Electric field effects on neuronal input-output relationship by regulating NMDA spikes.

Evidence shows that the dendritic polarization induced by weak electrical field (EF) can affect the neuronal input-output function via modulating dendritic integration of AMPA synapses, indicating that the supralinear dendritic integration of NMDA synapses can also be influenced by dendritic polarization. However, it remains unknown how dendritic polarization affects NMDA-type dendritic integration, and then contributes to neuronal input-output relationship. Here, we used a computational model of pyramidal neuron with inhomogeneous extracellular potentials to characterize the relationship among EF, dendritic integration, and somatic output. Basing on singular perturbation we analyzed the subthreshold dynamics of membrane potentials in response to NMDA synapses, and found that the equilibrium mapping of a fast subsystem can characterize the asymptotic subthreshold input-output (sI/O) relationship for EF-regulated supralinear dendritic integration, allowing us to predict the tendency of EF-regulated dendritic integration by showing the variation of equilibrium mapping under EF stimulation. EF-induced depolarization at distal dendrites receiving synapses plays a crucial role in shifting the steep change of sI/O left by facilitating dendritic NMDA spike generation and in decreasing the plateau of sI/O via reducing driving force. And more effective EF modulation appears at sparsely activated NMDA receptors compared with clustered synaptic inputs. During the action potential (AP) generation, the respective contribution of EF-regulated dendritic integration and EF-induced somatic polarization was identified to show their synergetic or antagonistic effect on AP generation, depending on neuronal excitability. These results provided insight in understanding the modulation effect of EF on neuronal computation, which is important for optimizing noninvasive brain stimulation. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-022-09922-y.

State-dependent modulation of low-threshold-current-regulated dendritic Ca2+ response in thalamic reticular neurons with extracellular electric fields.

Deep brain stimulation (DBS) in thalamic reticular nucleus (TRN) neuron provides a novel treatment for drug-resistant epilepsy via the induced electrical field (EFs). However, the mechanisms underlying EF effects remain unclear. This paper investigated how EFs regulate low-threshold dendritic Ca2+ (dCa) response and thus contribute to the input-output relationship of TRN cell. Our results showed that EFs modulate firing modes differently in a neuronal state-dependent manner. At the depolarized state, EFs only regulate the spike timing of a somatic stimulus-evoked single action potential (AP) with less contribution in the regulation of dCa response but could induce the transition between a dendritic stimulus-evoked single AP and a tonic burst of APs via the moderate regulation of dCa response. At the hyperpolarized state, EFs have significant effects on the dCa response, which modulate the large dCa response-dependent burst discharge and even cause a transition from this type of burst discharge to a single AP with less dCa response. Moreover, EF effects on stimulation threshold of somatic spiking prominently depend on EF-regulated dCa responses and the onset time differences between the stimulus and EF give rise to the distinct effect in the EF regulation of dCa responses. Finally, the larger neuronal axial resistance tends to result in the dendritic stimulus-evoked dCa response independent of somatic state. Interestingly, in this case, the EF application could reproduce the similar somatic state-dependent dCa response to dendritic stimulus which occurs in the case of lower axial resistance. These results suggest that the influence of EF on neuronal activities depends on neuronal intrinsic properties, which provides insight into understanding how DBS in TRN neuron modulates epilepsy from the point of view of biophysics.

Prokaryote Distribution Patterns along a Dissolved Oxygen Gradient Section in the Tropical Pacific Ocean.

Oceanic oxygen levels are decreasing significantly in response to global climate change; however, the microbial diversity and ecological functional responses to dissolved oxygen (DO) in the open ocean are largely unknown. Here, we present prokaryotic distribution coupled with physical and biogeochemical variables and DO gradients from the surface to near the bottom of a water column along an approximately 12,000-km transect from 13° N to 18° S in the Tropical Pacific Ocean. Nitrate (11.42%), temperature (10.90%), pH (10.91%), silicate (9.34%), phosphate (4.25%), chlorophyll a (3.66%), DO (3.50%), and salinity (3.48%) significantly explained the microbial community variations in the studied area. A distinct microbial community composition broadly corresponding to the water masses formed vertically. Additionally, distinct ecotypes of Thaumarchaeota and Nitrospinae belonging to diverse phylogenetic clades that coincided with specific vertical niches were observed. Moreover, the correlation analysis revealed large-scale natural feedback in which chlorophyll a (organic matter) promoted Thaumarchaeotal biomass at depths that subsequently coupled with Nitrospina, produced and replenished nitrate for phytoplankton productivity at the surface. Low DO also favored Thaumarchaeota growth and fueled nitrate production.

Anti-Inflammatory and Proangiogenic Metabolites from the Hadal Trench-Derived Fungus Acremonium dichromosporum YP-213.

Four new compounds, including two ascochlorin-type meroterpenoids acremocholrins A (1) and B (2), one pyridone alkaloid acremopyridone A (7), and one cyclopentenone derivative acremoketene A (12), together with eight known compounds (3-6 and 8-11), were isolated and identified from the hadal trench-derived fungus Acremonium dichromosporum YP-213. Their structures were determined with a detailed spectroscopic analysis of NMR and MS data, NOE analysis, octant rule and quantum chemical calculations of ECD, and NMR (with DP4+ probability analysis). Among the compounds, 7 represent a novel scaffold derived from a pyridone alkaloid by cleavage of the C-16-C-17 bond following oxidation to give a ketone. Compounds 9, 11, and 12 showed potent in vivo anti-inflammatory activity in transgenic zebrafish, while compound 8 exhibited significant proangiogenic activity in transgenic zebrafish.

Comparative proteomics reveals the mechanism of cyclosporine production and mycelial growth in Tolypocladium inflatum affected by different carbon sources.

Cyclosporine A (CsA) is a secondary cyclopeptide metabolite produced by Tolypocladium inflatum that is widely used clinically as an immunosuppressant. CsA production and mycelial growth differed when T. inflatum was cultured in different carbon source media. During early fermentation, CsA was preferred to be produced in fructose medium, while the mycelium preferred to accumulate in sucrose medium. On the sixth day, the difference was most pronounced. In this study, high-throughput comparative proteomics methods were applied to analyze differences in protein expression of mycelial samples on day 6, revealing the proteins and mechanisms that positively regulate CsA production related to carbon metabolism. The differences included small molecule acid metabolism, lipid metabolism, organic catabolism, exocrine secretion, CsA substrate Bmt synthesis, and transcriptional regulation processes. The proteins involved in the regulation of mycelial growth related to carbon metabolism were also revealed and were associated with waste reoxidation processes or coenzyme metabolism, small molecule synthesis or metabolism, the stress response, genetic information or epigenetic changes, cell component assembly, cell wall integrity, membrane metabolism, vesicle transport, intramembrane localization, and the regulation of filamentous growth. This study provides a reliable reference for CsA production from high-efficiency fermentation. This study provides key information for obtaining more CsA high-yielding strains through metabolic engineering strategies.

Comparison of the Oncological and Functional Outcomes of Brachytherapy and Radical Prostatectomy for Localized Prostate Cancer.

Background and Objectives: To compare the oncological and functional outcomes of brachytherapy (BT) and radical prostatectomy (RP) in patients with localized prostate cancer (PCa). Materials and Methods: We retrospectively analyzed data from 557 patients with localized PCa who were treated with BT (n = 245) or RP (n = 312) at Northern Jiangsu People's Hospital between January 2012 and December 2017. Biochemical relapse-free survival (bRFS) and cancer-specific survival (CSS) were compared by treatment modality. Multivariate Cox regression analysis was used to evaluate bRFS. Health-related quality of life (HRQoL) was measured using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Results: The BT group was older and had a higher initial PSA (iPSA). The 5-year bRFS was 82.9% in the BT group versus 80.1% in the RP group (p = 0.570). The 5-year CSS was 96.4% in the BT group versus 96.8% in the RP group (p = 0.967). Based on multivariate Cox regression analysis, Gleason score ≥ 8 was the main independent prognostic factor for bRFS. Regarding the HRQoL, compared with the baseline, both treatments produced a significant decrease in different aspects of HRQoL at 3, 6, and 12 months after treatment. Patients in the BT group had lower HRQoL with regard to urinary irritation/obstruction and bowel function or bother, while patients in the RP group had lower HRQoL concerning urinary incontinence and sexual function or bother. There was no significant difference in HRQoL aspects between the two groups after follow-up for 2 years compared with the baseline. Conclusions: BT provides equivalent oncological control outcomes in terms of bRFS and CSS for patients with localized PCa compared with RP. Gleason score ≥ 8 was the main independent prognostic factor for bRFS. BT had better HRQoL compared with RP, except for urinary irritation/obstruction and bowel function or bother, but returned to baseline after 2 years.

Pro-angiogenic New Chloro-Azaphilone Derivatives From the Hadal Trench-Derived Fungus Chaetomium globosum YP-106.

Five new chloro-azaphilones, chaetofanixins A-E (1-5), and five known analogs (6-10) were isolated and identified from the hadal trench-derived fungus Chaetomium globosum YP-106. The structure of chaetofanixin E (5) is unique and interesting, bearing a highly rigid 6/6/5/3/5 penta-cyclic ring system, which is first encountered in natural products. The structures of these compounds, including absolute configurations, were determined based on the spectroscopic analysis, electronic circular dichroism (ECD) calculations, and analysis of biogenetic origins. Compounds 1-7 significantly promoted angiogenesis in a dose-dependent manner, and thus, these compounds might be used as promising molecules for the development of natural cardiovascular disease agents.

Sulfur-Containing Compounds from Endophytic Fungi: Sources, Structures and Bioactivities.

Endophytic fungi have attracted increasing attention as an under-explored source for the discovery and development of structurally and functionally diverse secondary metabolites. These microorganisms colonize their hosts, primarily plants, and demonstrate diverse ecological distribution. Among endophytic fungal natural products, sulfur-containing compounds feature one or more sulfur atoms and possess a range of bioactivities, e.g., cytotoxicity and antimicrobial activities. These natural products mainly belong to the classes of polyketides, nonribosomal peptides, terpenoids, and hybrids. Here, we reviewed the fungal producers, plant sources, chemical structures, and bioactivities of 143 new sulfur-containing compounds that were reported from 1985 to March 2022.

Methylene-bridged dimeric natural products involving one-carbon unit in biosynthesis.

Covering: up to February 2022Naturally occurring dimeric molecules attract considerable attention from both chemists and biologists. The methylene-bridged dimers with one-carbon (C1) unit in biosynthesis, which are a small class of structurally diverse natural products, are found in plants, microorganisms, and marine bryozoan. Some individual dimers showed more significant biological activities than the corresponding monomers. Focusing on these dimers with a methylene linker, we here reviewed associated progress in the isolation, biological activity, chemical synthesis, and the proposed dimerization mechanism. The structural characteristics of the monomeric substrates are summarized, which indicated that most of these dimers might be formed through nonenzymatic dimerization involving a strong electrophilic C1 unit such as formaldehyde. This kind of dimerization is an effective synthetic strategy for the discovery of new biologically active compounds.

Evaluation of Pembrolizumab Monotherapy Efficacy in Advanced Non-Small-Cell Lung Cancer by Serial Monitoring of Circulating Tumor DNA Using Next-Generation Sequencing.

INTRODUCTION: Pembrolizumab is widely used in advanced non-small-cell lung cancer (NSCLC) patients with positive programmed death-ligand 1 (PD-L1). However, efficacy evaluation along treatment by serial monitoring of circulating tumor DNA (ctDNA) using next-generation sequencing remained to be well studied. METHODS: Nine PD-L1 positive advanced NSCLC patients were prospectively enrolled and received pembrolizumab monotherapy. Pretreatment tissue and/or plasma samples were collected as baseline reference. Serial plasma samples were collected after 3 and 6 weeks of treatment as well as at disease progression. All samples underwent targeted next-generation sequencing. RESULTS: The median progression-free survival (mPFS) and median overall survival (mOS) were 4.43 and 25.53 months, respectively. In total, 3 patients achieved partial response (PR) or stable disease (SD) for more than 6 months and were thus classified into the durable clinical benefit (DCB) group, whereas the rest 6 were grouped as nondurable benefit (NDB) patients. Molecular profiling of baseline samples revealed that TP53 and APC were the 2 most frequently mutated genes in all patients, whereas POT1 and SETD2 mutations were enriched in DCB and NDB groups, respectively. Higher tumor mutational burden (TMB) was observed in DCB patients than NDB group. During serial ctDNA monitoring, 2 DCB patients showed a dramatic ctDNA reduction while 75% of NDB patients' ctDNA concentration increased at week 6. Several acquired mutations might contribute to the pembrolizumab resistance, including CDKN2A frameshift and MITF nonsense mutations. CONCLUSIONS: Genomic profiling of peripheral blood samples can be applied to dynamically monitor disease progression. The reduction in ctDNA concentration during treatment implied DCBs.

New lanostane-type triterpenoids with proangiogenic activity from the fruiting body of Ganoderma applanatum.

Two new lanostane-type triterpenoids, ganoderenicfys A (1) and B (2), together with six related known terpenoids (3-8), were isolated and identified from the fruiting body of Ganoderma applanatum. The structures of these compounds were established on the basis of detailed interpretation of their NMR and HRESIMS data. The absolute configurations of 1 and 2 were determined by quantum chemical electronic circular dichroism (ECD) calculations. All of the isolated compounds were evaluated for their proangiogenic activities in a transgenic fluorescent zebrafish model. Compounds 1-6 displayed dose-dependently proangiogenic activity in a PTK787-induced vascular injury zebrafish model, while compounds 1, 2 and 4 significantly promoted the angiogenesis. This is the first report for proangiogenic activities of lanostane-type triterpenoids.

Complete genome sequence of a nitrate reducing bacteria, Algoriphagus sp. Y33 isolated from the water of the Indian Ocean.

Algoriphagus sp. Y33, is a nitrate-reducing bacterium isolated from the water of Indian Ocean. Here, we present the complete genome sequence of strain Y33. The genome has one circular chromosome of 6,378,979 bp, with an average GC content of 41.86%, and 5757 coding sequences. According to the annotation analysis, strain Y33 encodes 32 proteins related to nitrogen metabolism. To our knowledge, this is the first report of Algoriphagus sp. isolated from the Indian Ocean with the capacity of nitrate reduction, which will provide insights into regulatory mechanisms of nitrate uptake by heterotrophic bacteria and the global nitrogen cycling.

Asymptotic Input-Output Relationship Predicts Electric Field Effect on Sublinear Dendritic Integration of AMPA Synapses.

An extracellular electric field (EF) induces transmembrane polarizations on extremely inhomogeneous spaces. Evidence shows that EF-induced somatic polarization in pyramidal cells can modulate the neuronal input-output (I/O) function. However, it remains unclear whether and how dendritic polarization participates in the dendritic integration and contributes to the neuronal I/O function. To this end, we built a computational model of a simplified pyramidal cell with multi-dendritic tufts, one dendritic trunk, and one soma to describe the interactions among EF, dendritic integration, and somatic output, in which the EFs were modeled by inserting inhomogeneous extracellular potentials. We aimed to establish the underlying relationship between dendritic polarization and dendritic integration by analyzing the dynamics of subthreshold membrane potentials in response to AMPA synapses in the presence of constant EFs. The model-based singular perturbation analysis showed that the equilibrium mapping of a fast subsystem can serve as the asymptotic subthreshold I/O relationship for sublinear dendritic integration. This allows us to predict the tendency of EF-mediated dendritic integration by showing how EF changes modify equilibrium mapping. EF-induced hyperpolarization of distal dendrites receiving synapses inputs was found to play a key role in facilitating the AMPA receptor-evoked excitatory postsynaptic potential (EPSP) by enhancing the driving force of synaptic inputs. A significantly higher efficacy of EF modulation effect on global AMPA-type dendritic integration was found compared with local AMPA-type dendritic integration. During the generation of an action potential (AP), the relative contribution of EF-modulated dendritic integration and EF-induced somatic polarization was determined to show their collaboration in promoting or inhibiting the somatic excitability, depending on the EF polarity. These findings are crucial for understanding the EF modulation effect on neuronal computation, which provides insight into the modulation mechanism of noninvasive brain modulation.

The Effect of Hippocampal Avoidance Whole Brain Radiotherapy on the Preservation of Long-Term Neurocognitive Function in Non-Small Cell Lung Cancer Patients With Brain Metastasis.

Whole-brain radiotherapy (WBRT) is the mainstay of therapy in treating cancer patients with brain metastases, but unfortunately, it might also lead to decline in neurocognitive function. This study aims to investigate the preservation of long-term neurocognitive function in patients after hippocampal avoidance whole-brain radiotherapy (HA-WBRT). Retrospectively, 47 patients diagnosed with brain metastases of non-small cell lung cancer (NSCLC) between 2015-01-01 and 2017-12-31 at the Department of Oncology, XXX Hospital were selected and divided into 2 groups. Group A (n = 27) received HA-WBRT, whereas group B (n = 20) received WBRT. Neurocognitive function was analyzed at baseline and at 3, 6, 9, 12 and 24 months after radiotherapy, using Mine-Mental State Examination (MMSE) scales and Montreal Cognitive Assessment (MoCA) scales. The OS, PFS and tumor recurrence sites were also analyzed. When evaluated at 12 and 24 months after radiotherapy, the cognitive function scores of the hippocampal avoidance group were significantly higher than those of the non-hippocampal avoidance group (P < 0.001). In terms of patient survival, there was no significant difference in OS (P = 0.2) and PFS (P = 0.18) between these 2 groups. Fourteen patients in group A and 12 patients in group B had brain tumor recurrence after radiation, only one patient in group A occurred within 5 mm from the edge of the hippocampus (P > 0.05). In conclusion, HA-WBRT might have a protective effect on long-term neurocognitive function and did not affect patient survival.

A Combination of RNA-Seq Analysis and Use of TCGA Database for Determining the Molecular Mechanism and Identifying Potential Drugs for GJB1 in Ovarian Cancer.

BACKGROUND: There has been increasing evidence for the vital role played by gap junction protein beta-1 (GJB1) in ovarian cancer (OC) and for the possibility of this protein serving as a therapeutic target. However, the detailed mechanism of GJB1 in OC has not yet been clearly determined. The current study aimed to establish the molecular mechanisms of the involvement of GJB1 in OC and to further predict potential drugs targeting this protein. METHODS: To better understand the molecular mechanisms of the involvement of GJB1 in OC, RNA-Seq transcriptome sequencing was performed. Then, we carried out an RNA-Seq analysis to determine the genes differentially co-expressed with GJB1. Subsequently, we carried out bioinformation methods to study the upstream regulatory transcriptional factor (TF) of GJB1. Further, the binding of FOXA1 and GJB1 promoter was tested using ChIP-qPCR. Moreover, we performed pathway enrichment to identify the downstream regulatory mechanisms of GJB1. Furthermore, potential drugs targeting GJB1 were screened using AutoDock 4.2. RESULTS: We constructed the transcriptional factor FOXA1 regulatory network based on the AnimalTFDB, JASPAR, RNA-Seq, TCGA cohort and ChIP-qPCR to study the upstream regulation of GJB1. In addition, two key pathways for the involvement of GJB1 in OC-namely the "ECM-receptor interaction" and "focal adhesion" KEGG pathways-were identified. Furthermore, ZINC000005552022 was found in a screening to be a potentially promising drug targeting GJB1. CONCLUSION: Our study results suggested that the transcriptional factor FOXA1 regulates the involvement of GJB1 in OC through ECM-receptor interaction and focal adhesion KEGG pathways, and that ZINC000005552022 may have promising potential as a drug targeting GJB1; this finding might be used to help accelerate drug development and improve the outcomes for patients with OC.

Targeting of FK506 binding protein 5 by miR-203 affects the progression of breast cancer via regulating the fatty acid degradation pathway and potential drug-repurposing.

Increasing number of studies have suggested that microRNA (miR)-203 is a potential prognostic marker for breast cancer. However, the specific molecular mechanism underlying the effects of miR-203 remains unknown. The present study aimed to explore the molecular target and underlying mechanisms of action of miR-203 in breast cancer via bioinformatics analysis and cellular assays, such as wound healing assay and western blotting. In the present study, 17 candidate target genes of miR-203 were identified in the downregulated differentially expressed genes from Affymetrix microarray and TargetScan 7.2 database. Subsequently, FK506 binding protein 5 (FKBP5) was considered as the miR-203 target by 3 different hub gene analysis methods (EcCentricity, Betweenness and Stress). FKBP5 protein expression was significantly downregulated in SUM159 cells transfected with miR-203 mimics compared with SUM159 cells transfected with miR-203 negative control (NC) in western blot analysis. High expression of FKBP5 was associated with poor prognosis in breast cancer based on the results obtained from the Kaplan-Meier Plotter database. In addition, the wound healing assay indicated that the inhibition of migration due to miR-203 overexpression in SUM159 cells was reversed by FKBP5 overexpression. These results suggested that miR-203 may directly target FKBP5. In addition, Gene Set Enrichment Analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that miR-203 might play a role in breast cancer via the 'fatty acid degradation' KEGG pathway. Notably, the levels of fatty acids were significantly reduced in SUM159 cells transfected with miR-203 mimics compared with SUM159 cells transfected with miR-203 NC when assessed by the fatty acid content assay. Finally, virtual screening analysis revealed that ZINC000003944422 may be a potential inhibitor of FKBP5. In summary, the present study demonstrated that miR-203 may directly target FKBP5 in breast cancer via fatty acid degradation and potential drugs, hence providing a novel treatment approach for breast cancer.

Metabolic Cost of Dendritic Ca2+ Action Potentials in Layer 5 Pyramidal Neurons.

Pyramidal neurons consume most signaling-related energy to generate action potentials (APs) and perform synaptic integration. Dendritic Ca2+ spike is an important integration mechanism for coupling inputs from different cortical layers. Our objective was to quantify the metabolic energy associated with the generation of Ca2+ APs in the dendrites. We used morphology-based computational models to simulate the dendritic Ca2+ spikes in layer 5 pyramidal neurons. We calculated the energy cost by converting Ca2+ influx into the number of ATP required to restore and maintain the homeostasis of intracellular Ca2+ concentrations. We quantified the effects of synaptic inputs, dendritic voltage, back-propagating Na+ spikes, and Ca2+ inactivation on Ca2+ spike cost. We showed that much more ATP molecules were required for reversing Ca2+ influx in the dendrites than for Na+ ion pumping in the soma during a Ca2+ AP. Increasing synaptic input increased the rate of dendritic depolarization and underlying Ca2+ influx, resulting in higher ATP consumption. Depolarizing dendritic voltage resulted in the inactivation of Ca2+ channels and reduced the ATP cost, while dendritic hyperpolarization increased the spike cost by de-inactivating Ca2+ channels. A back-propagating Na+ AP initiated in the soma increased Ca2+ spike cost in the apical dendrite when it coincided with a synaptic input within a time window of several milliseconds. Increasing Ca2+ inactivation rate reduced Ca2+ spike cost, while slowing Ca2+ inactivation increased the spike cost. The results revealed that the energy demand of a Ca2+ AP was dynamically dependent on the state of dendritic activity. These findings were important for predicting the energy budget for signaling in pyramidal cells, interpreting functional imaging data, and designing energy-efficient neuromorphic devices.

Cloning and heterologous expression of a novel halo/alkali-stable multi-domain xylanase (XylM18) from a marine bacterium Marinimicrobium sp. strain LS-A18.

Halophilic bacteria are good bioresources for halotolerant alkaline enzymes. A multi-domain high-molecular-weight endo-ß-1,4-xylanase gene, xylM18, was cloned from a halophilic marine bacterium Marinimicrobium sp. LS-A18. XylM18 is different from any of the functionally reported xylanases. It has a glycosyl hydrolase (GH) 43 domain, a GH10 domain, and two serine-rich linkers, representing a novel family. The gene, encoding 1022 residues, was cloned and heterologously expressed in Escherichia coli BL21(DE3) cells. Purified XylM18 was proved to be a xylanase. It showed diminished activity without salt and showed activity with a broad NaCl range from 0.2 to 25% (w/v). NaCl can increase the optimal temperature from 30 °C (0% NaCl) to 50 °C (10% NaCl). The purified XylM18 was active between pH 6.0 and 10.0 and was optimally active at pH 7.0. The xylanase activities were basically unchanged at a NaCl concentration range from 10 to 20% or pH from 7 to 10 after 24 h incubation. The apparent Km and Vmax values of XylM18 for xylan were 2.76 mg/mL and 60.0 U/mg, respectively. The GH10 domain of this enzyme, XylM18-GH10, was expressed and characterized. XylM18-GH10 also showed xylanase activity and maintained halo-stable property. The apparent Km and Vmax values of XylM18-GH10 for xylan were 1.60 mg/mL and 130.1 U/mg, respectively. Other domains of XylM18 showed no xylanase activity. In summary, XylM18 is a halo-tolerant and alkali-stable endoxylanase which is a suitable candidate for xylan biodegradation in high-salt and alkali conditions. To our knowledge, this is the first report of a multidomain high-molecular-weight xylanase.

Sekgranaticin, a SEK34b-Granaticin Hybrid Polyketide from Streptomyces sp. 166.

Sekgranaticin (1), a novel hybrid polyketide with a complex 6/6/6/6/6/6/6 7-ring system, was isolated together with granaticins A (2) and B (3) and methyl granaticinate (4) from the culture broth of Streptomyces sp. 166#. Its structure was elucidated by spectroscopic analysis. The absolute configuration was determined on the basis of the calculated 13C NMR and electronic circular dichroism data. Compounds 1-4 exhibited potent cytotoxicity against cancer cell lines MCF-7, A549, P6C, and HCT-116 with IC50 values of 0.02-6.77 µM. The biosynthetic pathway of sekgranaticin (1) was proposed.

Circumdatin-Aspyrone Conjugates from the Coral-Associated Aspergillus ochraceus LCJ11-102.

Ochrazepines A-D (1-4), four new conjugates dimerized from 2-hydroxycircumdatin C (5) and aspyrone (6) by a nucleophilic addition to epoxide, were isolated from the fermentation broth of the coral-associated Aspergillus ochraceus strain LCJ11-102. Their structures including absolute configurations were determined based on spectroscopic analysis and chemical methods. Compounds 1-4 were also obtained by the semisynthesis from a nucleophilic addition of 2-hydroxycircumdatin C (5) to aspyrone (6). New compound 1 exhibited cytotoxic activity against 10 human cancer cell lines while new compounds 2 and 4 selectively inhibited U251 (human glioblastoma cell line) and compound 3 was active against A673 (human rhabdomyoma cell line), U87 (human glioblastoma cell line), and Hep3B (human liver cancer cell line) with IC50 (half maximal inhibitory concentration) values of 2.5-11.3 µM among 26 tested human cancer cell lines.