ExomiRHub: A comprehensive database for hosting and analyzing human disease-related extracellular microRNA transcriptomics data.

Extracellular microRNA (miRNA) expression data generated by different laboratories exhibit heterogeneity, which poses challenges for biologists without bioinformatics expertise. To address this, we introduce ExomiRHub (http://www.biomedical-web.com/exomirhub/), a user-friendly database designed for biologists. This database incorporates 191 human extracellular miRNA expression datasets associated with 112 disease phenotypes, 62 treatments, and 24 genotypes, encompassing 29,198 and 23 sample types. ExomiRHub also integrates 16,012 miRNA transcriptomes of 156 cancer subtypes from The Cancer Genome Atlas. All the data in ExomiRHub were further standardized and curated with annotations. The platform offers 25 analytical functions, including differential expression, co-expression, Weighted Gene Co-Expression Network Analysis (WGCNA), feature selection, and functional enrichment, enabling users to select samples, define groups, and customize parameters for analyses. Moreover, ExomiRHub provides a web service that allows biologists to analyze their uploaded miRNA expression data. Four additional tools were developed to evaluate the functions and targets of miRNAs and miRNA variations. Through ExomiRHub, we identified extracellular miRNA biomarkers associated with angiogenesis for monitoring glioma progression, demonstrating its potential to significantly accelerate the discovery of extracellular miRNA biomarkers.

Isolation of a novel feather-degrading Ectobacillus sp. JY-23 strain and characterization of a new keratinase in the M4 metalloprotease family.

Microbial keratinases have prominent potential in biotransformation of recalcitrant keratin substrates to value-added products which has made keratinases a research focus in the past decades. In this study, an efficient feather-degrading bacterium was isolated and identified as a novel species in Ectobacillus genus and designated as Ectobacillus sp. JY-23. The degradation characteristics analysis revealed that Ectobacillus sp. JY-23 could utilize chicken feathers (0.4% w/v) as the sole nutrient source and degraded 92.95% of feathers in 72 h. A significant increase in sulfite and free sulfydryl group content detected in the feather hydrolysate (culture supernatant) indicated efficient reduction of disulfide bonds, which inferred that the degradation mechanism of isolated strain was a synergetic action of sulfitolysis and proteolysis. Moreover, abundant amino acids were also detected, among which proline and glycine were the predominant free amino acids. Then, the keratinase of Ectobacillus sp. JY-23 was mined and Y1_15990 was identified as the keratinase encoding gene of Ectobacillus sp. JY-23 and designated as kerJY-23. Escherichia coli strain overexpressing kerJY-23 degraded chicken feathers in 48 h. Finally, bioinformatics prediction of KerJY-23 demonstrated that it belonged to the M4 metalloprotease family, which was a third keratinase member in this family. KerJY-23 showed low sequence identity to the other two keratinase members, indicating the novelty of KerJY-23. Overall, this study presents a novel feather-degrading bacterium and a new keratinase in the M4 metalloprotease family with remarkable potential in feather keratin valorization.

Reduced binding activity of vaccine serum to omicron receptor-binding domain.

Coronavirus disease 2019 (COVID-19) vaccination regimens contribute to limiting the spread of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). However, the emergence and rapid transmission of the SARS-CoV-2 variant Omicron raise a concern about the efficacy of the current vaccination strategy. Here, we expressed monomeric and dimeric receptor-binding domains (RBDs) of the spike protein of prototype SARS-CoV-2 and Omicron variant in E. coli and investigated the reactivity of anti-sera from Chinese subjects immunized with SARS-CoV-2 vaccines to these recombinant RBDs. In 106 human blood samples collected from 91 participants from Jiangxi, China, 26 sera were identified to be positive for SARS-CoV-2 spike protein antibodies by lateral flow dipstick (LFD) assays, which were enriched in the ones collected from day 7 to 1 month post-boost (87.0%) compared to those harvested within 1 week post-boost (23.8%) (P < 0.0001). A higher positive ratio was observed in the child group (40.8%) than adults (13.6%) (P = 0.0073). ELISA results showed that the binding activity of anti-SARS-CoV-2 antibody-positive sera to Omicron RBDs dropped by 1.48- to 2.07-fold compared to its homogeneous recombinant RBDs. Thus, our data indicate that current SARS-CoV-2 vaccines provide restricted humoral protection against the Omicron variant.

COVID19db: a comprehensive database platform to discover potential drugs and targets of COVID-19 at whole transcriptomic scale.

Many open access transcriptomic data of coronavirus disease 2019 (COVID-19) were generated, they have great heterogeneity and are difficult to analyze. To utilize these invaluable data for better understanding of COVID-19, additional software should be developed. Especially for researchers without bioinformatic skills, a user-friendly platform is mandatory. We developed the COVID19db platform (http://hpcc.siat.ac.cn/covid19db & http://www.biomedical-web.com/covid19db) that provides 39 930 drug-target-pathway interactions and 95 COVID-19 related datasets, which include transcriptomes of 4127 human samples across 13 body sites associated with the exposure of 33 microbes and 33 drugs/agents. To facilitate data application, each dataset was standardized and annotated with rich clinical information. The platform further provides 14 different analytical applications to analyze various mechanisms underlying COVID-19. Moreover, the 14 applications enable researchers to customize grouping and setting for different analyses and allow them to perform analyses using their own data. Furthermore, a Drug Discovery tool is designed to identify potential drugs and targets at whole transcriptomic scale. For proof of concept, we used COVID19db and identified multiple potential drugs and targets for COVID-19. In summary, COVID19db provides user-friendly web interfaces to freely analyze, download data, and submit new data for further integration, it can accelerate the identification of effective strategies against COVID-19.

circMine: a comprehensive database to integrate, analyze and visualize human disease-related circRNA transcriptome.

Many circRNA transcriptome data were deposited in public resources, but these data show great heterogeneity. Researchers without bioinformatics skills have difficulty in investigating these invaluable data or their own data. Here, we specifically designed circMine (http://hpcc.siat.ac.cn/circmine and http://www.biomedical-web.com/circmine/) that provides 1 821 448 entries formed by 136 871 circRNAs, 87 diseases and 120 circRNA transcriptome datasets of 1107 samples across 31 human body sites. circMine further provides 13 online analytical functions to comprehensively investigate these datasets to evaluate the clinical and biological significance of circRNA. To improve the data applicability, each dataset was standardized and annotated with relevant clinical information. All of the 13 analytic functions allow users to group samples based on their clinical data and assign different parameters for different analyses, and enable them to perform these analyses using their own circRNA transcriptomes. Moreover, three additional tools were developed in circMine to systematically discover the circRNA-miRNA interaction and circRNA translatability. For example, we systematically discovered five potential translatable circRNAs associated with prostate cancer progression using circMine. In summary, circMine provides user-friendly web interfaces to browse, search, analyze and download data freely, and submit new data for further integration, and it can be an important resource to discover significant circRNA in different diseases.

Effect of bioaugmentation on lignocellulose degradation and antibiotic resistance genes removal during biogas residues composting.

In this study, six strains belonging to Alcaligenes, Enterobacter and Bacillus were employed to enhance the composting process of biogas residues and agricultural wastes. The dynamic changes of dissolved organic matter (DOM), microbial community and functional genes in composting was monitored. It was found bioaugmentation reduced the content of lignocellulose in the compost by 27.14-66.30%, and increased the seed germination index (GI) of the compost by 37.59%. Metagenomics analysis of the composting process indicated Proteobacteria (35.38%-64.19%), Actinobacteria (11.24%-28.93%) and Bacteroidetes (3.65%-9.57%) are the dominant microorganisms during the bioaugmented composting. The abundance of genes associated with glycoside hydrolase was obviously enhanced and the antibiotic resistance genes (ARGs) was significantly reduced during the bioaugmented composting. Following nursery investigation indicated the seedling substrates composed of bioaugmented compost increased the dry weight of tomato seedlings by 1.7 times, revealing obvious large-scale application potential in the resource utilization of agricultural wastes.

Detoxification of azo dye Direct Black G by thermophilic Anoxybacillus sp. PDR2 and its application potential in bioremediation.

Direct Black G (DBG) is a highly toxic synthetic azo dye which is difficult to degrade. Biological treatment seems to be a promising option for the treatment of azo dye containing effluent. A thermophilic bacterial strain (Anoxybacillus sp. PDR2) previously isolated from the soil can effectively remove DBG. However, the molecular underpinnings of DBG degradation and the microbial detoxification ability remains unknown. In the present study, the genetic background of PDR2 for the efficient degradation of DBG and its adaptation to azo dye-contaminated environments was revealed by bioinformatics. Moreover, the possible biodegradation pathways were speculated based on the UV-vis spectral analysis, FTIR, and intermediates identified by LC-MS. Additionally, phytotoxicity and the comet experiment studies clearly indicated that PDR2 converts toxic azo dye (DBG) into low toxicity metabolites. The combination of biodegradation pathways and detoxification analysis were utilized to explore the molecular degradation mechanism and bioremediation of azo dye for future applications. These findings will provide a valuable theoretical basis for the practical treatment of azo dye wastewater.

Cellulolytic bacterium characterization and genome functional analysis: An attempt to lay the foundation for waste management.

Lignocellulosic waste has offered a cost-effective and food security-wise substrate for the generation of biofuels and value-added products. Here, whole-genome sequencing and comparative genomic analyses were performed for Serratia sp. AXJ-M. The results showed that strain AXJ-M contained a high proportion of strain-specific genes related to carbohydrate metabolism. Furthermore, the genetic basis of strain AXJ-M for efficient degradation of cellulose was identified. Cellulase activity tests revealed strong cellulose degradation ability and cellulase activities in strain AXJ-M. mRNA expression indicated that GH1, GH3 and GH8 might determine the strain's cellulose degradation ability. The SWISS-MODEL and Ramachandran Plot were used to predict and evaluate the 3D structure, respectively. High performance liquid chromatography (HPLC) and gas chromatography-mass spectrometer (GC-MS) were used to analyze the cellulose degradation products. Further research is needed to elucidate the cellulose degradation mechanism and to develop industrial applications for lignocellulosic biomass degradation and waste management.

Evaluation of bioremediation and detoxification potentiality for papermaking black liquor by a new isolated thermophilic and alkali-tolerant Serratia sp. AXJ-M.

There is a great need for efficiently treating papermaking black liquor because it can seriously pollute both soil and water ecosystems. In this study, the Plackett-Burman (PB) experimental design combined with response surface methodology (RSM) was used for improving the biodegradation efficiency of lignin by a new isolated thermophilic and alkali-tolerant strain Serratia sp. AXJ-M, and the results showed that a biodegradation efficiency of 70.5% was achieved under optimal culture conditions. The bacterium with ligninolytic activities significantly decreased target the parameters (color 80%, lignin 60%, phenol 95%, BOD 80% and COD 80%). The control and treated samples were analyzed by gas chromatography-mass spectrometer (GC-MS), which showed that the concentrations of a majority of low-molecular-weight compounds were decreased after biological treatment. Furthermore, toxicological, genotoxicity and phytotoxicity studies have supported the detoxification by the bacterium of black liquor. Finally, the genome sequence of the thermophilic, alkali-tolerant and lignin-degrading bacterium AXJ-M was completed, and the genetic basis of the thermophilic and alkali-resistant properties of AXJ-M was preliminarily revealed. The dyp-type peroxidase was first reported to have the potential to catalyze lignin degradation structurally. These findings suggest that Serratia sp. AXJ-M may be potentially useful for bioremediation applications for papermaking black liquor.

Acetone, butanol, and ethanol production from puerariae slag hydrolysate through ultrasound-assisted dilute acid by Clostridium beijerinckii YBS3.

In this study, puerariae slag (PS) was evaluated as a renewable raw material for acetone-butanol-ethanol (ABE) fermentation. To accelerate the hydrolysis of PS, the method of ultrasound-assisted dilute acid hydrolysis (UAAH) was used. With this effort, 0.69 g reducing sugar was obtained from 1 g raw material under the optimal pretreatment condition. Subsequently, the butanol and total solvent production of 8.79 ± 0.16 g/L and 12.32 ± 0.26 g/L were obtained from the non-detoxified diluted hydrolysate, and the yield and productivity of butanol were 0.19 g/g and 0.12 g/L/h, respectively. Additionally, the changes in the structure of PS after different pretreatment methods were observed using SEM and FT-IR. UAAH resulted in more severe and distinct damage to the dense structure of PS. This study suggests that the UAAH is an attainable but effective pretreatment method, thereby is a promising technique for lignocellulose hydrolysis and improve butanol production.

All-Optical Tuning of Light in WSe2-Coated Microfiber.

The tungsten diselenide (WSe2) has attracted considerable interest owing to their versatile applications, such as p-n junctions, transistors, fiber lasers, spintronics, and conversion of solar energy into electricity. We demonstrate all-optical tuning of light in WSe2-coated microfiber (MF) using WSe2's broad absorption bandwidth and thermo-optic effect. The transmitted optical power (TOP) can be tuned using external incidence pump lasers (405, 532, and 660 nm). The sensitivity under 405-nm pump light excitation is 0.30 dB/mW. A rise/fall time of ~ 15.3/16.9 ms is achieved under 532-nm pump light excitation. Theoretical simulations are performed to investigate the tuning mechanism of TOP. The advantages of this device are easy fabrication, all-optical control, high sensitivity, and fast response. The proposed all-optical tunable device has potential applications in all-optical circuitry, all-optical modulator, and multi-dimensionally tunable optical devices, etc.

Broadband all-light-control with WS2 coated microfibers.

All-optical light amplitude tuning functionality is demonstrated in a layered tungsten disulfide (WS2) nanosheets coated microfiber (MF) structure. Due to the strong light-matter interactions between WS2 nanosheets and the evanescent field around the MF, a large variation in the transmitted power can be observed under both external and internal pump light excitations over a broadband spectrum (~100 nm). A power variation rate of ~0.3744 dB/mW is obtained under external violet pump light excitation, whereas the power variation rate of similar devices in the state of the art are usually less than 0.3 dB/mW. In terms of the response time, a moderate rise/fall time of ∼20.5/19.6 ms is achieved, which is mainly limited by the employed structure fabrication methods. These results indicate that the optical transmitted power of the WS2 coated MF can be modulated by different pump light with the power in the order of mW, thus the proposed device might have potential applications in all optical controllable devices and sensors, etc.

Highly sensitive all-optical control of light in WS2 coated microfiber knot resonator.

All-optical light-control-light functionality is realized in a layered tungsten disulfide (WS2) nanosheet coated microfiber knot resonator (MKR) structure. Mainly due to the photon generated excitons induced refractive index variation in WS2 nanosheets, a large variation in the transmitted power (∆T) can be observed under external violet/red laser excitation. The ∆T variation rates can reach up to ~0.4 dB/mW under violet pump light excitation whereas the state of the art light-control-light structures usually has a variation rate of less than 0.25 dB/mW. In terms of the response time, the averaged rise/fall time is ~0.12/0.1 s. The demonstrated structure has the advantages of easy fabrication, low cost and high sensitivity, therefore, it might be a promising candidate for building future all-fiber-optics based functional devices and all-optical circuitry.

Effect of organic loading rate on anaerobic co-digestion of rice straw and pig manure with or without biological pretreatment.

In this study, rice straw (RS) and pig manure (PM) mixtures with or without bio-pretreatment were used as the substrates and digested in a 9 L of anaerobic reactor at Organic loading rates (OLRs) of 0.4-3.1 kg COD/(m3 d). The volumetric methane production rate (VMPR), methane yield and anaerobic stability were comparatively investigated. The results showed the co-anaerobic digestion processes of RS and PM mixture after biological pretreatment were very stable at OLRs of 0.4-2.5 kg COD/(m3 d), and its optimal VMPR and methane yield could reach 0.64 L CH4/(L d) and 0.4557 L CH4/g CODremoved at OLR of 2.5 kg COD/(m3 d), which were 62.4% and 37.8% higher than those of the control under the same OLR condition. This study indicated the biological pretreatment with a cellulolytic microbial consortium own great potential in improving the methane yield and productivity of RS and PM wastes.

Biodegradation and detoxification of Direct Black G textile dye by a newly isolated thermophilic microflora.

The biodegradation and detoxification of azo dye - Direct Black G (DBG) with a newly isolated thermophilic microflora was investigated in the present study. It was found this microflora can decolorize DBG at a wide range of pH from 5 to 10, and grow well under high concentration of dye (600 mg·L-1) and salinity (50 g·L-1). Its decolorization ratio could reach 97% with 8 h of incubation at optimal conditions. The induction of laccase, manganese peroxidase, lignin peroxidase and azoreductase suggests their synergetic involvements in the degradation process of DBG. In addition, the phytotoxicity analysis indicated the thermophilic microflora converted toxic dye DBG into low toxicity metabolites. PCR-DGGE analysis revealed that there are nine different bacteria presented in this microflora. Furthermore, a new degradation pathway of DBG degradation by this microflora was proposed based on the intermediates identified by LC-ESI-MS/MS.

Enhanced butanol production by solvent tolerance Clostridium acetobutylicum SE25 from cassava flour in a fibrous bed bioreactor.

To enhance the butanol productivity and reduce the material cost, acetone, butanol, and ethanol fermentation by Clostridium acetobutylicum SE25 was investigated using batch, repeated-batch and continuous cultures in a fibrous bed bioreactor, where cassava flour was used as the substrate. With periodical nutrient supplementation, stable butanol production was maintained for about 360h in a 6-cycle repeated-batch fermentation with an average butanol productivity of 0.28g/L/h and butanol yield of 0.32g/g-starch. In addition, the highest butanol productivity of 0.63g/L/h and butanol yield of 0.36g/g-starch were achieved when the dilution rate were investigated in continuous production of acetone, butanol, and ethanol using a fibrous bed bioreactor, which were 231.6% and 28.6% higher than those of the free-cell fermentation. On the other hand, this study also successfully comfirmed that the biofilm can provide an effective protection for the microbial cells which are growing in stressful environment.

Nutrient Optimization Using Response Surface Methodology for Simultaneous Biomass and Bioactive Compound Production by Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes).

Due to the unpleasant side effects of long-term use of commercially available drugs, the discovery and development of natural therapeutic agents to prevent life-debilitating diseases is urgently needed. In the present study, the optimization of medium composition for maximum mycelial biomass and bioactive compounds production by Hericium erinaceus was studied using response surface methodology based on a central composite design. Under the optimal conditions and at a pH of 5.41 ± 0.28, the maximum mycelial biomass and exopolysaccharide production reached 25.0 ± 1.38 g/L and 1.73 ± 0.06 g/L, respectively, compared with 22.65 ± 0.10 g/L and 1.56 ± 0.23 g/L in the basal medium, after 7 days of cultivation. Furthermore, we report for the first time the production of adenosine, both intra- and extracellularly in submerged cultures of H. erinaceus. Although most of the adenosine detected existed in the culture medium, the highest intracellular and extracellular adenosine concentrations of 150.84 ± 1.87 mg/L and 142.48 ± 3.78 mg/L were achieved after 7 and 6 days of cultivation, respectively.

Exploration of the key functional proteins from an efficient cellulolytic microbial consortium using dilution-to-extinction approach.

In the present study, the cellulose binding proteins (CBPs) secreted by a putative cellulolytic microbial consortium were isolated and purified by affinity digestion. The purified CBPs were subsequently separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Using mass spectrometric analyses, eight CBPs were identified and annotated to be similar to known proteins secreted by Clostridium clariflavum DSM 19732 and Paenibacillus sp. W-61. In addition, in combination with dilution-to-extinction approach and zymogram analysis technique, CBPs 6 (97kDa) and 12 (52kDa) were confirmed to be the key functional proteins that influence cellulolytic activities. Moreover, structural domain analyses and enzymatic activity detection indicated that CBPs 6 and 12 contained glycoside hydrolase families (GH) 9 and 48 catalytic modules, which both revealed endoglucandase and xylanase activities. It was suggested that the coexistence of GH9 and GH48 catalytic domains present in these two proteins could synergistically promote the efficient degradation of cellulose.

Enhancement of butanol production in Clostridium acetobutylicum SE25 through accelerating phase shift by different phases pH regulation from cassava flour.

A prominent delay with 12h was encountered in the phase shift from acidogenesis to solventogenesis in butanol production when the substrate-glucose was replaced by cassava flour. To solve this problem, different phase of pH regulation strategies were performed to shorten this delay time. With this effort, the phase shift occurred smoothly and the fermentation time was shortened. Under the optimal conditions, 16.24g/L butanol and 72h fermentation time were achieved, which were 25.3% higher and 14.3% shorter than those in the case of without pH regulation. Additionally, the effect of CaCO3 on "acid crash" and butanol production was also investigated. It was found that organic acids reassimilation would be of benefit to enhance butanol production. These results indicated that the simple but effective approach for acceleration of phase shift is a promising technique for shortening the fermentation time and improvement of butanol production.

Effect of inoculation process on lycopene production by Blakeslea trispora in a stirred-tank reactor.

Lycopene biosynthesis by Blakeslea trispora was greatly enhanced in a stirred-tank reactor when a nonsynchronous inoculation process, in which the (+) mating type was inoculated after the (-) mating type has been grown for a certain period of time, was applied. The lycopene concentration with nonsynchronous inoculation in a 24-h inoculation interval was 33 % higher than that with synchronous inoculation. The optimum inoculation ratio was 1:2 (+/-) at the 36 and 48 h inoculum age of mating types (+) and (-), respectively. Fermentation time for the individual strains and mated conditions showed that the (+) mating type grows faster than the (-) mating type. Morphological observation showed that the mycelium ratio of B. trispora (-) in mating culture with nonsynchronous inoculation was higher than that with synchronous inoculation. The results indicated that nonsynchronous inoculation process increased the dominance of B. trispora (-) in joint cultivation and hence stimulated lycopene biosynthesis.