Reference genome and annotation updates lead to contradictory prognostic predictions in gene expression signatures: a case study of resected stage I lung adenocarcinoma.

RNA-sequencing enables accurate and low-cost transcriptome-wide detection. However, expression estimates vary as reference genomes and gene annotations are updated, confounding existing expression-based prognostic signatures. Herein, prognostic 9-gene pair signature (GPS) was applied to 197 patients with stage I lung adenocarcinoma derived from previous and latest data from The Cancer Genome Atlas (TCGA) processed with different reference genomes and annotations. For 9-GPS, 6.6% of patients exhibited discordant risk classifications between the two TCGA versions. Similar results were observed for other prognostic signatures, including IRGPI, 15-gene and ORACLE. We found that conflicting annotations for gene length and overlap were the major cause of their discordant risk classification. Therefore, we constructed a prognostic 40-GPS based on stable genes across GENCODE v20-v30 and validated it using public data of 471 stage I samples (log-rank P < 0.0010). Risk classification was still stable in RNA-sequencing data processed with the newest GENCODE v32 versus GENCODE v20-v30. Specifically, 40-GPS could predict survival for 30 stage I samples with formalin-fixed paraffin-embedded tissues (log-rank P = 0.0177). In conclusion, this method overcomes the vulnerability of existing prognostic signatures due to reference genome and annotation updates. 40-GPS may offer individualized clinical applications due to its prognostic accuracy and classification stability.

A Highly Sensitive Model Based on Graph Neural Networks for Enzyme Key Catalytic Residue Prediction.

Determining the catalytic site of enzymes is a great help for understanding the relationship between protein sequence, structure, and function, which provides the basis and targets for designing, modifying, and enhancing enzyme activity. The unique local spatial configuration bound to the substrate at the active center of the enzyme determines the catalytic ability of enzymes and plays an important role in the catalytic site prediction. As a suitable tool, the graph neural network can better understand and identify the residue sites with unique local spatial configurations due to its remarkable ability to characterize the three-dimensional structural features of proteins. Consequently, a novel model for predicting enzyme catalytic sites has been developed, which incorporates a uniquely designed adaptive edge-gated graph attention neural network (AEGAN). This model is capable of effectively handling sequential and structural characteristics of proteins at various levels, and the extracted features enable an accurate description of the local spatial configuration of the enzyme active site by sampling the local space around candidate residues and special design of amino acid physical and chemical properties. To evaluate its performance, the model was compared with existing catalytic site prediction models using different benchmark datasets and achieved the best results on each benchmark dataset. The model exhibited a sensitivity of 0.9659, accuracy of 0.9226, and area under the precision-recall curve (AUPRC) of 0.9241 on the independent test set constructed for evaluation. Furthermore, the F1-score of this model is nearly four times higher than that of the best-performing similar model in previous studies. This research can serve as a valuable tool to help researchers understand protein sequence-structure-function relationships while facilitating the characterization of novel enzymes of unknown function.

Simultaneous acetone-butanol-ethanol fermentation, gas stripping, and full-cell-catalyzed esterification for effective production of butyl oleate.

In this study, aiming to improve the economic feasibility of acetone-butanol-ethanol (ABE) fermentation process, generate valuable products and extend the product chain, esterification catalyzed by Candida sp. 99-125 cells was hybrid with the ABE fermentation-gas-stripping integration system. The gas-stripping condensate that contained concentrated ABE products was directly used for esterification without the participation of toxic organic solvents. Full-cell catalysis temperature and the cell dosage rate on oleate production were evaluated and optimized in the esterification process. Under the optimized conditions (35 °C, 8% of cells), ~ 68% of butyl oleate and ~ 12% of ethyl oleate were obtained after 4 h of esterification. The Candida sp. 99-125 cells were able to be reused for at least four cycles. The novel cascade process showed environmental benefits, which also showed promising in improving the economic feasibility of the conventional ABE fermentation process.

Austin-Type Meroterpenoids from Fungi Reported in the Last Five Decades: A Review.

Austin was first isolated as a novel polyisoprenoid mycotoxin from Aspergillus ustus in 1976. Subsequently, some new austin-type meroterpenoids (ATMTs) have been continually found. This review attempts to give a comprehensive summary of progress on the isolation, chemical structural features, biological activities, and fungal biodiversity of 104 novel ATMTs from 5 genera of terrestrial- and marine-derived fungi reported from October 1976 to January 2023. The genera of Penicillium and Aspergillus are the two dominant producers, producing 63.5% and 30.8% of ATMTs, respectively. Moreover, about 26.9% of ATMTs display various pronounced bioactivities, including insecticidal, anti-inflammatory, cytotoxicity, antibacterial, and PTP1B inhibitory activities. The chemical diversity and potential activities of these novel fungal ATMTs are reviewed for a better understanding, and a relevant summary focusing on the source fungi and their taxonomy is provided to shed light on the future development and research of austin-type meroterpenoids.

Impact of nitrogen application and crop stage on epiphytic microbial communities on silage maize leaf surfaces.

This study aimed to examine the impact of nitrogen (N) fertilization on phyllosphere microorganisms in silage maize (Zea mays) to enhance the production of high-quality silage. The effects of different N application rates (160, 240, and 320 kg ha-1) and maturity stages (flowering and dough stages) on microbial diversity, abundance and physiochemical properties of the leaf surfaces were evaluated in a field experiment. The results showed that N application rates did not significantly impact the abundance of lactic acid bacteria (LAB), aerobic bacteria (AB), yeasts, or molds on the leaf surfaces. However, these microbes were more abundant during the flowering stage compared to the dough stage. Furthermore, the N application rate had no significant impact on inorganic phosphorus, soluble sugar, free amino acids, total phenolic content, and soluble protein concentrations, or pH levels on the leaf surfaces. Notably, these chemical indices were lower during the dough stage. The abundance of Pantoea decreased with higher N application rates, while that of other microorganisms did not changes significantly. The abundance of AB, LAB, yeasts, and molds were positively correlated with soluble sugar, soluble protein, inorganic phosphorus, free amino acids, and total phenolic concentrations on leaf surfaces. Moreover, water loss was negatively correlated with the abundance of AB, LAB, yeasts, and molds, whereas water retention capacity and stomatal density were positively correlated with microbial abundance. We recommend applying an optimal N rate of 160 kg ha-1 to silage maize and harvesting at the flowering stage is recommended.

Prediction of Plasticizer Property Based on an Improved Genetic Algorithm.

Different plasticizers have obvious differences in plasticizing properties. As one of the important indicators for evaluating plasticization performance, the substitution factor (SF) has great significance for product cost accounting. In this research, a genetic algorithm with "variable mutation probability" was developed to screen the key molecular descriptors of plasticizers that are highly correlated with the SF, and a SF prediction model was established based on these filtered molecular descriptors. The results show that the improved genetic algorithm greatly improved the prediction accuracy in different regression models. The coefficient of determination (R2) for the test set and the cross-validation both reached 0.92, which is at least 0.15 higher than the R2 of the unimproved genetic algorithm. From the results of the selected descriptors, most of the descriptors focused on describing the branching of the molecule, which is consistent with the view that the branching chain plays an important role in the plasticization process. As the first study to establish the relationship between plasticizer SF and plasticizer molecular structure, this work provides a basis for subsequent plasticizer performance and evaluation system modeling.

Polymer/silica hybrid hollow nanospheres with pH-sensitive drug release in physiological and intracellular environments.

Hybrid hollow nanospheres of chitosan-silica templated by chitosan-poly(acrylic acid) nanoparticles are fabricated in a complete aqueous system, which provide a pH-sensitive switch in physiological and sub-cell environments for the release of loaded drug.

Novel distillation process for effective and stable separation of high-concentration acetone-butanol-ethanol mixture from fermentation-pervaporation integration process.

BACKGROUND: One of the major obstacles of acetone-butanol-ethanol (ABE) fermentation from renewable biomass resources is the energy-intensive separation process. To decrease the energy demand of the ABE downstream separation processes, hybrid in situ separation system with conventional distillation is recognized as an effective method. However, in the distillation processes, the high reflux ratio of the ethanol column and the accumulation of ethanol on top of the water and butanol columns led to poor controllability and high operation cost of the distillations. In this study, vacuum distillation process which is based on a decanter-assisted ethanol-butanol-water recycle loop named E-TCD sequence was developed to improve the conventional separation sequence for ABE separation. The permeate of in situ pervaporation system was used as the feed. RESULTS: The distillation processes were simulated and optimized by iterative strategies. ABE mixture with acetone, butanol and ethanol concentrations of 115.8 g/L, 191.4 g/L and 17.8 g/L (the other composition was water) that obtained from fermentation-pervaporation integration process was used as the feed. A plant scaled to 1025 kg/h of ABE mixture was performed, and the product purities were 100 wt% of butanol, 99.7 wt% of acetone and 95 wt% of ethanol, respectively. Results showed that only 5.3 MJ/kg (of butanol) was required for ABE separation, which was only 37.54% of the energy cost in conventional distillation processes. CONCLUSIONS: Compared with the drawbacks of ethanol accumulation in butanol-water recycle loop and the extremely high recovery rate of ethanol in conventional distillation processes, simulation results obtained in the current work avoided the accumulation of ethanol based on the novel E-TCD sequence.

Bio-plasticizer production by hybrid acetone-butanol-ethanol fermentation with full cell catalysis of Candida sp. 99-125.

Hybrid process that integrated fermentation, pervaporation and esterification was established aiming to improve the economic feasibility of the conventional acetone-butanol-ethanol (ABE) fermentation process. Candida sp 99-125 cells were used as full-cell catalyst. The feasibility of batch and fed-batch esterification using the ABE permeate of pervaporation (ranging from 286.9 g/L to 402.9 g/L) as substrate were compared. Valuable butyl oleate was produced along with ethyl oleate. For the batch esterification, due to severe inhibition of substrate to lipase, the yield of butyl oleate and ethyl oleate were only 24.9% and 3.3%, respectively. In contrast, 75% and 11.8% of butyl oleate and ethyl oleate were obtained, respectively, at the end of the fed-batch esterification. The novel integration process provides a promising strategy for in situ upgrading ABE products.

Feasibility of polyethylene composites reinforced by distillers dried fibers with solubles (DDFS) after different generations of ethanol fermentation.

In order to effectively evaluate the distillers dried fibers with solubles (DDFS) obtained from biorefinery processes, sorghum distiller (SD), cassava distiller (CD) and corn cob distiller (CCD) residuals from different generation bioethanol plants were used as the reinforcing phase for polyethylene composites. The mechanical performances and the physical properties of the polyethylene/DDFS composites were evaluated. The results showed that the CCD reinforced specimen offered the best mechanical performances, with a flexural strength of 21.8 ± 2.2 MPa and a tensile strength of 39.7 ± 3.2 MPa. After multigelation, the retention ratios of the rupture modulus and the elasticity modulus of the CCD reinforced specimen reached 88.7 ± 6.7% and 84.1 ± 2.7%, while after 2000 h of xenon lamp weathering they reached 96.2 ± 4.7% and 82 ± 1.8%, respectively. Hybridizing the biorefinery process with the process of composites production was feasible.

Two-stage pervaporation process for effective in situ removal acetone-butanol-ethanol from fermentation broth.

Two-stage pervaporation for ABE recovery from fermentation broth was studied to reduce the energy cost. The permeate after the first stage in situ pervaporation system was further used as the feedstock in the second stage of pervaporation unit using the same PDMS/PVDF membrane. A total 782.5g/L of ABE (304.56g/L of acetone, 451.98g/L of butanol and 25.97g/L of ethanol) was achieved in the second stage permeate, while the overall acetone, butanol and ethanol separation factors were: 70.7-89.73, 70.48-84.74 and 9.05-13.58, respectively. Furthermore, the theoretical evaporation energy requirement for ABE separation in the consolidate fermentation, which containing two-stage pervaporation and the following distillation process, was estimated less than ∼13.2MJ/kg-butanol. The required evaporation energy was only 36.7% of the energy content of butanol. The novel two-stage pervaporation process was effective in increasing ABE production and reducing energy consumption of the solvents separation system.

The optimization of l-lactic acid production from sweet sorghum juice by mixed fermentation of Bacillus coagulans and Lactobacillus rhamnosus under unsterile conditions.

The cost reduction of raw material and sterilization could increase the economic feasibility of l-lactic acid fermentation, and the development of an cost-effective and efficient process is highly desired. To improve the efficiency of open fermentation by Lactobacillus rhamnosus based on sweet sorghum juice (SSJ) and to overcome sucrose utilization deficiency of Bacillus coagulans, a mixed fermentation was developed. Besides, the optimization of pH, sugar concentration and fermentation medium were also studied. Under the condition of mixed fermentation and controlled pH, a higher yield of 96.3% was achieved, compared to that (68.8%) in sole Lactobacillus rhamnosus fermentation. With an optimized sugar concentration and a stepwise-controlled pH, the l-lactic acid titer, yield and productivity reached 121gL(-1), 94.6% and 2.18gL(-1)h(-1), respectively. Furthermore, corn steep powder (CSP) as a cheap source of nitrogen and salts was proved to be an efficient supplement to SSJ in this process.

Co-generation of microbial lipid and bio-butanol from corn cob bagasse in an environmentally friendly biorefinery process.

Biorefinery process of corn cob bagasse was investigated by integrating microbial lipid and ABE fermentation. The effects of NaOH concentration on the fermentations performance were evaluated. The black liquor after pretreatment was used as substrate for microbial lipid fermentation, while the enzymatic hydrolysates of the bagasse were used for ABE fermentation. The results demonstrated that under the optimized condition, the cellulose and hemicellulose in raw material could be effectively utilized. Approximate 87.7% of the polysaccharides were converted into valuable biobased products (∼175.7g/kg of ABE along with ∼36.6g/kg of lipid). At the same time, almost half of the initial COD (∼48.9%) in the black liquor could be degraded. The environmentally friendly biorefinery process showed promising in maximizing the utilization of biomass for future biofuels production.

Biorefinery of corn cob for microbial lipid and bio-ethanol production: An environmental friendly process.

Microbial lipid and bio-ethanol were co-generated by an integrated process using corn cob bagasse as raw material. After pretreatment, the acid hydrolysate was used as substrate for microbial lipid fermentation, while the solid residue was further enzymatic hydrolysis for bio-ethanol production. The effect of acid loading and pretreatment time on microbial lipid and ethanol production were evaluated. Under the optimized condition for ethanol production, ∼131.3g of ethanol and ∼11.5g of microbial lipid were co-generated from 1kg raw material. On this condition, ∼71.6% of the overall fermentable sugars in corn cob bagasse could be converted into valuable products. At the same time, at least 33% of the initial COD in the acid hydrolysate was depredated.

Acetone-butanol-ethanol from sweet sorghum juice by an immobilized fermentation-gas stripping integration process.

In this study, sweet sorghum juice (SSJ) was used as the substrate in a simplified ABE fermentation-gas stripping integration process without nutrients supplementation. The sweet sorghum bagasse (SSB) after squeezing the fermentable juice was used as the immobilized carrier. The results indicated that the productivity of ABE fermentation process was improved by gas stripping integration. A total 24g/L of ABE solvents was obtained from 59.6g/L of initial sugar after 80h of fermentation with gas stripping. Then, long-term of fed-batch fermentation with continuous gas stripping was further performed. 112.9g/L of butanol, 44.1g/L of acetone, 9.5g/L of ethanol (total 166.5g/L of ABE) was produced in overall 312h of fermentation. At the same time, concentrated ABE product was obtained in the condensate of gas stripping.

Effect of dilute alkaline pretreatment on the conversion of different parts of corn stalk to fermentable sugars and its application in acetone-butanol-ethanol fermentation.

To investigate the effect of dilute alkaline pretreatment on different parts of biomass, corn stalk was separated into flower, leaf, cob, husk and stem, which were treated by NaOH in range of temperature and chemical loading. The NaOH-pretreated solid was then enzymatic hydrolysis and used as the substrate for batch acetone-butanol-ethanol (ABE) fermentation. The results demonstrated the five parts of corn stalk could be used as potential feedstock separately, with vivid performances in solvents production. Under the optimized conditions towards high product titer, 7.5g/L, 7.6g/L, 9.4g/L, 7g/L and 7.6g/L of butanol was obtained in the fermentation broth of flower, leaf, cob, husk and stem hydrolysate, respectively. Under the optimized conditions towards high product yield, 143.7g/kg, 126.3g/kg, 169.1g/kg, 107.7g/kg and 116.4g/kg of ABE solvent were generated, respectively.

Comparison of two-stage acid-alkali and alkali-acid pretreatments on enzymatic saccharification ability of the sweet sorghum fiber and their physicochemical characterizations.

Two-stage acid/alkali pretreatment was used to enhance the saccharification efficiency of sweet sorghum fiber. The physicochemical characterizations of the pretreated fibers were evaluated by SEM, FTIR and XRD. The acid and alkali sequence in the two-stage pretreatment process was compared, and their dosage was optimized. The results indicated that the two-stage pretreatment showed better saccharification performance when compared with conventional single stage pretreatment. And compared with the acid-alkali sequence, the alkali-acid sequence achieved higher glucose yield (0.23g·g-1) under the optimized conditions, which was 1.64 and 1.21 times higher than that of the single stage and the acid-alkali pretreatments, respectively. Overall, the two-stage pretreatment process is a promising approach to achieve high fermentable glucose conversion rate of cellulosic material.

Immobilized ethanol fermentation coupled to pervaporation with silicalite-1/polydimethylsiloxane/polyvinylidene fluoride composite membrane.

A novel silicalite-1/polydimethylsiloxane/polyvinylidene fluoride hybrid membrane was used in ethanol fermentation-pervaporation integration process. The sweet sorghum bagasse was used as the immobilized carrier. Compared with the conventional suspend cells system, the immobilized fermentation system could provide higher ethanol productivity when coupled with pervaporation. In the long-term of operations, the ethanol productivity, separation factor, total flux and permeate ethanol concentration in the fed-batch fermentation-pervaporation integration scenario were 1.6g/Lh, 8.2-9.9, 319-416g/m(2)h and 426.9-597.2g/L, respectively. Correspondingly, 1.6g/Lh, 7.8-9.8, 227.8-395g/m(2)h and 410.9-608.1g/L were achieved in the continuous fermentation-pervaporation integration scenario, respectively. The results indicated that the integration process could greatly improve the ethanol production and separation performances.

Effect of chemical pretreatments on corn stalk bagasse as immobilizing carrier of Clostridium acetobutylicum in the performance of a fermentation-pervaporation coupled system.

In this study, different pretreatment methods were evaluated for modified the corn stalk bagasse and further used the pretreated bagasse as immobilized carrier in acetone-butanol-ethanol fermentation process. Structural changes of the bagasses pretreated by different methods were analyzed by Fourier transform infrared, crystallinity index and scanning pictures by electron microscope. And the performances of batch fermentation using the corn stalk based carriers were evaluated. Results indicated that the highest ABE concentration of 23.86g/L was achieved using NaOH pretreated carrier in batch fermentation. Immobilized fermentation-pervaporation integration process was further carried out. The integration process showed long-term stability with 225-394g/L of ABE solvents on the permeate side of pervaporation membrane. This novel integration process was found to be an efficient method for biobutanol production.

Effect of acid pretreatment on different parts of corn stalk for second generation ethanol production.

In this study, the effects of different parts of corn stalk, including stem, leaf, flower, cob and husk on second generation ethanol production were evaluated. FTIR, XRD and SEM were performed to investigate the effect of dilute acid pretreatment. The bagasse obtained after pretreatment were further hydrolyzed by cellulase and used as the substrate for ethanol fermentation. As results, hemicelluloses fractions in different parts of corn stalk were dramatically removed and the solid fractions showed vivid compositions and crystallinities. Compared with other parts of corn stalk, the cob had higher sugar content and better enzymatic digestibility. The highest glucose yield of 94.2% and ethanol production of 24.0 g L(-1) were achieved when the cob was used as feedstock, while the glucose yield and the ethanol production were only 86.0% and 17.1 g L(-1) in the case of flower.