Biotransformation approach to produce rare ginsenosides F1, compound Mc1, and Rd2 from major ginsenosides.

The stems and leaves of Panax notoginseng contain high saponins, but they are often discarded as agricultural waste. In this study, the predominant ginsenosides Rg1, Rc, and Rb2, presented in the stems and leaves of ginseng plants, were biotransformed into value-added rare ginsenosides F1, compound Mc1 (C-Mc1), and Rd2, respectively. A fungal strain YMS6 (Penicillium sp.) was screened from the soil as a biocatalyst with high selectivity for the deglycosylation of major ginsenosides. Under the optimal fermentation conditions, the yields of F1, C-Mc1, and Rd2 were 97.95, 68.64, and 79.58%, respectively. This study provides a new microbial resource for the selective conversion of protopanaxadiol-type and protopanaxatriol-type major saponins into rare ginsenosides via the whole-cell biotransformation and offers a solution for the better utilization of P. notoginseng waste.

Quantitative analysis of index factors in agricultural compost by infrared spectroscopy.

Hyperspectral technology, with its high spectrum resolution and nanometer continuous spectral information acquisition ability, provide a possibility for rapidly and nondestructive evaluating compost maturity. In this study, the near-infrared spectroscopy (NIRS) analysis techniques was used to analyze quantitatively organic matter (OM) content, total nitrogen (TN) content and carbon-nitrogen (C/N) ratio in compost based on two different composting procedures. In the basis of spectra preprocessing and strategies of variable selection, the nonlinear modeling LBC-siPLS-PLSR for OM, MSC-SPA-PLSR for TN and R-SPA-PLSR for C/N ratio was respectively constructed using partial least squares regression (PLSR). LBC-siPLS-PLSR, MSC-SPA-PLSR and R-SPA-PLSR provided a better prediction capability with root mean square error of prediction, the coefficient of determination for prediction and residual predictive deviation values of 4.061, 0.746 and 2.02 for OM, values of 0.205, 0.65 and 1.71 for TN and values of 1.11, 0.706 and 2.07 for C/N ratio, respectively. These results showed that the NIRS technique could be fitted to each element, using specific spectrum pretreatment, in order to achieve an acceptable accuracy in the prediction.

Altered functional dynamics gradient in schizophrenia with cigarette smoking.

Schizophrenia is associated with a high prevalence of cigarette smoking. Neural dynamics are spatially structured and shaped by both microscale molecular and macroscale functional architectures, which are disturbed in the diseased brain. The neural mechanism underlying the schizophrenia-nicotine dependence comorbidity remains unknown. In this study, we aimed to test whether there is an interaction between schizophrenia and smoking in brain neural dynamics, and how the main effect of the 2 factors related to the molecular architecture. Functional magnetic resonance imaging data were obtained from 4 groups: schizophrenia and healthy controls with/without smoking. We identified 2 dynamics gradients combined with over 5,000 statistical features of the brain region's time series. The interaction effect was found in the high-order functional network, and the main effect of schizophrenia was in the bilateral orbitofrontal cortices. Moreover, the disease- and smoking-related alteration in brain pattern was associated with spatial distribution of serotonin, cannabinoid, and glutamate. Collectively, these findings supported the self-medication hypothesis in schizophrenia-nicotine dependence with a neural intrinsic dynamics perspective.

Shared and distinct patterns of dynamic functional connectivity variability of thalamo-cortical circuit in bipolar depression and major depressive disorder.

Evidence has indicated abnormalities of thalamo-cortical functional connectivity (FC) in bipolar disorder during a depressive episode (BDD) and major depressive disorder (MDD). However, the dynamic FC (dFC) within this system is poorly understood. We explored the thalamo-cortical dFC pattern by dividing thalamus into 16 subregions and combining with a sliding-window approach. Correlation analysis was performed between altered dFC variability and clinical data. Classification analysis with a linear support vector machine model was conducted. Compared with healthy controls (HCs), both patients revealed increased dFC variability between thalamus subregions with hippocampus (HIP), angular gyrus and caudate, and only BDD showed increased dFC variability of the thalamus with superior frontal gyrus (SFG), HIP, insula, middle cingulate gyrus, and postcentral gyrus. Compared with MDD and HCs, only BDD exhibited enhanced dFC variability of the thalamus with SFG and superior temporal gyrus. Furthermore, the number of depressive episodes in MDD was significantly positively associated with altered dFC variability. Finally, the disrupted dFC variability could distinguish BDD from MDD with 83.44% classification accuracy. BDD and MDD shared common disrupted dFC variability in the thalamo-limbic and striatal-thalamic circuitries, whereas BDD exhibited more extensive and broader aberrant dFC variability, which may facilitate distinguish between these 2 mood disorders.

New antibacterial depsidones from an ant-derived fungus Spiromastix sp. MY-1.

Six new (1-6) and seven known depsidones (7-13) were isolated from the culture of an ant (Monomorium chinensis)-derived fungus Spiromastix sp. MY-1. Their structures were elucidated by extensive spectroscopic analysis including high resolution MS, 1D and 2D NMR data. The new bromide depsidones were obtained through supplementing potassium bromide in the fermentation medium of Spiromastix sp. MY-1. All isolated compounds showed various bioactivities against the tested phytopathogenic bacteria. Particularly, new bromide compound 4, named spiromastixone S, exhibited the strongest activity against Xanthomonas oryzae pv. oryzae with a MIC value of 5.2 µmol·-1.

Genetic encoding of ε-N-L-lactyllysine for detecting delactylase activity in living cells.

Lysine ε-N-L-lactylation is a newly discovered post-translational modification. Herein we present the genetic encoding of ε-N-L-lactyllysine in bacterial and mammalian cells, allowing the preparation of site-specifically ε-N-L-lactylated recombinant proteins and the construction of fluorescent and luminescent probes for detecting delactylases in living cells. Using these probes, we demonstrate sirtuin 1 as a potential delactylase for non-histone proteins.

A bioorthogonal chemical reporter for the detection and identification of protein lactylation.

l-Lactylation is a recently discovered post-translational modification occurring on histone lysine residues to regulate gene expression. However, the substrate scope of lactylation, especially that in non-histone proteins, remains unknown, largely due to the limitations of current methods for analyzing lactylated proteins. Herein, we report an alkynyl-functionalized bioorthogonal chemical reporter, YnLac, for the detection and identification of protein lactylation in mammalian cells. Our in-gel fluorescence and chemical proteomic analyses show that YnLac is metabolically incorporated into lactylated proteins and directly labels known lactylated lysines of histones. We further apply YnLac to the proteome-wide profiling of lactylation, revealing many novel modification sites in non-histone proteins for the first time. Moreover, we demonstrate that lactylation of a newly identified substrate protein PARP1 regulates its ADP-ribosylation activity. Our study thus provides a powerful chemical tool for characterizing protein lactylation and greatly expands our understanding of substrate proteins and functions of this new modification.

Fusobacterium nucleatum: The Opportunistic Pathogen of Periodontal and Peri-Implant Diseases.

Peri-implant diseases are considered to be a chronic destructive inflammatory destruction/damage occurring in soft and hard peri-implant tissues during the patient's perennial use after implant restoration and have attracted much attention because of their high incidence. Although most studies seem to suggest that the pathogenesis of peri-implant diseases is similar to that of periodontal diseases and that both begin with microbial infection, the specific mechanism of peri-implant diseases remains unclear. As an oral opportunistic pathogen, Fusobacterium nucleatum (F. nucleatum) has been demonstrated to be vital for the occurrence and development of many oral infectious diseases, especially periodontal diseases. More notably, the latest relevant studies suggest that F. nucleatum may contribute to the occurrence and development of peri-implant diseases. Considering the close connection between peri-implant diseases and periodontal diseases, a summary of the role of Fusobacterium nucleatum in periodontal diseases may provide more research directions and ideas for the peri-implantation mechanism. In this review, we summarize the effects of F. nucleatum on periodontal diseases by biofilm formation, host infection, and host response, and then we establish the relationship between periodontal and peri-implant diseases. Based on the above aspects, we discuss the importance and potential value of F. nucleatum in peri-implant diseases.

Irradiated Cell-Derived Exosomes Transmit Essential Molecules Inducing Radiation Therapy Resistance.

Radioresistance has always been a major obstacle in radiation therapy (RT) progress. Radiation therapy (RT) leads to changes in the contents of released exosomes. Research has shown that irradiated cell-derived exosomes influence recipient cell proliferation, migration, cell cycle arrest, and apoptosis. All evidence indicates that exosomes play a significant role in radioresistance. In this review, we describe the potential role of exosomes in cancer. We summarize that the irradiated cell-derived exosomes influence radioresistance in recipient cells by 3 main mechanisms: (1) enhancing DNA repair, (2) regulating cell death signaling pathways, and (3) inducing cancer cells to exhibit stem cell properties. We also discuss that the origin of the phenomenon might be the changes of molecular mechanisms of irradiated cell-derived exosomes formation affected by RT. Further, targeting exosomes as an adjuvant therapy might be a promising way for cancer treatments.

Antioxidative Stress: Inhibiting Reactive Oxygen Species Production as a Cause of Radioresistance and Chemoresistance.

Radiotherapy and chemotherapy are the most effective nonsurgical treatments for cancer treatment. They usually induce regulated cell death by increasing the level of reactive oxygen species (ROS) in tumour cells. However, as intracellular ROS concentration increases, many antioxidant pathways are concurrently upregulated by cancer cells to inhibit ROS production, ultimately leading to drug resistance. Understanding the mechanism of antioxidant stress in tumour cells provides a new research direction for overcoming therapeutic resistance. In this review, we address (1) how radiotherapy and chemotherapy kill tumour cells by increasing the level of ROS, (2) the mechanism by which ROS activate antioxidant pathways and the subsequent cellular mitigation of ROS in radiotherapy and chemotherapy treatments, and (3) the potential research direction for targeted treatment to overcome therapeutic resistance.

Site-specific chemical fatty-acylation for gain-of-function analysis of protein S-palmitoylation in live cells.

Protein S-palmitoylation, or S-fatty-acylation, regulates many fundamental cellular processes in eukaryotes. Herein, we present a chemical fatty-acylation approach that involves site-specific incorporation of cycloalkyne-containing unnatural amino acids and subsequent bioorthogonal reactions with fatty-acyl tetrazines to install fatty-acylation mimics at target protein sites, allowing gain-of-function analysis of S-palmitoylation in live cells.

Preparation of α-amino acids via Ni-catalyzed reductive vinylation and arylation of α-pivaloyloxy glycine.

This work emphasizes easy access to α-vinyl and aryl amino acids via Ni-catalyzed cross-electrophile coupling of bench-stable N-carbonyl-protected α-pivaloyloxy glycine with vinyl/aryl halides and triflates. The protocol permits the synthesis of α-amino acids bearing hindered branched vinyl groups, which remains a challenge using the current methods. On the basis of experimental and DFT studies, simultaneous addition of glycine α-carbon (Gly) radicals to Ni(0) and Ar-Ni(ii) may occur, with the former being more favored where oxidative addition of a C(sp2) electrophile to the resultant Gly-Ni(i) intermediate gives a key Gly-Ni(iii)-Ar intermediate. The auxiliary chelation of the N-carbonyl oxygen to the Ni center appears to be crucial to stabilize the Gly-Ni(i) intermediate.

Copper-Catalyzed and Indium-Mediated Methoxycarbonylation of Unactivated Alkyl Iodides with Balloon CO.

This work emphasizes the synthesis of alkyl esters via Cu-catalyzed and In-mediated alkoxycarbonylation of unactivated alkyl iodides in the presence of In or InI. The reactions were suitable for the preparation of primary, secondary, and even tertiary alkyl esters, representing an exceptionally rare example for the creation of quaternary carbon centers upon formation of esters. The preliminary mechanistic studies indicated that alkyl radicals were involved, and Cu/In/CO played a cooperative role in the carbonylation event.

Dynamic functional connectivity analysis reveals decreased variability of the default-mode network in developing autistic brain.

Accumulating neuroimaging evidence suggests that abnormal functional connectivity of the default mode network (DMN) contributes to the social-cognitive deficits of autism spectrum disorder (ASD). Although most previous studies relied on conventional functional connectivity methods, which assume that connectivity patterns remain constant over time, understanding the temporal dynamics of functional connectivity during rest may provide new insights into the dysfunction of the DMN in ASD. In this work, dynamic functional connectivity analysis based on sliding time window correlation was applied to the resting-state functional magnetic resonance imaging data of 28 young children with ASD (age range: 3-7 years) and 29 matched typically developing controls (TD group). In addition, k-means cluster analysis was performed to identify distinct temporal states based on the spatial similarity of each functional connectivity pattern. Compared with the TD group, young children with ASD showed decreased dynamic functional connectivity variance between the posterior cingulate cortex (PCC) and the right precentral gyrus, which is negatively correlated with social motivation and social relating. Cluster analysis revealed significant differences in functional connectivity patterns between the ASD and TD groups in discrete temporal states. Our findings reveal that atypical dynamic interactions between the PCC and sensorimotor cortex are associated with social deficits in ASD. Results also highlight the critical role of PCC in the social-cognitive deficits of ASD and support the concept that understanding the dynamic neural interactions among brain regions can provide insights into functional abnormalities in ASD. Autism Research 2018, 11: 1479-1493. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Social cognitive dysfunction in autism spectrum disorder (ASD) is associated with dysfunction of the default mode network (DMN), a set of brain areas involved in various domains of social processing. We found that decreases in the dynamic functional connectivity variance between the posterior cingulate cortex and the sensorimotor cortex are associated with deficits in social motivation and social relating in young children with ASD. This result suggests that aberrations in the DMN and its dynamic interactions with other networks contribute to atypical integration of information with respect to self and others.

A rapid cell-permeating turn-on probe for sensitive and selective detection of sulfite in living cells.

A rapid cell-permeating probe NJUXJ-1 was introduced for sensitive and selective detection of sulfite in living cells. It generated a turn-on response to sulfite with high sensitivity (detection limit 13.0 nM) and selectivity (at a physiological level) and low toxicity. The fluorescence of the detecting system was steady for a wide pH range (5-8) and a long period of time (over 12 h). The most attractive point, its rapid cell-permeating ability, made it suitable for bioimaging with a 2 min incubation time and shortened the whole detecting period (cell-permeation and reaction), and thus could decrease background interference. It offered a convenient approach for determining exogenous or endogenous sulfite levels in living cells and further applications.

Copper-Catalyzed Reductive Trifluoromethylation of Alkyl Iodides with Togni's Reagent.

This work illustrates a reductive cross-electrophile coupling protocol for trifluoromethylation of alkyl iodides under Cu-catalyzed/Ni-promoted reaction conditions. The use of diboron esters as the terminal reductant allows the effective generation of the alkyl-CF3 products with excellent functional group tolerance and broad substrate scope. A mechanism involving a reaction of alkyl-Cu with Togni's reagent was proposed.