Metagenomics insights into gentamicin degradation and the dynamic of antibiotic resistance genes during co-composting of the gentamicin myelial residues with addition of various organic wastes.

Increasing antibiotic mycelial residues (AMRs) and related antibiotic resistance genes (ARGs) pose a significant threat to ecosystems and public health. Composting is a crucial method for recycling AMRs. However, the variation in ARGs and gentamicin degradation in the composting process of gentamicin mycelial residues (GMRs) has received little attention on an actual industrial scale. This research investigated the metabolic pathways and functional genes on the gentamicin and ARGs removal during the co-composting of GMRs with addition of various organic wastes (rice chaff, mushroom residue, etc.) under various C/N ratios (15:1, 25:1, 35:1). The results showed that the removal efficiencies of gentamicin and the total ARGs were 98.23 % and 53.20 %, respectively, with the C/N ratio of 25:1. Moreover, metagenomics and LS-MS/MS analysis demonstrated that the acetylation was the primary pathway for gentamicin biodegradation and the corresponding degrading genes were the categories of aac(3) and aac(6'). However, the relative abundance of aminoglycoside resistance genes (AMGs) were increased after 60 days composting. The partial least squares path modeling analysis demonstrated that the AMG abundance was directly influenced by the predominant mobile gene elements intI1 (p < 0.05) which was closely related to the bacterial community composition. Therefore, the ecological environmental risks should be assessed in the future application of GMRs composting products.

Homogeneous Dearomative Hydrogenation with a Co/P4 N2 Catalyst: A Nucleophilic Approach.

Arene hydrogenation is the most straightforward method to prepare carbo- and heterocycles. However, the high resonance energy prevents aromatic substrates from hydrogenation. Herein the homogeneous, nucleophilic hydrogenation of less electron-rich arenes and heteroarenes is reported. The Co(P4 N2 )H species that has been demonstrated to be a strong hydride donor could deliver a hydride ion to the cyano (hetero)arene substrates. Deuterium labeling experiments supported a Michael-type reaction pathway. Theoretical analyses have been conducted to investigate the hydricity of the catalytically active CoH species and the electrophilicity of the arene substrates. An outlook for the synthesis of more challenging substituted benzenes was proposed based on the in silico modification of the CoH species.

Recent Developments and Aspects of Industrial Fluoroalkylation.

Fluoroalkylations have received increasing attention in the academic and industrial environment due to the particular properties of the active ingredients that are strongly influenced by fluoroalkyl substituents. The inherent difficulties of introducing a fluoroalkyl substituent into advanced intermediates has triggered the development of an enormous number of specialized reagents, which, however, are often not suitable for large scale applications. In contrast to this reagent based fluoroalkylation approach, the direct activation of industrially readily available fluoroalkyl halides could be more suitable for a large-scale process. In this way the dithionite initiated fluoroalkylation as well as newly developed catalytically activated fluoroalkylation protocols were considered for industrial large-scale applications.

Connectome-based model predicts episodic memory performance in individuals with subjective cognitive decline and amnestic mild cognitive impairment.

OBJECTIVE: To explore whether the whole brain resting-state functional connectivity (rs-FC) could predict episodic memory performance in individuals with subjective cognitive decline and amnestic mild cognitive impairment. METHOD: This study included 33 cognitive normal (CN), 26 subjective cognitive decline (SCD) and 27 amnestic mild cognitive impairment (aMCI) patients, and all the participants completed resting-state fMRI (rs-fMRI) scan and neuropsychological scale test data. Connectome-based predictive modeling (CPM) based on the rs-FC data was used to predict the auditory verbal learning test-delayed recall (AVLT-DR) scores, which measured episodic memory in individuals. Pearson correlation between each brain connection in the connectivity matrices and AVLT-DR scores was computed across the patients in predementia stages of Alzheimer's disease (AD). The Pearson correlation coefficient values separated into a positive network and a negative network. Predictive networks were then defined and employed by calculating positive and negative network strengths. CPM with leave-one-out cross-validation (LOOCV) was conducted to train linear models to respectively relate positive and negative network strengths to AVLT-DR scores in the training set. During the testing procedure, each left-out testing subject's strengths of positive and negative network was normalized using the parameters acquired during training procedure, and then the trained models were used to predict the testing participant's AVLT-DR score. RESULTS: The negative network predictive model tested LOOCV significantly predicted individual differences in episodic memory from rs-FC. Key nodes that brain regions contributed to the prediction model were mainly located in the prefrontal cortex, frontal cortex, parietal cortex and temporal lobe. CONCLUSION: Our findings demonstrated that rs-FC among multiple neural systems could predict episodic memory at the individual level.

Altered Regional Cerebral Blood Flow and Brain Function Across the Alzheimer's Disease Spectrum: A Potential Biomarker.

Objective: To investigate variation in the characteristics of regional cerebral blood flow (rCBF), brain activity, and intrinsic functional connectivity (FC) across the Alzheimer's disease spectrum (ADS). Methods: The study recruited 20 individuals in each of the following categories: Alzheimer's disease (AD), mild cognitive impairment (MCI), subjective cognitive decline (SCD), and healthy control (HC). All participants completed the 3.0T resting-state functional MRI (rs-fMRI) and arterial spin labeling scans in addition to neuropsychological tests. Additionally, the normalized CBF, regional homogeneity (ReHo), and amplitude of low-frequency fluctuation (ALFF) of individual subjects were compared in the ADS. Moreover, the changes in intrinsic FC were investigated across the ADS using the abnormal rCBF regions as seeds and behavioral correlations. Finally, a support-vector classifier model of machine learning was used to distinguish individuals with ADS from HC. Results: Compared to the HC subjects, patients with AD showed the poorest level of rCBF in the left precuneus (LPCUN) and right middle frontal gyrus (RMFG) among all participants. In addition, there was a significant decrease in the ALFF in the bilateral posterior cingulate cortex (PCC) and ReHo in the right PCC. Moreover, RMFG- and LPCUN-based FC analysis revealed that the altered FCs were primarily located in the posterior brain regions. Finally, a combination of altered rCBF, ALFF, and ReHo in posterior cingulate cortex/precuneus (PCC/PCUN) showed a better ability to differentiate ADS from HC, AD from SCD and MCI, but not MCI from SCD. Conclusions: The study demonstrated the significance of an altered rCBF and brain activity in the early stages of ADS. These findings, therefore, present a potential diagnostic neuroimaging-based biomarker in ADS. Additionally, the study provides a better understanding of the pathophysiology of AD.

Selective nickel-catalyzed fluoroalkylations of olefins.

Mild and selective nickel-catalyzed trifluoromethylation and perfluoroalkylation reactions of alkenes were developed to provide fluorinated olefins, including natural products, pharmaceuticals, and variety of synthetic building blocks in good to excellent yields (38 examples). Control experiments, kinetic measurements and in situ EPR studies reveal the importance of radical species and the formation of 1,2-adducts as intermediates.

Fatal and Rapid Progressive Isolated Cerebral Mucormycosis Involving the Bilateral Basal Ganglia: A Case Report.

Isolated cerebral mucormycosis is a clinical type of mucormycosis that is estimated to account for 8% of all mucormycosis cases. The clinical symptoms of isolated cerebral mucormycosis are elusive, and thus conventional techniques often lake sensitivity and specificity. Moreover, cultures are often negative, even when direct microscopy examination is positive. Although histopathology will probably remain the gold standard for the diagnosis of mucormycosis, obtaining a biopsy specimen is not always feasible in most vulnerable populations. Thus, molecular approaches are currently used as an advantageous assistant examination method to improve the early identification of the causative agent and subsequently guide therapy to improve the prognosis of patients. Here, we report a case of isolated cerebral mucormycosis caused by Rhizopus microspores in a healthy young adult that was identified using next-generation sequencing technology.

Synthesis of α,ß-unsaturated carbonyl compounds by carbonylation reactions.

α,ß-Unsaturated carbonyl compounds are key building blocks in organic chemistry. Their catalytic synthesis has received significant attention during the past decades. Among the known methodologies, carbonylation reactions represent an atom-efficient tool box to convert a variety of easily available substrates into valuable α,ß-unsaturated carbonylated products including aldehydes, ketones, esters, amides, and carboxylic acids. Herein, we summarize the most important achievements in this field with a special focus on results from the last decade.

Pd-catalyzed synthesis of α,ß-unsaturated ketones by carbonylation of vinyl triflates and nonaflates.

A general and highly chemoselective Pd-catalyzed protocol for the synthesis of α,ß-unsaturated ketones by carbonylation of vinyl triflates and nonaflates is presented. Applying the specific monophosphine ligand cataCXium® A, the synthesis of various vinyl ketones as well as carbonylated natural product derivatives proceeds in good yields.

Pd-Catalyzed Carbonylation of Vinyl Triflates To Afford α,ß-Unsaturated Aldehydes, Esters, and Amides under Mild Conditions.

An efficient and general protocol for the synthesis of α,ß-unsaturated aldehydes, esters, and amides via carbonylation of vinyl triflates including derivatives of camphor, ketoisophorone, verbenone, and pulegone was developed. Crucial for these transformations is the use of a specific palladium catalyst containing a pyridyl-substituted d tbpx-type ligand. This procedure also allows for an easy access of dicarbonylated products from the corresponding ketones.

A general and practical Ni-catalyzed C-H perfluoroalkylation of (hetero)arenes.

A direct perfluoroalkylation of (hetero)arenes using the air- and moisture-stable complex (dppf)Ni(o-tol)Cl was developed (23 examples). The novel procedure allows for the synthesis of various fluorinated products and tolerates sensitive functional groups including aldehydes, free amino groups and several heterocycles.

Pd-Catalyzed Cyanation of (Hetero)Aryl Halides by Using Biphosphine Ligands.

Tetraadamantylbiphosphine (TABP; L1), which showed superior activity in the palladium-catalyzed cyanation of 4-chloroanisole compared to standard phosphines, was synthesized as a new ligand. The generality of the new catalytic system was shown by the cyanation reaction of approximately 30 (hetero)aryl halides including hindered, electron-rich, and electron-poor aryl chlorides. These reactions constitute the first examples of using biphosphine ligands in Pd-catalyzed coupling reactions.