Low Carbon Loss from Long-Term Manure-Applied Soil during Abrupt Warming Is Realized through Soil and Microbiome Interplay.

Manure application is a global approach for enhancing soil organic carbon (SOC) sequestration. However, the response of SOC decomposition in manure-applied soil to abrupt warming, often occurring during diurnal temperature fluctuations, remains poorly understood. We examined the effects of long-term (23 years) continuous application of manure on SOC chemical composition, soil respiration, and microbial communities under temperature shifts (15 vs 25 °C) in the presence of plant residues. Compared to soil without fertilizer, manure application reduced SOC recalcitrance indexes (i.e., aliphaticity and aromaticity) by 17.45 and 21.77%, and also reduced temperature sensitivity (Q10) of native SOC decomposition, plant residue decomposition, and priming effect by 12.98, 15.98, and 52.83%, respectively. The relative abundances of warm-stimulated chemoheterotrophic bacteria and fungi were lower in the manure-applied soil, whereas those of chemoautotrophic Thaumarchaeota were higher. In addition, the microbial network of the manure-applied soil was more interconnected, with more negative connections with the warm-stimulated taxa than soils without fertilizer or with chemical fertilizer applied. In conclusion, our study demonstrated that the reduced loss of SOC to abrupt warming by manure application arises from C chemistry modification, less warm-stimulated microorganisms, a more complex microbial community, and the higher CO2 intercepting capability by Thaumarchaeota.

Organocatalytic Cloke-Wilson Rearrangement: Carbocation-Initiated Tandem Ring Opening/Cyclization of Cyclopropanes under Neutral Conditions.

We report a metal-, acid-, and base-free 2-(bromomethyl)naphthalene (2-BMN)-promoted organocatalytic Cloke-Wilson rearrangement of chain doubly activated cyclopropanes for the construction of 2,3-dihydrofurans via a carbocation-initiated tandem intramolecular ring-opening/recyclization process. The strategy is especially suitable for the construction of furan units in complex molecules, providing a solution to the problem of heavy-metal residues in dihydrofuran-containing drugs synthesized by traditional metal-based protocols. Thus, it is of potential interest in synthetic and medicinal chemistry.

Synthetic K+ Channels Constructed by Rebuilding the Core Modules of Natural K+ Channels in an Artificial System.

Different types of natural K+ channels share similar core modules and cation permeability characteristics. In this study, we have developed novel artificial K+ channels by rebuilding the core modules of natural K+ channels in artificial systems. All the channels displayed high selectivity for K+ over Na+ and exhibited a selectivity sequence of K+ ≈Rb+ during the transport process, which is highly consistent with the cation permeability characteristics of natural K+ channels. More importantly, these artificial channels could be efficiently inserted into cell membranes and mediate the transmembrane transport of K+ , disrupting the cellular K+ homeostasis and eventually triggering the apoptosis of cells. These findings demonstrate that, by rebuilding the core modules of natural K+ channels in artificial systems, the structures, transport behaviors, and physiological functions of natural K+ channels can be mimicked in synthetic channels.

Synthesis and biological activities of amino acids functionalized α-GalCer analogues.

Invariant natural killer T-cells (iNKT-cells) are promising targets for manipulating the immune system, which can rapidly release a large amount of Th1 and Th2 cytokines upon the engagement of their T cell receptor with glycolipid antigens presented by CD1d. In this paper, we wish to report a novel series of α-GalCer analogues which were synthesized by incorporation of l-amino acid methyl esters in the C-6' position of glycolipid. The evaluation of these synthetic analogues for their capacities to stimulate iNKT-cells into producing Th1 and Th2 cytokines both in vitro and in vivo indicated that they were potent CD1d ligands and could stimulate murine spleen cells into a higher release of the Th1 cytokine IFN-γ in vitro. In vivo, Gly-α-GalCer (1) and Lys-α-GalCer (3) showed more Th1-biased responses than α-GalCer, especially analogue 3 showed the highest selectivity for IFN-γ production (IFN-γ/IL-4 = 5.32) compared with α-GalCer (IFN-γ/IL-4 = 2.5) in vivo. These novel α-GalCer analogues might be used as efficient X-ray crystallographic probes to reveal the relationship between glycolipids and CD1d proteins in α-GalCer/CD1d complexes and pave the way for developing new potent immunostimulating agents.

Acylamino-Directed Specific Sequential Difunctionalizations of Anilides via Metal-Free Relay Reactions for p-Oxygen and o-Nitrogen Incorporation.

Novel acylamino-directed relay disubstitutions realize the sequential difunctionalizations of anilides (1) under mild and metal-free conditions for the first time. This [bis(trifluoroacetoxy)iodo]benzene (PIFA) and BF3·Et2O promoted straightforward reaction produces a series of p-acetoxyl- or p-alkoxyl- o-nitro- N-arylamides (2), which are key scaffolds of various drugs, functional materials, and bioactive molecules. The flexibility with respect to the functional groups in these products affords this novel protocol excellent versatility for synthetic applications.

Total Synthesis of the Proposed Structure of Penasulfate A: l-Arabinose as a Source of Chirality.

The total synthesis of putative penasulfate A was effectively achieved by a convergent strategy with a longest linear sequence of 14 steps and overall yield of 8.6%. The highlights of our strategy involved an E-selective olefin cross-metathesis, Suzuki cross-coupling, and a copper(I)-catalyzed coupling reaction.

Selective Cleavage of Inert Aryl C-N Bonds in N-Aryl Amides.

A highly selective, IBX-promoted reaction has been developed for the oxidative cleavage of inert C(aryl)-N bonds on secondary amides while leaving the C(carbonyl)-N bond unchanged. This metal-free reaction proceeds under mild conditions (HFIP/H2O, 25 °C), providing facile access to various useful primary amides, some of which would be otherwise unattainable using conventional aminolysis and hydrolysis approaches.

Oxidation of ß-Ketoamides: The Synthesis of Vicinal Tricarbonyl Amides.

A facile and direct oxidative reaction for the synthesis of vicinal tricarbonyl amides in moderate to excellent yields (53-88%) was developed starting from readily available ß-ketoamides in the presence of phenyliodine(III) bis(trifluoroacetate). The resulting products possess significant synthetic potential, making this approach a valuable addition to the group of traditional methods already available for the preparation of these molecules.

Pathogenesis of diabetic complications: Exploring hypoxic niche formation and HIF-1α activation.

Hypoxia is a common feature of diabetic tissues, which highly correlates to the progression of diabetes. The formation of hypoxic context is induced by disrupted oxygen homeostasis that is predominantly driven by vascular remodeling in diabetes. While different types of vascular impairments have been reported, the specific features and underlying mechanisms are yet to be fully understood. Under hypoxic condition, cells upregulate hypoxia-inducible factor-1α (HIF-1α), an oxygen sensor that coordinates oxygen concentration and cell metabolism under hypoxic conditions. However, diabetic context exploits this machinery for pathogenic functions. Although HIF-1α protects cells from diabetic insult in multiple tissues, it also jeopardizes cell function in the retina. To gain a deeper understanding of hypoxia in diabetic complications, we focus on the formation of tissue hypoxia and the outcomes of HIF-1α dysregulation under diabetic context. Hopefully, this review can provide a better understanding on hypoxia biology in diabetes.

Catalytic System-Controlled Regioselective 1,2- and 1,4-Carboannulations of [60]Fullerene.

Selective functionalization of fullerenes is an important but challenging topic in fullerene chemistry and synthetic chemistry. Here we present the first example of catalytic system-controlled regioselective 1,2- and 1,4-addition reactions for the flexible and efficient synthesis of novel 1,2- and 1,4-carbocycle-fused fullerenes via a palladium-catalyzed decarboxylative carboannulation process.

Diabetes-Induced Autophagy Dysregulation Engenders Testicular Impairment via Oxidative Stress.

Testes produce sperms, and gamete generation relies on a proper niche environment. The disruption of hierarchical regulatory homeostasis in Leydig or Sertoli cells may evoke a sterile phenotype in humans. In this study, we recapitulated type 2 diabetes mellitus by using a high-fat diet- (HFD-) fed mouse model to identify the phenotype and potential mechanism of diabetes-induced testicular impairment. At the end of the study, blood glucose levels, testosterone structure, testicular antioxidant capacity, and testosterone level and the expression of hypoxia-inducible factor- (HIF-) 1α, apoptosis-related protein cleaved-caspase3, and autophagy-related proteins such as LC3I/II, p62, and Beclin1 were evaluated. We found that long-term HFD treatment causes the development of diabetes mellitus, implicating increased serum glucose level, cell apoptosis, and testicular atrophy (P < 0.05 vs. Ctrl). Mechanistically, the results showed enhanced expression of HIF-1α in both Sertoli and Leydig cells (P < 0.05 vs. Ctrl). Advanced glycation end products (AGEs) were demonstrated to be a potential factor leading to HIF-1α upregulation in both cell types. In Sertoli cells, high glucose treatment had minor effects on Sertoli cell autophagy. However, AGE treatment stagnated the autophagy flux and escalated cell apoptosis (P < 0.05 vs. Ctrl+Ctrl). In Leydig cells, high glucose treatment was adequate to encumber autophagy induction and enhance oxidative stress. Similarly, AGE treatment facilitated HIF-1α expression and hampered testosterone production (P < 0.05 vs. Ctrl+Ctrl). Overall, these findings highlight the dual effects of diabetes on autophagy regulation in Sertoli and Leydig cells while imposing oxidative stress in both cell types. Furthermore, the upregulation of HIF-1α, which could be triggered by AGE treatment, may negatively affect both cell types. Together, these findings will help us further understand the molecular mechanism of diabetes-induced autophagy dysregulation and testicular impairment, enriching the content of male reproductive biology in diabetic patients.

Metagenomics reveals the increased antibiotics resistome through prokaryote rather than virome after overuse of rare earth element compounds.

Rare earth elements (REE) are extensively exploited in the agricultural ecosystems due to their various beneficial roles on plant growth. However, the ecotoxicological effects and environmental risk of REE are poorly assessed. Here, we investigated the effects of lanthanum and cerium nitrate on soil prokaryote and viral metal resistance genes (MRGs) and antibiotics resistance genes (ARGs) using a metagenomic-based approach. We found that relative abundances of prokaryote phyla Bacteroidetes and Chloroflexi decreased with increasing of both REE compounds. In addition, low level REE nitrate (0.05 and 0.1 mmol kg-1 soil) inhibited the viral family Phycodanaviridae, Rudiviridae, Schitoviridae, whereas high level (0.16 and 0.32 mmol kg-1 soil) REE nitrate suppressed the viral family Herelleviridae, Iridoviridae, Podoviridae. ARGs were not significantly affected by low level of REE nitrate. However, high level of both REEs nitrate increased the abundances of dominant prokaryote genes resisting to most of the drug classes, such as aminoglycoside, elfamycin, fluoroquinolone, macrolide, rifamycin. Abundance of MRGs in prokaryote did not change consistently with REE nitrate compound type and input rate. MRGs were only partially detected in the virome in some of the treatments, while ARGs was not detected in virome. Together, we demonstrated that overuse of REE nitrate in agriculture would increase the risk of dissemination of ARGs through prokaryotes but not virus, although viral community was substantially shifted.

Spatially Segregated MOF Bioreactor Enables Versatile Modular Glycoenzyme Assembly for Hierarchical Glycan Library Construction.

The multienzyme cascade has received growing attention to obtain structurally defined glycans in vitro. However, due to poor enzyme stability and low compatibility between glycoenzymes, artificially designed multienzyme pathways to access glycans are often inefficient. Herein, based on the strategy "Modular-Enzymes Assembly by Spatial Segregation" (MASS), we developed a universal immobilization platform to assemble multiple glycoenzymes in compartmentalized MOF particles, inside and outside, significantly reducing the undesired interference and cross-inhibitions. By changing the enzyme modules, a series of glycosyl donor, disaccharides, oligosaccharides, and polysaccharides bearing cofactor regeneration were efficiently prepared. This bioreactor was further successfully applied to the reaction system with high substrate concentration to demonstrate its industrial potential. This robust multienzyme immobilization platform should serve to promote the enzymatic synthesis of more complex glycans.

A Facile and Cost-Effective Method to Prepare Biodegradable Poly(ester urethane)s with Ordered Aliphatic Hard-Segments for Promising Medical Application as Long-Term Implants.

The article below describes a simple methodology to prepare cost-effective biodegradable poly(ester urethane)s (PEUs) with ordered hard segments (OHS) for medical application as long-term implants. A low-cost diurethane diol (1,4-butanediol-hexanediisocyanate-1,4-butanediol, BHB) was first designed and synthesized. Consequently, the BHB was employed as a chain extender to react with NCO-terminated poly(ε-caprolactone) to obtain PEUs. The molecular structural formats for BHB and PEUs were defined through NMR, FT-IR, and MS together with GPC, while the influence of OHS content on physical/chemical features for casted PEU films was investigated. The introduction of OHS could contribute to forming denser hydrogen-bonds, and consequently produce a compact network structure, resulting in great tensile capacity, low water absorption, and slow hydrolytic degradation rate by PEU films. PEU-2.0 films, which possessed the highest OHS content within PEUs, exhibited 40.6 MPa tensile strength together with 477% elongation at break, 4.3 wt % equilibrium water absorption and only 29.5% weight loss post-12 months' degradation. In addition, cytotoxicity analysis of film extracts indicated that the cell viability of all PEUs containing OHS exceeded 75%, indicating good cytocompatibility. Due to outstanding tensile features, high biostability, nontoxic and absorbable degradation products and acceptable cytocompatibility, the cost-effective materials exhibited promising applications in the field of long-term implants.

Clinical Application of Shock Wave in the Treatment of Avascular Necrosis of the Femoral Head in the Early and Middle Stages.

In order to observe the clinical efficacy of shock waves in the treatment of avascular necrosis of the femoral head in the early and middle stages, a clinical application method of a shock wave in the treatment of avascular necrosis of the femoral head in the early and middle stages was proposed. The method combines the CT image segmentation technology to further segment the hip joint image, thereby speeding up the treatment speed and achieving a better treatment effect. Experimental results show that CT image segmentation takes 10.9 hours with an average time of 8 seconds, which is faster than other methods. The shock wave is an effective treatment method for early avascular necrosis of the femoral head, and this method will become one of the main methods for the clinical treatment of this kind of disease.

Transfer of IGF2BP3 Through Ara-C-Induced Apoptotic Bodies Promotes Survival of Recipient Cells.

Cytosine arabinoside (Ara-C) has been the standard therapeutic agent for myelodysplastic syndromes (MDS) and adult acute myeloid leukemia (AML) patients for decades. Considerable progress has been made in development of new treatments for MDS/AML patients, but drug resistance remains a major clinical problem. Apoptotic bodies (ABs), produced by late apoptotic cells, can enclose bioactive components that affect cell-cell interactions and disease progression. We isolated and identified drug-induced ABs from Ara-C-tolerance cells. Treatment of sensitive cells with Ara-C-induced ABs resulted in Ara-C-resistant phenotype. We further investigated components and functions of Ara-C-induced ABs. Proteomics analysis in combination with mass spectrometry revealed that Ara-C-induced ABs carried numerous RNA-binding proteins, notably including insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). Delivery of AB-encapsulated IGF2BP3 promoted survival of recipient cells by activating PI3K-AKT and p42-44 MAPK pathways. High IGF2BP3 level in ABs from MDS/AML patient plasma was correlated with poor overall survival. Our findings demonstrate that AB-derived IGF2BP3 plays an essential role in acquired Ara-C resistance in MDS/AML patients, and is a potential therapeutic target for suppression of Ara-C resistance.

Fabrication of pH-sensitive magnetic metal-organic framework for controlled-release of heparin.

Heparin, the most widely used anticoagulant drug in the world today, suffers from the risk of overdose and a short serum half-life, limiting its clinical applications. Concerning the controlled, sustained, and targeted release of heparin, a delivery system was fabricated in this research using the layered composites of Fe3O4 magnetic particles and pH-sensitive metal-organic framework, Fe3O4@ZIF-8. The composite demonstrated a high loading capacity for the heparin, 66.8 mg/g. The composite had a saturation magnetization of 1.5 emu/g and thus owned a magnetic targeting function, i.e. drug can be centered at a certain point using an external magnetic field. The anticoagulant activity was assessed by monitoring their activated partial thromboplastin time. The results showed that the pH-responsive and sustained release of the heparin reduced the systemic adverse effects associated with high concentrations. Moreover, control over the dose exhibited excellent anticoagulant features with fewer side effects.

MAPK CcSakA of the HOG Pathway Is Involved in Stipe Elongation during Fruiting Body Development in Coprinopsis cinerea.

Mitogen-activated protein kinase (MAPK) pathways, such as the high-osmolarity glycerol mitogen-activated protein kinase (HOG) pathway, are evolutionarily conserved signaling modules responsible for transmitting environmental stress signals in eukaryotic organisms. Here, we identified the MAPK homologue in the HOG pathway of Coprinopsis cinerea, which was named CcSakA. Furthermore, during the development of the fruiting body, CcSakA was phosphorylated in the fast elongating apical part of the stipe, which meant that CcSakA was activated in the apical elongating stipe region of the fruiting body. The knockdown of CcSakA resulted in a shorter stipe of the fruiting body compared to the control strain, and the expression of phosphomimicking mutant CcSakA led to a longer stipe of the fruiting body compared to the control strain. The chitinase CcChiE1, which plays a key role during stipe elongation, was downregulated in the CcSakA knockdown strains and upregulated in the CcSakA phosphomimicking mutant strains. The results indicated that CcSakA participated in the elongation of stipes in the fruiting body development of C. cinerea by regulating the expression of CcChiE1. Analysis of the H2O2 concentration in different parts of the stipe showed that the oxidative stress in the elongating part of the stipe was higher than those in the non-elongating part. The results indicated that CcSakA of the HOG pathway may be activated by oxidative stress. Our results demonstrated that the HOG pathway transmits stress signals and regulates the expression of CcChiE1 during fruiting body development in C. cinerea.

Investigating bacterial coupled assimilation of fertilizer­nitrogen and crop residue­carbon in upland soils by DNA-qSIP.

Microbial immobilization of fertilizer nitrogen (N) can effectively reduce N losses in soil. However, the effects of crop residue on microbial assimilation of fertilizer-N and the underlying microbial mechanisms in upland soils are unclear. We evaluated the influence of maize residue (13C) addition on the microbial assimilation of ammonium-N (15N) in DNA from fertilizer, and quantified the bacterial 13C or 15N assimilation by quantitative stable isotope probing (DNA-qSIP). We found that the straw addition did increase total microbial assimilation of ammonium from fertilizer during the 2-week incubation. However, bacterial taxa varied in their responses to straw addition: Bacteriodetes and Proteobacteria accounted for large fractions of ammonium assimilation and their N assimilations were increased, while N assimilations of Acidobacteria were decreased. We revealed that highly 13C-labeled taxa were the main contributors of N assimilation under straw addition. The straw primarily enhanced the contributions of bacterial taxa to ammonium assimilation through increasing the extent of N assimilation, or enhancing the abundance of the N-assimilating bacterial taxa. Overall, our study elucidated an interaction between microbial assimilation of fertilizer-N and straw-C, showing a close element coupling of the keystone functional microbial taxa in N immobilization driven by organic carbon.

Keystone microbial taxa drive the accelerated decompositions of cellulose and lignin by long-term resource enrichments.

Lignin and cellulose are the most important component of crop straw entering arable soil. The decomposition of lignin and cellulose are related to carbon sequestration and soil fertility. The keystone microbes decomposing lignin and cellulose in cropland and their impact on agricultural management, however, remains largely unclear. In this study, we traced the carbon (C) from highly enriched 13C-labeled (atom% 13C = 99 %) lignin and cellulose to functional keystone microbes in soils of a 26-year fertilization field experiment with stable isotope probing (SIP). 13C-cellulose and 13C-lignin decomposition were significantly accelerated with the long-term application of fertilization, especially with the combination of organic and chemical fertilization (NPKM). The 13C was mainly assimilated by bacteria Acidobacteria (i.e. GP1, GP3, GP6), Proteobacteria (i.e. unidentified gamaproteobactiera, Bradyrhizobium), and fungi Ascomycota (i.e. Talaromyces and Fusarium, etc.). The keystone bacteria taxa decomposing cellulose and lignin were large overlapped, but substantially shaped by fertilization. For instance, GP3 was the dominant bacterium that decomposed both cellulose and lignin in no fertilizer control (CK), while GP1 and GP6 were the ones in chemical fertilization (NPK) and NPKM, respectively. The decomposition rates of cellulose in different fertilizations were majorly predicted by soil total phosphorus (TP), functional fungi abundance, total nitrogen (TN), whereas functional bacterial and fungal abundance, TP, and community structure of functional fungi manipulated the decomposing rate of lignin. Together, we demonstrate that keystone functional microbes decomposing cellulose and lignin were largely concurring and significantly altered by long-term resources enrichment, which drives the similar patterns of decomposition rates of these two substrates along the resource enrichment gradient.