Superposition model for analyzing the dynamic ground subsidence in mining area of thick loose layer

The dynamic ground subsidence due to underground mining is a complicated time-dependent and rate- dependent process. Based. on the theory of rock rheology and probability integral method, this study developed the superposltlOn model for the prediction and analysis of the ground dynamic subsidence in mining area of thick !oose layer. The model consists of two parts （the prediction of overlying bedrock and the prediction of thick loose layer）. The overlying bedrock is regarded as visco-elastic beam, of which the dynamic subsidence is predicted by the Kelvin visco-elastic rheological model. The thick loose layer is regarded as random medium, and the ground dynamic subsidence, is predicted by the probability integral model. At last, the two prediction models are vertically stacked in the same coordinate system, and the bedrock dynamic subsidence is regarded as a variable mining thickness input into the prediction model of ground dynamic subsidence. The prediction results obtained were compared w^th actual movement and deformation data from Zhao I and Zhao II mine, central China. The agreement of the prediction results with the. field measurements.show that the superposition model （SM） is more satisfactory and the formulae obtained are more effective than the classical single probability Integral model（SPIM）, and thus can be effectively used for predicting the ground dynamic subsidence in mining area of thick loose layer.

Immunosuppressant mycophenolic acid biosynthesis employs a new globin-like enzyme for prenyl side chain cleavage

Mycophenolic acid(MPA,1)and its derivatives are first-line immunosuppressants used in organ transplantation and for treating autoimmune diseases.Despite chemical synthetic achievements,the biosynthetic formation of a seven-carbon carboxylic acid pharmacophore side chain of 1,especially the processes involving the cleavage of the prenyl side chain between DHMP(4)and DMMPA(5),remains unknown.In this work,we identified a membrane-bound prenyltransferase,PgMpaA,that transfers FPP to 4 to yield FDHMP(6).Compound 6 undergoes the first cleavage step via a new globin-like enzyme PgMpaB to form a cryptic intermediate 12.Heterologous expression of PgMpa genes in Aspergillus nidulans demonstrates that the second cleavage step(from 12 to 5)of 1 is a PgMpa clusterindependent process in vivo.Our results,especially the discovery of the broad tolerance of substrates recognized by PgMpaB,set up a strategy for the formation of"pseudo-isopentenyl"natural products using fungal globin-like enzymes.

Linear polyketides produced by co-culture of Penicillium crustosum and Penicillium fellutanum

Two new polyketides, penifellutins A (1) and B (2), possessing a 22 carbon linear skeleton, were isolated from a co-culture of the deep-sea-derived fungi Penicillium crustosum PRB-2 and Penicillium fellutanum HDN14-323. Meanwhile, two esterification products of 1, penifellutins C (3) and D (4), were obtained because compound 1 could be esterified spontaneously when stored in methanol. Their configurations were difficult to determine because of chiral central crowdedness, structural flexibility and instability. As such, we solved this issue by comprehensively using Mo2(OAc)4-based CD experiments, density functional theory calculation of 13C NMR, DP4 + probability analysis and many chemical reactions, including making acetonide derivative, Mosher’s method, PGME method, etc. Compounds 1 and 2 show obvious inhibitory activity on the liver hyperplasia of zebrafish larvae at a concentration of 10 μmol/L, while 3 and 4 show no activity, indicating that two carboxyls in the structure are important active sites.

Bioinspired synthesis of cochlearol B and ganocin A

Described here is a divergent,biosynthetically inspired synthesis of cochlearol B and ganocin A.Key steps of the synthesis include the chromene unit construction through a biomimetic acid-catalyzed[4+2]ring cyclization.A photochemical[2+2]cycloaddition was featured to construct the cyclobutane core of cochlearol B.Different skeletal rearrangements of cochlearol B afforded ganocin A,that one of them was Lewis acid mediated epoxide rearrangement and another was DDQ induced cyclobutane formed tetrahydrofuran ring.The described syntheses not only achieved these natural products in an efficient manner,but also provided insight into the biosynthetic relationship between the two different skeletons.

Inhibition of MALT1 paracaspase activity improves lesion recovery following spinal cord injury

Spinal cord injury(SCI) is a devastating traumatic injury that causes persistent, severe motor and sensory dysfunction. Immune responses are involved in functional recovery after SCI. Mucosa-associated lymphoid tissue lymphoma translocation 1(MALT1) has been shown to regulate the survival and differentiation of immune cells and to play a critical role in many diseases, but its function in lesion recovery after SCI remains unclear. In this paper, we generated KI(knock in) mice with a point mutation(C472 G) in the active center of MALT1 and found that the KI mice exhibited improved functional recovery after SCI.Fewer macrophages were recruited to the injury site in KI mice and these macrophages differentiated into anti-inflammatory macrophages. Moreover, macrophages from KI mice exhibited reduced phosphorylation of p65, which in turn resulted in decreased SOCS3 expression and increased pSTAT6 levels.Similar results were obtained upon inhibition of MALT1 paracaspase with the small molecule inhibitor‘‘MI-2' or the more specific inhibitor ‘‘MLT-827'. In patients with SCI, peripheral blood mononuclear cells(PBMC) displayed increased MALT1 paracaspase. Human macrophages showed reduced proinflammatory and increased anti-inflammatory characteristics following the inhibition of MALT1 paracaspase. These findings suggest that inhibition of MALT1 paracaspase activity in the clinic may improve lesion recovery in subjects with SCI.

Peptaibols:Diversity, bioactivity, and biosynthesis

Peptaibols are a large family of linear,amphipathic polypeptides consisting of 5-20 amino acid residues gener-ated from the fungal nonribosomal peptide synthetase(NRPS)pathway.With a relatively high content of non-proteinogenic amino acids such as𝛼-aminoisobutyrate(Aib)and isovaline(Iva)in the skeleton,peptaibols exhibit a wide range of biological activities,including anti-microbial,cytotoxic,and neuroleptic effects.With five peptai-bols brought to market for use as biocontrol agents,this class of peptides has received increasing attention from both biochemists and pharmacologists.In this review,we summarized the progress made in structural character-ization,elucidation of biosynthetic pathways,and investigation of biosynthesis elucidation and bioactivities,to promote further efforts to develop peptaibols as pharmaceuticals.

Structural diversity and biological activity of natural p-terphenyls

p-Terphenyls are aromatic compounds consisting of a central benzene ring substituted with two phenyl groups,and they are mainly isolated from terrestrial and marine organisms.The central ring of p-Terphenyls is usually modified into more oxidized forms,e.g.,para quinone and phenols.In some cases,additional ring systems were observed on the terphenyl-type core structure or between two benzene moieties.p-Terphenyls have been reported to have cytotoxic,antimicrobial,antioxidant andα-glucosidase inhibitory effects.In this review,we will mainly summarize the structural diversity and biological activity of naturally occurring p-Terphenyls referring to the research works published before.

sea-derived fungus Acremonium sp.HDN16-126

Acremonium species are prolific producers of therapeutic molecules which include the widely used beta-lactam antibiotic,cephalosporin.In light of their significant medical value,an efficient gene disruption method is required for the physiological and biochemical studies on this genus of fungi.However,the number of selection markers that can be used for gene targeting is limited,which constrain the genetic analysis of multiple functional genes.In this study,we established a uridine auxotrophy based marker recycling system which achieves scarless gene deletion,and allows the use of the same selection marker in successive transformations in a deep seaderived fungus Acremonium sp.HDN16-126.We identified one homologue of Acremonium chrysogenum pyrG(also as a homologous gene of the yeast URA3)from HDN16-126,designated as pyrG-A1,which can be used as a selection marker on uridine free medium.We then removed pyrG-A1 from HDN16-126 genome via homologous recombination(HR)on MM medium with 5-fluoroortic acid(5-FOA),a chemical that can be converted into a toxin of 5-flurouracil by pyrG-A1 activity,thus generating the HDN16-126-△pyrG mutant strain which showed auxotrophy for uridine but insensitivity to 5-FOA and enabled the use of exogenous pyrG gene as both positive and negative selection marker to achieve the scarless deletion of target DNA fragments.We further applied this marker recycling system to successfully disrupt two target genes pepL(encodes a putative 2OG-Fe(Ⅱ)dioxygenase)and pepM(encodes a putative aldolase)identified from HDN16-126 genome,which are proposed to be functional genes related to 2-aminoisobutyric acid metabolism in fungi.This work is the first application of uridine auxotrophy based scarless gene deletion method in Acremonium species and shows promising potential in assisting sequential genetic analysis of filamentous fungi.