1O2 generation was originated from graphite type N and C = O. Direct carbonization of aerobic and anaerobic sludge is a feasible method to produce biochar for PMS activation.

The efficiency and mechanism of excess sludge-based biochar catalyst in catalytic ozonation of landfill leachate.

In this study, biochar was produced based on dehydrated excess sludge from the municipal wastewater treatment plant, which was used for catalytic ozonation of pollutants derived from landfill leachate. The necessary catalytic sites in the structure of biochar were originated from the inorganic metals and organic matters in the sludge, which included a large number of functional groups (e.g., C-C, CO, etc.), adsorbed oxygen (Oads accounted for 44.82%) and electron defects (ID/IG=1.01). These active sites could promote the generation of reactive oxygen species (ROS) (e.g., ·OH,·O2-, etc.). The synergistic interaction between the microorganisms in the activated sludge also facilitated the removal rates of pollutants. Proteobacteria, Bacteroidetes, and Deinococcu-Thermus were crucial in the bioreactor. In 16 days of reaction, the removal ratios of NH+4-N and COD were 98.95 ± 0.11% and 90.89 ± 0.47%, respectively. This study not only explains the mechanism of catalytic ozonation of biochar, but also provides a new way of the practical treatment of landfill leachate.

Prospects for humic acids treatment and recovery in wastewater: A review.

Clean water shortages require the reuse of wastewater. The presence of organic substances such as humic acids in wastewater makes the water treatment process more difficult. Humic acids can significantly affect the removal of heavy metals and other such toxins. Humic acids is formed by the decomposition and transformation of animal and plant remains by microorganisms, and naturally exists in soil and water. It is necessary to degrade and remove humic acids from wastewater. As it seriously human health, effective technologies for removing humic acids from wastewater have attracted great interest over the past decades. This study compared existing techniques for removing humic acids from wastewater, as well as their limitations. Physicochemical treatments including filtration and oxidation are basic and key approaches to removing humic acids. Biological treatments including enzyme and fungi-mediated humic acids degradation are economically feasible but require some scalability. In conclusion, the integrated treatment processes are more significant options for the effective removal of humic acids from wastewater. In addition, humic acids have rich utilization values. It can improve the soil, increase crop yields, and promote the removal of pollutants.

Novel biotin-linked amphiphilic calix[4]arene-based supramolecular micelles as doxorubicin carriers for boosted anticancer activity.

Supramolecular carrier-mediated chemotherapy is a highly attractive strategy for targeted drug delivery. In this study, four novel biotin-linked calix[4]arenes BPCA1-BPCA4 have been rationally designed to construct nano-complex with doxorubicin. The in vitro and in vivo assessments reveal that BPCA4-DOX with excellent stability are capable of affording significantly superior anti-tumor activity and lower side effects.

Photoelectrocatalytic mechanism of PEDOT modified filtration membrane.

The generation of free radicals is the key to the photocatalytic efficiency. In this study, the degradation mechanism of photoelectrocatalysis (PEC) membrane could be adequately explained by exploring the generation pathway of different free radicals. The PEC membrane was prepared by gas phase polymerization of poly (3, 4-ethylene dioxythiophene) (PEDOT) on non-woven fabric, industrial filter cloth, ceramic membrane and polyvinylidene fluoride (PVDF) membrane, respectively. Three-dimensional fluorescence test showed that the optimal degradation of mixed or monomer contamination (bovine serum protein, sodium humate, and sodium alginate) was achieved by modified ceramic membrane under PEC condition. As for self-cleaning experiment, the membrane resistance decreased 65.7% when the reaction conditions changed from dark to PEC for 30 min. Combined with the characterization results, PEDOT as photocapacitance extended electron lifetime and promoted free radical generation. This system was mainly dependent on superoxide free radicals (0.01 mmol/L) and singlet oxygen (0.10 mmol/L), which came from energy and electron transfer. Oxygen vacancy could adsorb oxygen to produce superoxide radicals, which was further oxidized to singlet oxygen. In addition, the π-electron conjugated system of PEDOT accelerated the hole transfer and the separation of electrons and holes. Also, this study provided a new view of reactive oxygen species generation mechanism from PEDOT modified membrane.

The effect of activated sludge treatment and catalytic ozonation on high concentration of ammonia nitrogen removal from landfill leachate.

This study adopted the combination of activated sludge treatment and catalytic ozonation technology to efficiently remove the high concentration of ammonia nitrogen from landfill leachate. Through optimizing the parameters continuously, the COD, NH4+-N, UV254 and colority respectively descended to 417.75 ± 6.72 mg/L, 9.77 mg/L, 1.98 ± 0.04 and 40 times, and 3D fluorescence also reduced significantly within 14 days. Target genes of AOB-amoA, nxrA, napA, nirS and nosZ analysis indicated that ammonia-oxidizing bacteria, nitrated bacteria, and denitrifying bacteria played a key role on nitrogen removal, aerobic denitrifying bacteria was dominated especially. The nitrogen removal process was as follows: catalytic ozonation converted nitrogen-containing organic matter into NH4+-N, then NH4+-N was converted into NO2--N and NO3--N with the action of ammonia oxidation, nitrification and catalytic ozonation. Finally, the denitrification microorganisms transformed NO3--N or NO2--N to N2. Therefore, this coupled process realized the nitrogen removal effectively from landfill leachate.

Optical properties of silver nanoprisms and their influences on fluorescence of europium complex.

The optical properties of truncated triangular silver nanoprisms and their influences on the fluorescence of europium complex Eu(TTFA)(3) were investigated in theory and experiment separately. In theory, we found that the fluorescence of Eu ions would be greatly enhanced by these nanoprisms, the enhancement factor of the fluorescence depended on the concentrations of nanoprisms. They were verified in the experiment. The influence of silver nanoprisms on the radiative and nonradiative decay rates of Eu ions were also deduced, and found that the silver nanoprisms greatly reduced the energy loss caused by the nonradiative decay.

Ozone direct oxidation pretreatment and catalytic oxidation post-treatment coupled with ABMBR for landfill leachate treatment.

In order to treat the high concentration landfill leachate, ozone direct oxidation pretreatment and catalytic oxidation post-treatment coupled with anaerobic baffled membrane bioreactor (ABMBR) system was proposed in this study. For pretreatment, ozone direct oxidation could remarkably reduce UV254, 3D fluorescence peak value and fluorescence regional integration (FRI) of organic pollutants. For ABMBR treatment, the removal efficiencies of COD and ammonia nitrogen were 80.38% and 21.56%, respectively. Post-treatment included struvite precipitation, ozone catalytic oxidation and membrane bioreactor (MBR) treatment. Finally, the total removal efficiencies of COD and ammonia nitrogen were 91.2% and 99.4%, respectively. The chroma was remarkably decreased from 1250 times to 40 times after a series of treatments. The acids in ABMBR could be degraded by microorganisms of Proteobacteria and Chloroflexi. The cellulose and polysaccharides could be decomposed by Bacteroidetes and ketones could be decomposed by Brevundimonas in ABMBR. Electron paramagnetic resonance (EPR) analysis indicated that the hydroxyl radicals were the main reactive oxygen species during the direct ozone oxidation process, while the superoxide radicals played an important role in the ozone catalytic oxidation process.

Phosphate substances transformation and vivianite formation in P-Fe containing sludge during the transition process of aerobic and anaerobic conditions.

Excess sludge was considered as a promising raw material for phosphorus recovery. In this study, the P-Fe containing sludge came from the aerobic membrane bioreactor with electrocoagulation (EC), which was refluxed to the anaerobic unit for iron reduction. Under anaerobic condition, the ORP and pH maintained at -350 mV and 7.5, which exactly met the conditions for vivianite formation. According to the analysis of X-ray polycrystalline diffraction (XRD) and field emission scanning electron microscopy (FE-SEM), the final product of the sludge after anaerobic condition was mainly vivianite. Microbial analysis showed that there were iron reducing bacteria (IRB) in sludge before and after anaerobic process, including Dechloromonas, Desulfovibrio. Aeromonas and Methanobacterium. During the transition process of aerobic and anaerobic conditions, amorphous phosphate substances in P-Fe containing sludge could be transformed vivianite just with long term standing, which could promote the recovery of phosphate resource from wastewater.