LncPCD: a manually curated database of experimentally supported associations between lncRNA-mediated programmed cell death and diseases.

Programmed cell death (PCD) refers to controlled cell death that is conducted to keep the internal environment stable. Long noncoding RNAs (lncRNAs) participate in the progression of PCD in a variety of diseases. However, no specialized online repository is available to collect and store the associations between lncRNA-mediated PCD and diseases. Here, we developed LncPCD, a comprehensive database that provides information on experimentally supported associations of lncRNA-mediated PCD with diseases. The current version of LncPCD documents 6666 associations between five common types of PCD (apoptosis, autophagy, ferroptosis, necroptosis and pyroptosis) and 1222 lncRNAs in 331 diseases. We also manually curated a wealth of information: (1) 7 important lncRNA regulatory mechanisms, (2) 310 PCD-associated cell types in three species, (3) detailed information on lncRNA subcellular locations and (4) clinical applications for lncRNA-mediated PCD in diseases. Additionally, 10 single-cell sequencing datasets were integrated into LncPCD to characterize the dynamics of lncRNAs in diseases. Overall, LncPCD is an extremely useful resource for understanding the functions and mechanisms of lncRNA-mediated PCD in diseases. Database URL:  http://spare4.hospital.studio:9000/lncPCD/Home.jsp.

An integrated method for studying the biodegradation of benzo[a]pyrene by Citrobacter sp. HJS-1 and interaction mechanism based on the structural model of the initial dioxygenase.

A bacterial strain Citrobacter sp. HJS-1 was discovered from the sludge in a drainage canal of a coal mine. Firstly, its biodegradation capacity for benzo[a]pyrene (BaP) was detected under different concentrations. The results proved that the strain possessed excellent biodegradation capacity for BaP with high-efficiency degradation rates ranging from 78.9 to 86.8%. The highest degradation rate was observed in the low-concentration sample, and the high-concentration BaP had a slight influence on the biodegradation capacity due to the potential toxicity of BaP and its oxygen-containing derivatives. Meanwhile, the degradation test for the other five aromatic hydrocarbons (2- to 4-ring) proved that the strain had a comprehensive degradation potential. To clarify the biodegradation mechanism of BaP, a dioxygenase structure was constructed by homology modeling. Then, the interactions between dioxygenase and BaP were researched by molecular simulation. Combined with the identification of the vital BaP-cis-7,8-dihydrodiol intermediate and the interaction analysis, the initial oxidation mode and the binding site of BaP were revealed in the dioxygenase. Taken together, this study has offered a way to understand the biodegradation process of BaP and its interaction mechanism based on experimental and theoretical analysis.

Biotransformation of benzo[a]pyrene by Pannonibacter sp. JPA3 and the degradation mechanism through the initially oxidized benzo[a]pyrene-4,5-dihydrodiol to downstream metabolites.

Owing to its adverse effects on the environment and human health, benzo[a]pyrene (BaP) has attracted considerable attention and has been used as a model compound in ecotoxicology. In this study, Pannonibacter sp. JPA3 as a BaP-degrading strain was isolated from the production water of an oil well. The strain could remove 80% of BaP at an initial concentration of 100 mg L-1 after 35 d culture. The BaP-4,5-dihydrodiol, BaP-4,5-epoxide, 5-hydroxychrysene, and 2-hydroxy-1-naphthoic acid metabolites were identified in the biodegradation process. Simultaneously, the gene sequence coding for dioxygenase in the strain was amplified and a dioxygenase model was built by homology modeling. Combined with the identification of the metabolites, the interaction mechanism of BaP with dioxygenase was investigated using molecular docking. It was assumed that BaP was initially oxidized at the C4-C5 positions in the active cavity of dioxygenase. Moreover, a hypothesis for the progressive degradation mechanism of BaP by this strain was proposed via the identification of the downstream metabolites. In conclusion, our study provided an efficient BaP degrader and a comprehensive reference for the study of the degradation mechanism in terms of the degrading metabolites and theoretical research at the molecular level.

Sulfur disproportionation tendencies in a sulfur packed bed reactor for perchlorate bio-autotrophic reduction at different temperatures and spatial distribution of microbial communities.

This study investigates the sulfur (S) disproportionation tendencies in a sulfur packed bed reactor for perchlorate bio-autotrophic reduction at different temperatures. The reactor was operated with over 99% efficiency for 21.00 ±â€¯1.40 mg L-1 perchlorate removal when the hydraulic retention time (HRT) ranged from 12.00 h to 0.75 h at 27 ±â€¯2 °C. When HRT was controlled at 1.00 h, the perchlorate removal efficiency was only 8 ±â€¯1% as the temperature dropped to 6 ±â€¯1 °C. The half-order model fit both perchlorate removal and S disproportionation reaction well. Compared with S disproportionation, the decrease of temperature had a greater influence on perchlorate reduction. As the temperature dropped from 27 ±â€¯2 °C to 6 ±â€¯1 °C, the 1/2K1/2v,R for perchlorate reduction decreased from 7.37 mg1/2 L-1/2 h-1 to 0.19 mg1/2 L-1/2 h-1. Meanwhile, the 1/2K1/2v,S for S disproportionation decreased from 3.04 mg1/2 L-1/2 h-1 to 1.96 mg1/2 L-1/2 h-1. The reaction activation energy of perchlorate reduction and S disproportionation was 120.28 kJ mol-1 and 13.44 kJ mol-1, respectively. The S disproportionation reaction proceeded remarkably at the beginning of the reduction, a longer HRT and higher temperature promoted S disproportionation, resulting in excessive sulfate generation and alkalinity consumption. Besides, the spatial distribution of the microbial communities and the dominant bacteria function under different HRTs was analyzed using high-throughput sequencing.

Fluoranthene degradation and binding mechanism study based on the active-site structure of ring-hydroxylating dioxygenase in Microbacterium paraoxydans JPM1.

In this study, a gram-positive fluoranthene-degrading bacterial strain was isolated from crude oil in Dagang Oilfield and identified as Microbacterium paraoxydans JPM1 by the analysis of 16S rDNA sequence. After 25 days of incubation, the strain JPM1 could degrade 91.78 % of the initial amount of fluoranthene. Moreover, four metabolites 9-fluorenone-1-carboxylic acid, 9-fluorenone, phthalic acid, and benzoic acid were detected in the culture solution. The gene sequence encoding the aromatic-ring-hydroxylating dioxygenase was amplified in the strain JPM1 by PCR. Based on the translated protein sequence, a homology modeling method was applied to build the crystal structure of dioxygenase. Subsequently, the interaction mechanism between fluoranthene and the active site of dioxygenase was simulated and analyzed by molecular docking. Consequently, a feasible degrading pathway of fluoranthene in the strain JPM1 was proposed based on the metabolites and the interaction analyses. Additionally, the thermodynamic analysis showed that the strain JPM1 had high tolerance for fluoranthene, and the influence of fluoranthene for the bacterial growth activity was negligible under 100 to 400 mg L-1 concentrations. Taken together, this study indicates that the strain JPM1 has high potential for further study in bioremediation of polycyclic aromatic hydrocarbon (PAH)-contaminated sites.

Biodegradation of pyrene by pseudomonas sp. JPN2 and its initial degrading mechanism study by combining the catabolic nahAc gene and structure-based analyses.

In this study, a pyrene-degrading bacterial strain Pseudomonas sp. JPN2 was isolated from crude oil in Dagang Oilfield, China. The degrading percent of the strain JPN2 to pyrene was increased with the extension of culture time and achieved a maximum of 82.88% after 25 d culture. Meanwhile, four metabolites 4,5-dihydroxy-4,5-dihydropyrene, 4-phenanthrol, 1-hydroxy-2-naphthoic acid and phthalate were detected in the culture solution by GC-MS analysis. In addition, DNA fragments of nahAc gene, encoding α subunit of naphthalene dioxygenase, were amplified by PCR program and sequenced. As a result, it was presumed that the initial cleavage of the aromatic rings on pyrene was occurred at C4 and C5 positions and formed the intermediate 4,5-dihydroxy-4,5-dihydropyrene. This issue had been verified by the interaction analysis between pyrene and the active site of naphthalene dioxygenase in the strain JPN2 by molecular docking. Meanwhile, the differences of the amino acid residues in the active sites of template and target enzymes may be a factor leading to the different biological activity between the strain JPN2 and the other bacteria from the genus Pseudomonas. Additionally, the microcalorimetry analysis displayed that the strain JPN2 had high tolerance for pyrene, and the effect could be negligible under the experimental concentration (100 mg L-1). Consequently, the strain JPN2 was considered as an excellent candidate for the further bioremediation study of pyrene and the other aromatic contaminants.

Biodegradation of Phenanthrene by Pseudomonas sp. JPN2 and Structure-Based Degrading Mechanism Study.

The strain Pseudomonas sp. JPN2 had a high potential to degrade phenanthrene degrading 98.52 % of the initial amount of 100 mg L-1 after 10 days incubation. The analysis of metabolites demonstrated that the cleavage of phenanthrene started at the C9 and C10 positions on the aromatic ring by the dioxygenation reaction, and then further degraded via a phthalate pathway. To understand the interaction between phenanthrene and the amino acid residues in the active site of the target enzyme, a molecular docking simulation was performed. The results showed that the distances of C9-O1 and C10-O2 atoms were 3.47 and 3.67 Å, respectively. The C9 and C10 positions of the phenanthrene ring are much closer to the dioxygen molecule in the active site relative to the other atoms. Therefore, the C9 and C10 positions are vulnerable to attack in the initial oxygenation process.

Microbial Toxicity of a Type of Carbon Dots to Escherichia coli.

Carbon dots (Cdots), as a class of novel photoluminescence nanoprobes, has attracted tremendous interest for its broad application in recent years. Thus, the toxicity and behavior of Cdots in biological systems become important fundamental problems that require significant attention. In this study, Cdots with diameters of 5 nm are produced using mixed-acid treatment. The Cdots exhibit strong yellow fluorescence under UV irradiation and shifted emission peaks as the excitation wavelength is changed. Gram-negative bacteria Escherichia coli (E. coli) are applied as testing model to study the biological effect of Cdots on the cell growth by microcalorimetric, spectroscopic, and microscopic investigation. The introducing of Cdots caused a gradual increase of the maximum heat power (P peak) and the total heat produced (Q total) at low concentrations (0.0-5.00 mg/L). The metabolism rate constant (k) and half inhibitory concentration (IC50) were calculated from the microcalorimetric data. The results indicated that Cdots had a concentration-dependent effect on the growth of E. coli. For confirmation, the growth curves and colony-forming units at different concentration of Cdots were studied. The morphology of E. coli in the absence and presence of Cdots was determined by scanning electron microscopy (SEM). The results of these studies were in agreement well with the analysis explored from microcalorimetry.

An integrated approach of bioassay and molecular docking to study the dihydroxylation mechanism of pyrene by naphthalene dioxygenase in Rhodococcus sp. ustb-1.

Naphthalene dioxygenase (NDO) is the initial enzyme catalyzing the biodegradation of aromatic compounds, and it plays a key role in microbial remediation of polluting sites. In this study, Rhodococcus sp. ustb-1 derived from crude oil was selected to investigate the biodegradation characters and dihydroxylation mechanism of pyrene by an integrated approach of bioassay and molecular docking. The biodegradation experiment proved that the strain ustb-1 shows high effective biodegradability to pyrene with a 70.8% degradation on the 28th day and the metabolite pyrene cis-4,5-dihydrodiol was found. The results of molecular docking indicated that the regions surrounding pyrene are defined by hydrophobic amino acids which are favorable for the binding of dioxygen molecule at C4 and C5 positions of pyrene in a side-on mode. The binding positions of dioxygen are in agreement with the mass spectral analysis of the metabolite pyrene cis-4,5-dihydrodiol. In summary, this study provides a promising explanation for the possible binding behavior between pyrene and active site of NDO.

Concentration-dependent effect of photoluminescent carbon dots on the microbial activity of the soil studied by combination methods.

Carbon dots (Cdots) have a great potential for their widespread biological applications. However, there are a few studies on the biosafety of Cdots. In this work, the biological effect of Cdots on soil microorganism was analyzed by microcalorimetry, soil enzymatic activities, and denaturing gradient gel electrophoresis (DGGE). The addition of Cdots causes a gradual increase of the maximum heat power (P peak) and the growth rate (k) at low concentration of Cdots (0.0-50.00 µg/g). But there is no significant effect of Cdots on the total heat output (Q total). The urease and fluorescein diacetate esterase activities demonstrate that introduction of Cdots to soil has almost no impact on the structure and function of the soil microbial community and microbial processes. The DGGE results exhibit that the control and the Cdots-treated soils display similar patterns, indicating that Cdots have little effect on the microbial community structure.

Rational design and screening study of novel lead compound based on acetohydroxyacid synthase structure.

Acetohydroxyacid synthase (AHAS) is a key target and has extensive application in the process of herbicide discovery. However, the problem of weed resistance is gradually serious with long-term excessive use of commercial AHAS-inhibiting herbicides, and so, it is urgent to develop novel herbicides. In this study, a virtual screening was performed based on the active site of AHAS. Then, the hit-10 compound with the IC50 value of 47.41 mg/L was selected as lead compound based on the biological testing. Subsequently, the optimization design and syntheses of lead compound were carried out according to the analyzing results of mechanism and receptor-/ligand-binding mode. Three novel 5-substituted benzyl-1,3,4-thiadiazol-2-carbamic acid phenyl ester derivatives were designed and synthesized. Bioactive assay results of the three target compounds showed that all of them displayed the higher inhibition than lead compound to AHAS, with the IC50 values in the 23.54-32.05 mg/L range, and the inhibition rates were increased by 30-50%. Finally, we also analyzed the possible inhibitory mechanism of the three target compounds based on the molecular docking between AHAS and target compounds. This study would provide a novel chemical structure for the discovery of novel AHAS herbicides.