A single infusion of engineered long-lived and multifunctional T cells confers durable remission of asthma in mice.

Asthma, the most prevalent respiratory disease, affects more than 300 million people and causes more than 250,000 deaths annually. Type 2-high asthma is characterized by interleukin (IL)-5-driven eosinophilia, along with airway inflammation and remodeling caused by IL-4 and IL-13. Here we utilize IL-5 as the targeting domain and deplete BCOR and ZC3H12A to engineer long-lived chimeric antigen receptor (CAR) T cells that can eradicate eosinophils. We call these cells immortal-like and functional IL-5 CAR T cells (5TIF) cells. 5TIF cells were further modified to secrete an IL-4 mutein that blocks IL-4 and IL-13 signaling, designated as 5TIF4 cells. In asthma models, a single infusion of 5TIF4 cells in fully immunocompetent mice, without any conditioning regimen, led to sustained repression of lung inflammation and alleviation of asthmatic symptoms. These data show that asthma, a common chronic disease, can be pushed into long-term remission with a single dose of long-lived CAR T cells.

Response of microbial communities to exogenous nitrate nitrogen input in black and odorous sediment.

Since nitrate nitrogen (NO3--N) input has proved an effective approach for the treatment of black and odorous river waterbody, it was controversial whether the total nitrogen concentration standard should be raised when the effluent from the sewage treatment plant is discharged into the polluted river. To reveal the effect of exogenous nitrate (NO3--N) on black odorous waterbody, sediments with different features from contaminated rivers were collected, and the changes of physical and chemical characteristics and microbial community structure in sediments before and after the addition of exogenous NO3--N were investigated. The results showed that after the input of NO3--N, reducing substances such as acid volatile sulfide (AVS) in the sediment decreased by 80 % on average, ferrous (Fe2+) decreased by 50 %, yet the changing trend of ammonia nitrogen (NH4+-N) in some sediment samples increased while others decreased. High-throughput sequencing results showed that the abundance of Thiobacillus at most sites increased significantly, becoming the dominant genus in the sediment, and the abundance of functional genes in the metabolome increased, such as soxA, soxX, soxY, soxZ. Network analysis showed that sediment microorganisms evolved from a single sulfur oxidation ecological function to diverse ecological functions, such as nitrogen cycle nirB, nirD, nirK, nosZ, and aerobic decomposition. In summary, inputting an appropriate amount of exogenous NO3--N is beneficial for restoring and maintaining the oxidation states of river sediment ecosystems.

Relationship between 24-h activity behavior and body fat percentage in preschool children: based on compositional data and isotemporal substitution analysis.

OBJECTIVE: This study aims to elucidate the dose‒response relationship between 24-h activity behaviors and body fat percentage (BFP) in Chinese preschool children using a compositional isotemporal substitution model (ISM). METHODS: In a cross-sectional design, 881 children aged 3-6 from urban and rural areas of Jiangxi Province were sampled. Activity behaviors, including sedentary behavior (SB), low-intensity physical activity (LPA), and moderate- to high-intensity physical activity (MVPA), were measured using accelerometers. Sleep patterns were assessed through questionnaires, and BFP was determined by bioelectrical impedance analysis (BIA). The study employed compositional data analysis (CoDA) and ISM to estimate the impact of reallocating durations of different activity behaviors on BFP. RESULTS: Higher BFP was found in urban vs. rural children, decreasing with age. Overweight and obesity rates were 10.6% and 7.6%, respectively, above national averages. MVPA and LPA were negatively correlated with BFP, while SB was positively correlated. A 30-min MVPA reduction significantly increased zBFR, particularly in overweight children. Gender-specific nuances revealed that boys' MVPA negatively influenced zBFP (ß = -0.155), P < 0.05), while girls' SB positively impacted zBFP (ß = 0.636, P < 0.01). Isotemporal simulations emphasized amplified effects in overweight children, with boys' zBFR rising rapidly when MVPA was substituted and girls displaying a notable substitution effect between SB and LPA. CONCLUSION: BFP is closely linked to 24-h activity behaviors, notably in overweight and obese preschoolers. ISM identified MVPA as a critical influencer, with a 30-min reduction substantially increasing BFP. Gender disparities were evident, implicating MVPA in boys and LPA and SB in girls.

Horizontal transmission of a rice bacterial pathogen Pantoea ananatis among plants by rice planthoppers.

Pantoea ananatis is a bacterium commonly found in various agronomic crops and agricultural pests. In this study, we present findings on a genome-reduced strain of P. ananatis, known as Lstr, which was initially isolated from Laodelphax striatellus (small brown rice planthopper, SBPH). We identified Lstr as a plant pathogen causing disease in rice using Koch's postulates. The pathogenicity of Lstr on rice is comparable to that of Xanthomonas oryzae pv. oryzae, the main causative agent of rice bacterial blight. Through a series of experiments involving live insects, molecular investigations, and microscopy, we find that Lstr can accumulate within SBPH. Subsequently, Lstr can be transmitted from SBPH to rice plants, resulting in leaf blight, and can also be transmitted to other SBPH individuals. Collectively, our results suggest that SBPH serves as a vector for P. ananatis Lstr in rice plants. P. ananatis may encounter susceptible insect populations and become endemic through horizontal transmission from these insects. This could also be valuable for predicting future occurrences of bacterial leaf blight in rice and other crops caused by P. ananatis.

Controllable Phase Transition Properties in VO2 Films via Metal-Ion Intercalation.

VO2 has shown great promise for sensors, smart windows, and energy storage devices, because of its drastic semiconductor-to-metal transition (SMT) near 340 K coupled with a structural transition. To push its application toward room-temperature, effective transition temperature (Tc) tuning in VO2 is desired. In this study, tailorable SMT characteristics in VO2 films have been achieved by the electrochemical intercalation of foreign ions (e.g., Li ions). By controlling the relative potential with respect to Li/Li+ during the intercalation process, Tc of VO2 can be effectively and systematically tuned in the window from 326.7 to 340.8 K. The effective Tc tuning could be attributed to the observed strain and lattice distortion and the change of the charge carrier density in VO2 introduced by the intercalation process. This demonstration opens up a new approach in tuning the VO2 phase transition toward room-temperature device applications and enables future real-time phase change property tuning.

KOBAS-i: intelligent prioritization and exploratory visualization of biological functions for gene enrichment analysis.

Gene set enrichment (GSE) analysis plays an essential role in extracting biological insight from genome-scale experiments. ORA (overrepresentation analysis), FCS (functional class scoring), and PT (pathway topology) approaches are three generations of GSE methods along the timeline of development. Previous versions of KOBAS provided services based on just the ORA method. Here we presented version 3.0 of KOBAS, which is named KOBAS-i (short for KOBAS intelligent version). It introduced a novel machine learning-based method we published earlier, CGPS, which incorporates seven FCS tools and two PT tools into a single ensemble score and intelligently prioritizes the relevant biological pathways. In addition, KOBAS has expanded the downstream exploratory visualization for selecting and understanding the enriched results. The tool constructs a novel view of cirFunMap, which presents different enriched terms and their correlations in a landscape. Finally, based on the previous version's framework, KOBAS increased the number of supported species from 1327 to 5944. For an easier local run, it also provides a prebuilt Docker image that requires no installation, as a supplementary to the source code version. KOBAS can be freely accessed at http://kobas.cbi.pku.edu.cn, and a mirror site is available at http://bioinfo.org/kobas.

Transcriptome analysis of Fenneropenaeus merguiensis in response to Vibrio proteolyticus infection.

In recent years, due to the destruction of the culture environment and serious ecological pressure, especially in the process of culture, residual bait, faeces and fishery drug abuse will lead to the accumulation of harmful metabolites such as ammonia nitrogen and nitrite, and biological denitrification is the most economical and effective method to remove the single. Therefore, in this study, a nitrite removal strain XA19 was isolated and screened from a shrimp biofloc culture pond. This strain was identified as a clade of Vibrio proteolyticus because the homology between XA19 and V. proteolyticus WDVP was as high as 99.86% by using 16S rDNA gene sequence analysis and NCBI database comparison. Scanning electron microscopy images showed that V. proteolyticus is short-rod-shaped with a curved body and no budding spores, pods and flagella. Antimicrobial susceptibility test proved that V. proteolyticus was resistant to ampicillin, oxacillin, penicillin, vancomycin and clindamycin. In the median lethal concentration 50 (LC50 ) test, at 7-day post-infection (dpi), LC50 of V. proteolyticus for Fenneropenaeus merguiensis was 1.69 × 104 CFU/mL. Transcriptome sequencing analysis was carried out on hepatopancreas of F. merguiensis at 24 and 48 hpi. A total of 176 differentially expressed genes (DEGs) were screened at 24 hpi, including 104 up-regulated DEGs and 72 down-regulated DEGs, and a total of 52 DEGs were screened at 48 hpi, including 32 up-regulated DEGs and 20 down-regulated DEGs. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs, many immune-related signalling pathways were significantly enriched, including Hippo signalling pathway, phagosome, Toll and Imd signalling pathways and Wnt signalling pathway. In addition, some pathways related to Warburg effect were also enriched, including Glycolysis/Gluconeogenesis, Biosynthesis of amino acids, amino sugar and nucleotide sugar metabolism and so on. In this study, the toxicity and drug sensitivity of V. proteolyticus were systematically studied, and the immune response of hepatopancreas of F. merguiensis to V. proteolyticus infection was preliminarily revealed from the molecular level. The results may provide a reference for the prevention and control of V. proteolyticus.

Angelica sinensis polysaccharide ameliorates nonalcoholic fatty liver disease via restoring estrogen-related receptor α expression in liver.

Angelica sinensis polysaccharide (ASP) showed increasingly recognized hepatoprotective effects and lipid regulation. Because polysaccharides are typically degraded into fragments or short-chain fatty acids in the gut, rather than being absorbed in their intact form, it is worth pondering why ASP can regulate hepatic lipid metabolism and protect the liver from damage caused by lipid accumulation. In vivo and in vitro nonalcoholic fatty liver disease (NAFLD) models with lipid accumulation were established to investigate the effect and potential mechanisms of ASP on hepatic fat accumulation. Our results showed that ASP remodeled the composition and abundance of the gut microbiota in high-fat diet-fed mice and increased their levels of propionate (0.92 ± 0.30 × 107 vs. 2.13 ± 0.52 × 107 ) and butyrate (1.83 ± 1.31 × 107 vs. 6.39 ± 1.44 × 107 ). Sodium propionate significantly increased the expression of estrogen-related receptor α (ERRα) in liver cells (400 mM sodium propionate for 2.19-fold increase) and alleviated the progress of NAFLD in methionine-choline-deficient diet model. Taken together, our study demonstrated that ASP can regulate hepatic lipid metabolism via propionate/ERRα pathway and ultimately relieving NAFLD. Our findings demonstrate that ASP can be used as a health care product or food supplement to prevent NAFLD.

Tunable Tribovoltaic Effect via Metal-Insulator Transition.

Tribovoltaic direct-current (DC) nanogenerator made of dynamic semiconductor heterojunction is emerging as a promising mechanical energy harvesting technology. However, fundamental understanding of the mechano-electronic carrier excitation and transport at dynamic semiconductor interfaces remains to be investigated. Here, we demonstrated for the first time, that tribovoltaic DC effect can be tuned with metal-insulator transition (MIT). In a representative MIT material (vanadium dioxide, VO2), we found that the short-circuit current (ISC) can be enhanced by >20 times when the material is transformed from insulating to metallic state upon static or dynamic heating, while the open-circuit voltage (VOC) turns out to be unaffected. Such phenomenon may be understood by the Hubbard model for Mott insulator: orders' magnitude increase in conductivity is induced when the nearest hopping changes dramatically and overcomes the Coulomb repulsion, while the Coulomb repulsion giving rise to the quasi-particle excitation energy remains relatively stable.

Abnormal subchondral trabecular bone remodeling in knee osteoarthritis under the influence of knee alignment.

OBJECTIVE: This study aimed to investigate the abnormal subchondral trabecular bone (STB) remodeling in knee osteoarthritis (OA) under the influence of knee alignment [hip-knee-ankle (HKA) angle]. DESIGN: Forty-one patients with knee OA underwent radiographic examination before total knee arthroplasty (TKA) for the measurement of HKA angle. Tibial plateau specimens obtained during TKA were used for histomorphometric analyses to assess STB remodeling and cartilage degradation. Tartrate-resistant acidic phosphatase (TRAP) staining was used to test osteoclast activity. Osterix, osteocalcin, and sclerostin expression in the STB were determined using immunohistochemistry. RESULTS: The interaction between HKA angle and side (medial vs lateral of tibial plateau) was the main significant influence factor for STB remodeling and microstructure. The STB with the deviation of the knee alignment was accompanied by obvious abnormal bone remodeling and microstructural sclerosis. Bone volume fraction (BV/TV) was the only significant influence factor for OARSI score, the larger the BV/TV of STB, the higher the OARSI score of cartilage. Moreover, the tibial plateau affected by alignment had more TRAP + osteoclasts, Osterix + osteoprogenitors, and osteocalcin + osteoblasts and fewer sclerostin + osteocytes. CONCLUSIONS: The variation of tibial plateau STB remodeling activity and microstructure was associated with HKA angle and cartilage degradation. Knee malalignment may cause abnormal STB remodeling and microstructural sclerosis, which may potentially affect load stress transmission from the cartilage to the STB, thus resulting in accelerated knee OA progression.

Multifunctional Metal-Oxide Nanocomposite Thin Film with Plasmonic Au Nanopillars Embedded in Magnetic La0.67Sr0.33MnO3 Matrix.

Searching for multifunctional materials with tunable magnetic and optical properties has been a critical task toward the implementation of future integrated optical devices. Vertically aligned nanocomposite (VAN) thin films provide a unique platform for multifunctional material designs. Here, a new metal-oxide VAN has been designed with plasmonic Au nanopillars embedded in a ferromagnetic La0.67Sr0.33MnO3 (LSMO) matrix. Such Au-LSMO nanocomposite presents intriguing plasmon resonance in the visible range and magnetic anisotropy property, which are functionalized by the Au and LSMO phase, respectively. Furthermore, the vertically aligned nanostructure of metal and dielectric oxide results in the hyperbolic property for near-field electromagnetic wave manipulation. Such optical and magnetic response could be further tailored by tuning the composition of Au and LSMO phases.

Hyaluronic acid-coated and Olaparib-loaded PEI - PLGA nanoparticles for the targeted therapy of triple negative breast cancer.

AIM: To prepare the hyaluronic acid-coated Olaparib-loaded PEI - PLGA nanoparticles (HA-Ola-PPNPs) and investigate their tumour-targeted anticancer effect. METHODS: The synthesis of HA-Ola-PPNPs was verified by DLS, TEM and SEM, followed was measured its cytotoxicity using CCK-8 assay. Confocal microscopy was used to observe the cellular uptake. Cell apoptosis was analysed by flow cytometry, biological SEM, and TEM. The expression of related proteins within the tumour site was investigated by immunostaining. RESULTS: The prepared HA-Ola-PPNPs showed a diameter of ∼160 nm with a negatively charged surface (-16.9 ± 2.7 mV) and sustained drug release behaviour. And the encapsulation efficiency of HA-Ola-PPNPs was 78.63 ± 5.29%. HA-Ola-PPNPs exhibited efficient in vitro and in vivo antitumor activities. HA-Ola-PPNPs induced cell apoptosis by upregulating Bax, Cytochrome C, and Caspase 3, downregulating Bcl-2 in breast cancer-bearing mice. CONCLUSIONS: According to the results, the Ola-loaded and HA-coated PEI - PLGA nanoparticles could be considered as a powerful tumour-targeted drug delivery system for TNBC treatment.

ZnO-AuxCu1-x Alloy and ZnO-AuxAl1-x Alloy Vertically Aligned Nanocomposites for Low-Loss Plasmonic Metamaterials.

Hyperbolic metamaterials are a class of materials exhibiting anisotropic dielectric function owing to the morphology of the nanostructures. In these structures, one direction behaves as a metal, and the orthogonal direction behaves as a dielectric material. Applications include subdiffraction imaging and hyperlenses. However, key limiting factors include energy losses of noble metals and challenging fabrication methods. In this work, self-assembled plasmonic metamaterials consisting of anisotropic nanoalloy pillars embedded into the ZnO matrix are developed using a seed-layer approach. Alloys of AuxAl1-x or AuxCu1-x are explored due to their lower losses and higher stability. Optical and microstructural properties were explored. The ZnO-AuxCu1-x system demonstrated excellent epitaxial quality and optical properties compared with the ZnO-AuxAl1-x system. Both nanocomposite systems demonstrate plasmonic resonance, hyperbolic dispersion, low losses, and epsilon-near-zero permittivity, making them promising candidates towards direct photonic integration.

Superhydrophobic Films with Enhanced Corrosion Resistance and Self-Cleaning Performance on an Al Alloy.

In this article, a novel and facile method is used to construct superhydrophobic surfaces on aluminum alloys. A solution of aluminum chloride hexahydrate and N-dodecyltrimethoxysilane (DTMS) in ethanol was used as the electrolyte solution. The hydrolysis of DTMS was accelerated during the electrodeposition process, and the hydrolysate was bonded to a pretreated aluminum surface. The prepared aluminum alloy sample exhibits both superhydrophobicity (the surface water contact angle reached 155°) and excellent corrosion resistance. The inhibition efficiency of this sample is as high as 99.9% in 3.5 wt % NaCl solution, which remains at 98% even after 30 days of immersion. Thus, our fabrication can be well applied to the field of marine corrosion protection. Therefore, the working mechanism was discussed by confocal Raman microspectroscopy (CRM). In addition, the investigation by CRM and electrochemical impedance spectroscopy (EIS) also indicates that superhydrophobic samples show good stability in NaCl solution. The fabrication method can inspire new ideas for the construction of superhydrophobic aluminum alloys in the marine environment.

Vertically Aligned AgxAu1-x Alloyed Nanopillars Embedded in ZnO as Nanoengineered Low-Loss Hybrid Plasmonic Metamaterials.

Hybrid plasmonic metamaterials offer a pathway to exotic properties and technologically important applications including subdiffraction imaging and plasmonic energy harvesting. Challenges remain for practical applications including high absorption losses of noble metals and tedious growth/fabrication processes. In this work, a self-assembled hybrid plasmonic metamaterial consisting of anisotropic AgxAu1-x alloy nanopillars embedded in a ZnO matrix has been successfully grown. The chemical composition of the nanoalloy was determined to be Ag61Au39. The microstructure and optical properties arising from ZnO-Ag61Au39 alloyed hybrid systems were investigated and compared with that of the ZnO-Ag particle-in-matrix nanocomposite and the ZnO-Au vertically aligned nanocomposite. The ZnO-Ag61Au39 hybrid system demonstrates anisotropic morphology, excellent epitaxial quality, and enhanced optical properties, including surface plasmon resonance, hyperbolic dispersion, low absorption losses, and numerous epsilon-near-zero permittivity points, making it a promising candidate for practical applications of hybrid plasmonic metamaterials.

Energy output modalities of shockwave lithotripsy in the treatment of urinary stones: escalating or fixed voltage? A systematic review and meta-analysis.

PURPOSE: To compare the effectiveness and safety of escalating and fixed energy output modalities of shockwave lithotripsy (SWL) in the treatment of urinary stones. METHODS: A systematic literature search using PubMed, Embase, Cochrane Library and Web of Science was performed to obtain relevant studies up to December 2018. Summarized mean differences (MDs) and risk differences (RDs) with 95% confidence intervals (CIs) were used for comparing continuous and dichotomous variables, respectively. RESULTS: Six RCTs including 775 patients were identified. In the overall pooled outcomes, no significant difference was detected between escalating and fixed voltage group regarding initial and final success rate (SR) and stone-free status (SFS), auxiliary procedure and complication (hematoma, febrile episode, and pain) rate. However, when shockwave frequency ≥ 90 shocks/min, total shocks per session ≤ 3000, or 1-3 SWL sessions were performed, escalating group was associated with significantly higher SR1 (defined as SFS + fragments ≤ 4 mm); in addition, escalating group brought significantly less hematoma when total shocks per session ≤ 3000. CONCLUSIONS: Escalating voltage SWL offered comparable safety and effectiveness to that of fixed voltage SWL. However, escalating voltage SWL could be recommended in following conditions: (1) shockwave frequency ≥ 90 shocks/min, total shocks per session ≤ 3000, or 1-3 SWL sessions, for better stone removal; (2) total shocks per session ≤ 3000, for less hematoma formation.

Research into the hemocyte immune response of Fenneropenaeus merguiensis under decapod iridescent virus 1 (DIV1) challenge using transcriptome analysis.

The banana shrimp (Fenneropenaeus merguiensis) is a common cultural species worldwide. With the development of the shrimp farming industry, increasing number of diseases have emerged and cause huge impacts. Decapod iridescent virus 1 (DIV1) is a new virus of the family Iridoviridae isolated in China that causes very high mortality in shrimp. In this study, DIV1 and PBS were injected into two groups of shrimp, and hemocytes were collected for comparative transcriptomic analysis. We confirmed that F. merguiensis was the new host of DIV1 by nested PCR. A total of 100,759 unigenes were assembled from the control group and the DIV1 infected group, with an average length of 733.06 bp and N50 of 1136 bp. Significant hits were found in 21,465 unigenes compared to known sequences in major databases including COG (33.30%), GO (42.17%), KEGG (46.76%), KOG (61.37%), Pfam (66.90%), Swissprot (54.21%) and Nr (93.86%). A total of 1003 differentially expressed genes (DEGs) were identified, including 929 up-regulated genes and 74 down-regulated genes. Several known immune-related genes, including caspase, C-type lectin, Wnt5 and integrin, were among the differentially expressed transcripts. A total of 14,459 simple sequence repeats, including 8128 monomers, 3276 dimers, 1693 trimers, 150 quadmers, 4 pentamers and 16 hexamers, were found in the transcriptomic dataset. Our study is the first comprehensive investigation of the transcriptomic response to DIV1 infection in F. merguiensis. Collectively, these results not only provide valuable information for characterizing the immune mechanisms of the shrimp responses to DIV1 infection, they open new ways for the study of the molecular mechanisms of DIV1 infection in F. merguiensis.

Dietary supplementation with polypeptides improved growth performance, antibacterial immune and intestinal microbiota structure of Litopenaeus vannamei.

Antibacterial peptides (AMPs) are expected to replace some or all of the antibiotics and become a new feed additive. However, the high production cost and unclear mechanism limited the application of AMPs. In this research, the effects of a commercial polypeptide (Polypeptide S100) whose main components are AMPs on the growth, antibacterial immune and intestinal microbial of Litopenaeus vannamei were study. L. vannamei (initial weight of 0.16 ±â€¯0.03 g) were fed for 123 days with basal diet added Polypeptide S100 at two levels each (0.5% and 1%) as experimental groups, and a basal diet as control. Dietary inclusion of Polypeptide S100 at 1% level significantly increased the weight gain (WG) and specific growth rate (SGR) of L. vannamei. The survival rates of L. vannamei in 0.5% and 1% Polypeptide S100 groups were significantly higher than the control when infected by Vibrio harveyi but not Vibrio parahaemolyticus. The activities of total superoxide dismutase (T-SOD) and lysozyme (LZM) in the two experimental groups were all significantly higher than the control. Differently, the activities of amylase (AMS) and lipase (LPS) were significantly higher in 0.5% Polypeptide S100 group but lower in 1.0% Polypeptide S100 group. Illumina MiSeq high-throughput sequencing showed that the dominant phyla in the intestine of L. vannamei were Proteobacteria, followed by Actinobacteria, Bacteroidetes, Chloroflexi, Cyanobacteria, Fusobacteria and Tenericutes, and the abundance of predominant phyla Cyanobacteria were upregulated significantly in the experimental groups. At the family level, significant increase was observed in Pseudomonadaceae and Xanthomonadaceae but decrease in Vibrionaceae in the 1.0% Polypeptide S100 group. The abundance of predominant genus Photobacterium were obviously downregulated in the two experimental groups. Unlikely, the abundance of Pseudomonas and Stenotrophomonas were distinctly increased in the 1.0% Polypeptide S100 group but not significantly different from the control in 0.5% Polypeptide S100 group. All these results suggested that Polypeptide S100 could improve the growth performance, antibacterial immune and intestinal microbiota structure of L. vannamei.

Investigating the Binding Mode of Reversible LSD1 Inhibitors Derived from Stilbene Derivatives by 3D-QSAR, Molecular Docking, and Molecular Dynamics Simulation.

Overexpression of lysine specific demethylase 1 (LSD1) has been found in many cancers. New anticancer drugs targeting LSD1 have been designed. The research on irreversible LSD1 inhibitors has entered the clinical stage, while the research on reversible LSD1 inhibitors has progressed slowly so far. In this study, 41 stilbene derivatives were studied as reversible inhibitors by three-dimensional quantitative structure-activity relationship (3D-QSAR). Comparative molecular field analysis (CoMFA q 2 = 0.623, r 2 = 0.987, r pred 2 = 0.857) and comparative molecular similarity indices analysis (CoMSIA q 2 = 0.728, r 2 = 0.960, r pred 2 = 0.899) were used to establish the model, and the structure-activity relationship of the compounds was explained by the contour maps. The binding site was predicted by two different kinds of software, and the binding modes of the compounds were further explored. A series of key amino acids Val288, Ser289, Gly314, Thr624, Lys661 were found to play a key role in the activity of the compounds. Molecular dynamics (MD) simulations were carried out for compounds 04, 17, 21, and 35, which had different activities. The reasons for the activity differences were explained by the interaction between compounds and LSD1. The binding free energy was calculated by molecular mechanics generalized Born surface area (MM/GBSA). We hope that this research will provide valuable information for the design of new reversible LSD1 inhibitors in the future.

Index for nitrate dosage calculation on sediment odor control using nitrate-dependent ferrous and sulfide oxidation interactions.

Nitrate-driven sulfide and ferrous oxidation have received great concern in researches on sediments odor control with calcium nitrate addition. However, interrelations among sulfide oxidation, ferrous oxidation and their associated microbes during the nitrate reduction process are rarely reported. In this work, a nNO3/n(S+Fe) ratio (mole ratio of NO3- concentration to S2- and Fe2+ concentration) was first introduced as an index for calcium nitrate dosage calculation. Then certain amount of calcium nitrate was added to four sediment systems with various sulfide and ferrous initial concentration to create four gradients of nNO3/n(S+Fe) ratio (0.6, 0.9, 1.5 and 2.0) for treatment. Furthermore, the significant variations of sulfide and ferrous oxidation, microbial diversity and community structure were observed. The results revealed that at low nNO3/n(S+Fe) ratio (0.6 and 0.9) systems, sulfide seemed prior to ferrous to be oxidized and no obvious ferrous oxidation occurred. Meanwhile, sulfide oxidizing associated genus Sulfurimonas sp. became dominant in these systems. In contrast, sulfide and ferrous oxidation rate increased when nNO3/n(S+Fe) ratio reached 1.5 and 2.0 (two and three times of theoretically required amount for sulfide and ferrous oxidation), which made Thiobacillus sp. more dominant than Sulfurimonas sp. Hence, when nNO3/n(S+Fe) ratio of 1.5 and 2.0 were used, sulfide and ferrous could be simultaneously oxidized and no sulfide regeneration appeared in two months. These results demonstrated that for sulfide- and ferrous-rich sediment treatment, the nitrate consumed by ferrous oxidation should be taken into account when calculating the nitrate injecting dosage. Moreover, nNO3/n(S+Fe) ratio was feasible as a key parameter to control the oxidation process and as an index for calcium nitrate dosage calculation.