Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission.

Schizophrenia affects approximately 1% of the world population. Genetics, epigenetics, and environmental factors are known to play a role in this psychiatric disorder. While there is a high concordance in monozygotic twins, about half of twin pairs are discordant for schizophrenia. To address the question of how and when concordance in monozygotic twins occur, we have obtained fibroblasts from two pairs of schizophrenia discordant twins (one sibling with schizophrenia while the second one is unaffected by schizophrenia) and three pairs of healthy twins (both of the siblings are healthy). We have prepared iPSC models for these 3 groups of patients with schizophrenia, unaffected co-twins, and the healthy twins. When the study started the co-twins were considered healthy and unaffected but both the co-twins were later diagnosed with a depressive disorder. The reprogrammed iPSCs were differentiated into hippocampal neurons to measure the neurophysiological abnormalities in the patients. We found that the neurons derived from the schizophrenia patients were less arborized, were hypoexcitable with immature spike features, and exhibited a significant reduction in synaptic activity with dysregulation in synapse-related genes. Interestingly, the neurons derived from the co-twin siblings who did not have schizophrenia formed another distinct group that was different from the neurons in the group of the affected twin siblings but also different from the neurons in the group of the control twins. Importantly, their synaptic activity was not affected. Our measurements that were obtained from schizophrenia patients and their monozygotic twin and compared also to control healthy twins point to hippocampal synaptic deficits as a central mechanism in schizophrenia.

Core-shell structured carbon dots with up-conversion fluorescence and photo-triggered nitric oxide-releasing properties.

Cancer-targeted nanotechnology has a new trend in the design and preparation of new materials with functions for imaging and therapeutic applications simultaneously. As a new type of carbon nanomaterial, the inherent core-shell structured carbon dots (CDs) can be designed to provide a modular nanoplatform for integration of bioimaging and therapeutic capabilities. Here, core-shell structured CDs are designed and synthesized from levofloxacin and arginine and named Arg-CDs, in which levofloxacin-derived chromophores with up-conversion fluorescence are densely packed into the carbon core while guanidine groups are located on the shell, providing nitric oxide (NO) for photodynamic therapy of tumors. Moreover, the chromophores in the carbon core irradiated by visible LED light generate large amounts of reactive oxygen species (ROSs) that will oxidize the guanidine groups located on the shell of the Arg-CDs and further increase the NO releasing capacity remarkably. The as-synthesized Arg-CDs show excellent biocompatibility, bright up-conversion fluorescence, and a light-controlled ROS & NO releasing ability, which can be a potential light-modulated nanoplatform to integrate bioimaging and therapeutic functionalities.

Soil mineral nitrogen regulation by a novel porous material in structurally degraded soils.

BACKGROUND: The availability of soil nitrogen (N) decreases as the structure of agricultural soils degrades. Traditional methods focus on organic amendments that indirectly affect the porosity and N content of soil. Due to the low efficiency of such amendments, new materials, particularly highly porous materials, are needed to improve the quality of soil, which has opened new directions. RESULTS: The addition of 2 to 7 mm of porous clay ceramic (PLC) significantly increased the fresh weight of Brassica chinensis. The soil aeration porosity (>50 µm) increased by 0.69% on average in response to 1% PLC application. Soil NO3 - -N, NH4 + -N and mineral N increased by 3.3, 1.3 and 4.6 mg kg-1 on average, respectively, following a 1% PLC application rate. The initial N content of the high PLC treatments was the lowest in the incubation experiment. The parameters of soil N mineralization, i.e. potentially mineralizable N (N0 ), the first-order rate constant (k) and the mineralization composite index (N0  × k), increased obviously as the amount of PLC increased. Porosities larger than 1000 µm were significantly more positively correlated with the parameters of soil N mineralization than those <500 µm. The Pearson correlation coefficients suggested that high porosity, mineral N and N0 values had significant positive relationships with the fresh weights in double seasons. CONCLUSION: The application of PLC increased soil aeration and enhanced the availability of soil N, which yielded large vegetable harvests in clayey soils in the short term. © 2022 Society of Chemical Industry.

Stepwise increase of thaxtomins production in Streptomyces albidoflavus J1074 through combinatorial metabolic engineering.

Herbicide-resistance in weeds has become a serious threat to agriculture across the world. Thus, there is an urgent need for the discovery and development of herbicides with new modes of action. Thaxtomin phytotoxins are a group of nitrated diketopiperazines produced by potato common scab-causing phytopathogen Streptomyces scabies and other actinobacterial pathogens. They are generally considered to function as inhibitors of cellulose synthesis in plants, and thus have great potential to be used as natural herbicides. Generation of an overproducing strain is crucial for the scale-up production of thaxtomins and their wide use in agriculture. In the present study, we employed a stepwise strategy by combining heterologous expression, repressor deletion, activator overexpression, and optimization of fermentation media for high-level production of thaxtomins. The maximum yield of 728 mg/L thaxtomins was achieved with engineered Streptomyces albidoflavus J1074 strains in shake-flask cultures, and it was approximately 36-fold higher than S. albidoflavus J1074 carrying the unmodified cluster. Moreover, the yield of thaxtomins could reach 1973 mg/L when the engineered strain was cultivated in a small-scale stirred-tank bioreactor. This is the highest titer reported to date, representing a significant leap forward for the scale-up production of thaxtomins. Our study presents a robust, easy-to-use system that will be broadly useful for improving titers of bioactive compounds in many Streptomyces species.

Synthetic far-red light-mediated CRISPR-dCas9 device for inducing functional neuronal differentiation.

The ability to control the activity of CRISPR-dCas9 with precise spatiotemporal resolution will enable tight genome regulation of user-defined endogenous genes for studying the dynamics of transcriptional regulation. Optogenetic devices with minimal phototoxicity and the capacity for deep tissue penetration are extremely useful for precise spatiotemporal control of cellular behavior and for future clinic translational research. Therefore, capitalizing on synthetic biology and optogenetic design principles, we engineered a far-red light (FRL)-activated CRISPR-dCas9 effector (FACE) device that induces transcription of exogenous or endogenous genes in the presence of FRL stimulation. This versatile system provides a robust and convenient method for precise spatiotemporal control of endogenous gene expression and also has been demonstrated to mediate targeted epigenetic modulation, which can be utilized to efficiently promote differentiation of induced pluripotent stem cells into functional neurons by up-regulating a single neural transcription factor, NEUROG2 This FACE system might facilitate genetic/epigenetic reprogramming in basic biological research and regenerative medicine for future biomedical applications.

Economics- and policy-driven organic carbon input enhancement dominates soil organic carbon accumulation in Chinese croplands.

China's croplands have experienced drastic changes in management practices, such as fertilization, tillage, and residue treatments, since the 1980s. There is an ongoing debate about the impact of these changes on soil organic carbon (SOC) and its implications. Here we report results from an extensive study that provided direct evidence of cropland SOC sequestration in China. Based on the soil sampling locations recorded by the Second National Soil Survey of China in 1980, we collected 4,060 soil samples in 2011 from 58 counties that represent the typical cropping systems across China. Our results showed that across the country, the average SOC stock in the topsoil (0-20 cm) increased from 28.6 Mg C ha-1 in 1980 to 32.9 Mg C ha-1 in 2011, representing a net increase of 140 kg C ha-1 year-1 However, the SOC change differed among the major agricultural regions: SOC increased in all major agronomic regions except in Northeast China. The SOC sequestration was largely attributed to increased organic inputs driven by economics and policy: while higher root biomass resulting from enhanced crop productivity by chemical fertilizers predominated before 2000, higher residue inputs following the large-scale implementation of crop straw/stover return policy took over thereafter. The SOC change was negatively related to N inputs in East China, suggesting that the excessive N inputs, plus the shallowness of plow layers, may constrain the future C sequestration in Chinese croplands. Our results indicate that cropland SOC sequestration can be achieved through effectively manipulating economic and policy incentives to farmers.

Citrus flavonoids and the intestinal barrier: Interactions and effects.

The intestinal barrier plays a central role in sustaining gut homeostasis and, when dysfunctional, may contribute to diseases. Dietary flavonoids derived from Citrus genus represent one of the main naturally occurring phytochemicals with multiple potential benefits for the intestinal barrier function. In the intestine, citrus flavonoids (CFs) undergo ingestion from the lumen, biotransformation in the epithelial cells and/or crosstalk with luminal microbiota to afford various metabolites that may in turn exert protective actions on gut barrier along with their parental compounds. Specifically, the health-promoting properties of CFs and their metabolic bioactives for the intestinal barrier include their capacity to (a) modulate barrier permeability; (b) protect mucus layer; (c) regulate intestinal immune system; (d) fight against oxidative stress; and (e) positively shape microbiome and metabolome. Notably, local effects of CFs can also generate systemic benefits, for instance, improvement of gut microbial dysbiosis helpful to orchestrate gut homeostasis and leading to alleviation of systemic dysmetabolism. Given the important role of the intestinal barrier in overall health, further understanding of underlying action mechanisms and ultimate health effects of CFs as well as their metabolites on the intestine is of great significance to future application of citrus plants and their bioactives as dietary supplements and/or functional ingredients in medical foods.

Copper-Catalyzed and Proton-Directed Selective Hydroxymethylation of Alkynes with CO2.

An intriguing strategy for copper-catalyzed hydroxymethylation of alkynes with CO2 and hydrosilane was developed. Switched on/off a proton source, for example, t BuOH, direct hydroxymethylation and reductive hydroxymethylation could be triggered selectively, delivering a series of allylic alcohols and homobenzylic alcohols, respectively, with high levels of Z/E, regio- and enantioselectivity. Such a selective synthesis is attributed to the differences in response of vinylcopper intermediate to proton and CO2 . The protonation of vinylcopper species is demonstrated to be prior to hydroxymethylation, thus allowing a diversion from direct alkyne hydroxymethylation to reductive hydroxymethylation in the presence of suitable proton.

IDO1 Maintains Pluripotency of Primed Human Embryonic Stem Cells by Promoting Glycolysis.

Human embryonic stem cells (hESCs) depend on glycolysis for energy supply and pluripotency and switch to oxidative phosphorylation upon differentiation. The underlying mechanisms remain unclear. Here, we demonstrate that indoleamine 2,3-dioxygenase 1 (IDO1) is expressed in primed hESCs and its expression rapidly downregulated upon hESC differentiation. IDO1 is required to maintain pluripotency by suppressing mitochondria activity and promoting glycolysis through the increase of NAD+ /NADH ratio. The upregulation of IDO1 during hESC differentiation suppresses the differentiation of hESCs into certain lineages of cells such as cardiomyocytes, which depend on oxidative phosphorylation to satisfy their high energy demand. Therefore, IDO1 plays important roles in maintaining the pluripotency of hESCs. Stem Cells 2019;37:1158-1165.

Engineered biosynthesis of thaxtomin phytotoxins.

Herbicide-resistant weeds are a growing problem worldwide. Thaxtomin phytotoxins are a group of nitrated diketopiperazines produced by the potato common scab-causing pathogen Streptomyces scabies and other actinobacterial plant pathogens. They represent a unique class of microbial natural products with distinctive structural features and promising herbicidal activity. The biosynthesis of thaxtomins proceeds through multiple steps of unusual enzymatic reactions. Advances in understanding of thaxtomins biosynthetic machinery have provided the basis for precursor-directed biosynthesis, pathway refactoring, and one-pot biocombinatorial synthesis to generate thaxtomin analogues. We herein summarize recent findings on the biosynthesis of thaxtomins and highlight recent advances in the rational generation of novel thaxtomins for the development of potent herbicidal agents.

Template-induced Al distribution in MOR and enhanced activity in dimethyl ether carbonylation.

As the activity of dimethyl ether (DME) carbonylation over mordenite proportionally correlates with the Brønsted acid sites (BAS) in 8-membered ring (8-MR), enhancing the concentration of BAS in the 8-MR of MOR is important to improve the efficiency of the reaction. Herein, we report that the distribution of the BAS in the zeolite catalyst H-MOR can be altered by the synthesis of H-MOR with different cyclic amine structure-directing templates, several of which have not been reported previously for MOR synthesis. By combining FTIR, ICP, TG analysis and DFT calculations, it is verified that the strength of the interaction between amine or sodium cations and [AlO4]- in the zeolite framework plays a decisive role in Al distribution, owing to the competitive effect between Na+ and the cyclic amine compensating negative charges from the framework [AlO4]-. Quantitative analysis of the BAS in the 12-MR and 8-MR identifies the optimum template for maximizing the BAS in the 8-MR. It is shown that the enhanced activity of the H-MOR for the DME carbonylation to methyl acetate correlates with the increase in the BAS in the 8-MR. Our finding thus provides a facile strategy to direct Al location within different channels of the zeolite, which must benefit spatially confined reaction systems.

Chain Transfer to Toluene in Styrene Coordination Polymerization.

The chain-transfer reaction is rather important in coordination polymerization regarding catalytic efficiency, adjustment of molecular weight, and control of chain structure. To date, chain transfer to H2 and Al, Mg, and Zn alkyl compounds and ß-H elimination are the commonly encountered modes. Now a novel chain transfer to toluene is reported. By introducing fluorine atoms into the ß-diketimine ligands, an inert catalytic system for styrene (St) coordination polymerization was transferred into the highly active one. The activity increased with an increase in the number of fluorines in the ligands. Surprisingly, the molecular weights of resultant polystyrenes are very low (Mn =2000-6600 Da) despite of St loadings, corresponding up to 121 chains per active species. The mechanisms were investigated by DFT simulation, MALDI-TOF MS, isotope tracing experiment and 2D NMR spectrum analyses, which revealed that the fluorine activated the polymerization and directed chain transfer to toluene.

The Effect of Carbonic Maceration during Winemaking on the Color, Aroma and Sensory Properties of 'Muscat Hamburg' Wine.

This is the first study on the effect of carbonic maceration on the quality (color, aroma profile and sensory properties) of Muscat Hamburg, contrasting two winemaking procedures used in Tianjin (classical white and red-winemaking techniques). The values of C* (psychometric chroma), a* (measure of redness) and b* (measure of yellowness) were significantly higher (p < 0.01) in the carbonic macerated wine than in red wine. However, there were no visual differences in color, and classical red wine and carbonic macerated wine had similar h (hue angle) values and located in the red region. Thirty-two aromatic compounds were identified and quantified in Muscat Hamburg wines. The content of volatile compounds (6384.97 µg/L) was significantly higher (p < 0.001) in the carbonic macerated Muscat Hamburg wine than in the other kinds of wine. This result led to the carbonic macerated wine having the highest odor activity values (OAVs) and sensory evaluation scores (86.8 points), which correlates with an "excellent" sensory perception. This study demonstrated that carbonic maceration significantly improved the quality of Muscat Hamburg wine based on volatile analysis and sensory evaluation compared with other conventional methods. Therefore, carbonic maceration could be well suited for making Muscat Hamburg wine.

Antioxidant Activity Evaluation of Dietary Flavonoid Hyperoside Using Saccharomyces Cerevisiae as a Model.

Oxidative stress leads to various diseases, including diabetes, cardiovascular diseases, neurodegenerative diseases, and even cancer. The dietary flavonol glycoside, hyperoside (quercetin-3-O-galactoside), exerts health benefits by preventing oxidative damage. To further understand its antioxidative defence mechanisms, we systemically investigated the regulation of hyperoside on oxidative damage induced by hydrogen peroxide, carbon tetrachloride, and cadmium in Saccharomyces cerevisiae. Hyperoside significantly increased cell viability, decreased lipid peroxidation, and lowered intracellular reactive oxygen species (ROS) levels in the wild-type strain (WT) and mutants gtt1∆ and gtt2∆. However, the strain with ctt1∆ showed variable cell viability and intracellular ROS-scavenging ability in response to the hyperoside treatment upon the stimulation of H2O2 and CCl4. In addition, hyperoside did not confer viability tolerance or intercellular ROS in CdSO4-induced stress to strains of sod1∆ and gsh1∆. The results suggest that the antioxidative reactions of hyperoside in S. cerevisiae depend on the intercellular ROS detoxification system.

Step-Growth Coordination Polymerization of 5-Hydroxymethyl Furfural with Dihydrosilanes: Synergistic Catalysis Using Heteroscopionate Zinc Hydride and B(C6 F5 )3.

The utilization of 5-hydroxymethyl furfural (HMF) as a renewable feedstock for polymer synthesis has not yet been achieved as it is structurally asymmetric and contains three active functional groups. Reported here is the unprecedented step-growth copolymerization of HMF and dihydrosilanes, through a coordination mechanism, to afford linear poly(silyl ether)s in the presence of B(C6 F5 )3 and the heteroscorpionate zinc hydride complex LZnH [L=(Me Pz)2 CP(Ph)2 NPh, Me Pz=3,5-dimethylpyrazolyl]. The adduct B(C6 F5 )3 ⋅⋅⋅H⋅⋅⋅Zn, confirmed by NMR spectroscopy and DFT calculations, plays a key role in the synergistic catalysis, where B(C6 F5 )3 activates ZnH and stabilizes the Zn+ active species, and the sterically bulky ZnH effectively inhibits (C6 F5 )3 B from reacting with dihydrosilane to form (C6 F5 )3 B-H-Si, which facilely initiates ring opening of furan. The mechanism was studied by DFT simulations.

Molecular evolution of the plastid genome during diversification of the cotton genus.

Cotton (Gossypium spp.) is commonly grouped into eight diploid genomic groups, designated A-G and K, and one tetraploid genomic group, namely AD. To gain insight into the phylogeny of Gossypium and molecular evolution of the chloroplast genome duringdiversification, chloroplast genomes (cpDNA) from 6 D-genome and 2 G-genome species of Gossypium (G. armourianum D2-1, G. harknessii D2-2, G. davidsonii D3-d, G. klotzschianum D3-k, G. aridum D4, G. trilobum D8, and G. australe G2, G. nelsonii G3) were newly reported here. In combination with the 26 previously released cpDNA sequences, we performed comparative phylogenetic analyses of 34 Gossypium chloroplast genomes that collectively represent most of the diversity in the genus. Gossypium chloroplasts span a small range in size that is mostly attributable to indels that occur in the large single copy (LSC) region of the genome. Phylogenetic analysis using a concatenation of all genes provides robust support for six major Gossypium clades, largely supporting earlier inferences but also revealing new information on intrageneric relationships. Using Theobroma cacao as an outgroup, diversification of the genus was dated, yielding results that are in accord with previous estimates of divergence times, but also offering new perspectives on the basal, early radiation of all major clades within the genus as well as gaps in the record indicative of extinctions. Like most higher-plant chloroplast genomes, all cotton species exhibit a conserved quadripartite structure, i.e., two large inverted repeats (IR) containing most of the ribosomal RNA genes, and two unique regions, LSC (large single sequence) and SSC (small single sequence). Within Gossypium, the IR-single copy region junctions are both variable and homoplasious among species. Two genes, accD and psaJ, exhibited greater rates of synonymous and non-synonymous substitutions than did other genes. Most genes exhibited Ka/Ks ratios suggestive of neutral evolution, with 8 exceptions distributed among one to several species. This research provides an overview of the molecular evolution of a single, large non-recombining molecular during the diversification of this important genus.

A Zinc Finger Protein Regulates Flowering Time and Abiotic Stress Tolerance in Chrysanthemum by Modulating Gibberellin Biosynthesis.

Flowering time and an ability to tolerate abiotic stresses are important for plant growth and development. We characterized BBX24, a zinc finger transcription factor gene, from Chrysanthemum morifolium and found it to be associated with both flowering time and stress tolerance. Transgenic lines with suppressed expression of Cm-BBX24 (Cm-BBX24-RNAi) flowered earlier than wild-type plants and showed decreased tolerance to freezing and drought stresses. Global expression analysis revealed that genes associated with both photoperiod and gibberellin (GA) biosynthesis pathways were upregulated in Cm-BBX24-RNAi lines, relative to the wild type. By contrast, genes that were upregulated in overexpressing lines (Cm-BBX24-OX), but downregulated in Cm-BBX24-RNAi lines (both relative to the wild type), included genes related to compatible solutes and carbohydrate metabolism, both of which are associated with abiotic stress. Cm-BBX24 expression was also influenced by daylength and GA4/7 application. Under long days, changes in endogenous GA1, GA4, GA19, and GA20 levels occurred in young leaves of transgenic lines, relative to the wild type. Regulation of flowering involves the FLOWERING TIME gene, which integrates photoperiod and GA biosynthesis pathways. We postulate that Cm-BBX24 plays a dual role, modulating both flowering time and abiotic stress tolerance in chrysanthemum, at least in part by influencing GA biosynthesis.

Rapid Syndiospecific (Co)Polymerization of Fluorostyrene with High Monomer Conversion.

Fluoromonomers are difficult to polymerize through a coordination mechanism owing to the strong chelation between fluorine and catalysts and the electron-deficient double-bond. We report herein the unprecedented polymerization of para-fluorostyrene (pFS) with excellent activity (1.12×107  g molLn-1 h-1 ), distinguished syndioselectivity (rrrr >99 %) and high conversion (98.4 %) using rare-earth-metal catalysts bearing a pyridyl methylene fluorenyl ligand. DFT calculations reveal polar fluorine loses overwhelming coordination priority to the active central metal ion due to the sterically bulky and electron-donating CGC-ligand, thus its power of poisoning the active species is dramatically weakened. Based on this, copolymerization of pFS and styrene (St) has been successfully achieved with high activity and controllable pFS insertion. Conversely, the unlinked half-sandwich rare-earth-metal system shows relatively lower activity, because both the transition-states and intermediates incorporate a µ1 -F chelated pFS.

Characteristics of syphilitic uveitis in northern China.

BACKGROUND: To describe the characteristics of patients with syphilitic uveitis in northern China. METHODS: A case series of 21 patients (33 eyes) diagnosed with syphilitic uveitis from 2011 to 2016 at a tertiary center in northern China was retrospectively analyzed. RESULTS: Twenty-one patients (33 eyes) were diagnosed as syphilitic uveitis. Posterior segment involvement was found in 32 eyes (97.0%). Vitreous haze, neuroretinitis, and posterior placoid chorioretinitis were mainly found in patients with a relatively short duration of the disease, while diffuse chorioretinitis, pseudoretinitis pigmentosa, cystoid macular edema, and epiretinal membrane were found in patients with relatively long duration of ocular involvement. A low best-corrected visual acuity (P = 0.022) and a delay of syphilis treatment (P < 0.001) were associated with a significantly worse visual outcome. CONCLUSIONS: Syphilitic uveitis should be included in the differential diagnosis of any form of posterior ocular inflammation. The pattern of ocular involvement may change with the disease progression.

cis-1,4-Selective Copolymerization of Ethylene and Butadiene: A Compromise between Two Mechanisms.

Introducing ethylene units into polybutadiene backbones is an approach to synthesize advanced rubber materials, which has been a research challenge because of distinct polymerization mechanisms of the two monomers. To date, only trans-1,4- and 1,2-regulated copolymers have been obtained. Herein, we reported the unprecedented cis-1,4 selective copolymerization of ethylene and butadiene by using the thiophene-fused cyclopentadienyl-ligated scandium complexes. The effects of the sterics and electronics of the catalytic precursors as well as the monomer loading mode on the activity and selectivity as well as the sequence lengths were investigated, and the mechanism was elucidated. Thus a novel ethylene-based rubber material possessing a high molecular weight, 80 % cis-1,4 regularity and a Tg =-94 °C without an obvious melting point owing to short polyethylene sequences even at its content up to 45 mol %, was isolated. This new rubber material exhibited excellent anti-flowing performance and strong tensile strength.