Close-packed nitronyl nitroxide radicals by Au-S self-assembly: strong ferromagnetic coupling.

The study of the magnetism of tightly arranged nitronyl nitroxide (NN) radicals via Au-S self-assembly is interesting. In this study, a series of radicals (S-NN, D-NN, BS-NN, BD-NN) along with two types of nanomaterials (S-NPs, D-NPs) were synthesized. NN was chosen for the magnetic units. Their structures have been successfully synthesized and analyzed. The spin magnetic properties were characterized by electron paramagnetic resonance (EPR) and superconducting quantum interference device (SQUID) measurement. The analysis revealed that the self-assembled NN formed via Au-S bonds exhibits high packing density. Furthermore, it was gratifying to observe that the AuNPs exhibit ferromagnetism after the surface modification by NN. This results in strong ferromagnetic exchange interactions of S-NPs and D-NPs : J S-NPs = +279.715 K and J D-NPs = +254.913 K, respectively.

Differential effects of polystyrene microplastics on the adsorption of cadmium and ciprofloxacin by tea leaf litter-derived magnetic biochar: Influencing factors and mechanisms.

Water pollution involves the coexistence of microplastics (MPs) and traditional pollutants, and how can MPs influence the adsorption of other pollutants by biochar during the treatment process remains unclear. This study aimed to investigate the influence of polystyrene microplastics (PS MPs) on the adsorption of cadmium (Cd) and ciprofloxacin (CIP) by magnetic biochar (MTBC) in the single and binary systems. MTBC was prepared using tea leaf litter; the effects of time, pH, and salt ions on the adsorption behaviors were investigated; and X-ray photoelectronic spectroscopy (XPS) and density flooding theory analysis were conducted to elucidate the influence mechanisms. Results indicated that PS MPs reduced the pollutants adsorption by MTBC due to the heterogeneous aggregation between PS MPs and MTBC and the surface charge change of MTBC induced by PS MPs. The effects of PS MPs on heavy metals and antibiotics adsorption were distinctly different. PS MPs reduced Cd adsorption on MTBC, which were significantly influenced by the solution pH and salt ions contents, suggesting the participation of electrostatic interaction and ion exchange in the adsorption, whereas the effects of PS MPs on CIP adsorption were inconspicuous. In the hybrid system, PS MPs reduced pollutants adsorption by MTBC with 66.3% decrease for Cd and 12.8% decrease for CIP, and the more remarkable reduction for Cd was due to the predominated physical adsorption, and CIP adsorption was mainly a stable chemisorption. The influence of PS MPs could be resulted from the interaction between PS MPs and MTBC with changing the functional groups and electrostatic potential of MTBC. This study demonstrated that when using biochar to decontaminate wastewater, it is imperative to consider the antagonistic action of MPs, especially for heavy metal removal. PRACTITIONER POINTS: Magnetic biochar (MTBC) was prepared successfully using tea leaf litter. MTBC could be used for cadmium (Cd) and ciprofloxacin (CIP) removal. Polystyrene microplastics (Ps MPs) reduced Cd/CIP adsorption by MTBC. Ps MPs effects on Cd adsorption were more obvious than that of CIP. Ps MPs changed the functional groups and electrostatic potential of MTBC, thus influencing MTBC adsorption.

Boron Neutron Capture Therapy-Derived Extracellular Vesicles via DNA Accumulation Boost Antitumor Dendritic Cell Vaccine Efficacy.

Radiated tumor cell-derived extracellular vesicles (RT-EVs) encapsulate abundant DNA fragments from irradiated tumor cells, in addition to acting as integrators of multiple tumor antigens. Accumulating evidence indicates these DNA fragments from damaged cells are involved in downstream immune responses, but most of them are degraded in cells before incorporation into derived RT-EVs, thus the low abundance of DNA fragments limits immune responses of RT-EVs. Here, this study found that different radiations affected fates of DNA fragments in RT-EVs. Boron neutron capture therapy (BNCT) induced DNA accumulation in RT-EVs (BEVs) by causing more DNA breaks and DNA oxidation resisting nuclease degradation. This is attributed to the high-linear energy transfer (LET) properties of alpha particles from the neutron capture reaction of 10B. When being internalized by dendritic cells (DCs), BEVs activated the DNA sensing pathway, resulting in functional enhancements including antigen presentation, migration capacity, and cytokine secretion. After vaccination of the BEVs-educated DCs (BEV@BMDCs), the effector T cells significantly expanded and infiltrated into tumors, suggesting robust anti-tumor immune activation. BEV@BMDCs not only effectively inhibited the primary tumor growth and metastasis formation but also elicited long-term immune memory. In conclusion, a successful DC vaccine is provided as a promising candidate for tumor vaccine.

Effect of Composition Characteristics on Mechanical Properties of UHPMC Based on Response Surface Methodology and Acoustic Emission Monitoring.

Manufactured sand (MS) is a promising alternative aggregate to quartz sand (QS) in ultra-high-performance concrete (UHPC) in the preparation of ultra-high-performance manufactured sand concrete (UHPMC), which possesses the characteristics of high strength, low cost, and environmental friendliness. In this study, the effects of variable compositional characteristics including the water-binder ratio, the stone powder (SP) content, and the MS replacement ratio on the mechanical and flexural strength of UHPMC were compared and analyzed based on response surface methodology (RSM). Meanwhile, the damage characteristics of UHPMC during compressive and flexural stress were monitored and evaluated using acoustic emission (AE) technology. The results reveal that the compressive and flexural strengths of UHPMC are both negatively correlated with the water-binder ratio, while they are positively correlated with the MS replacement rate. They tend to firstly increase and subsequently decrease with the increase in the stone powder content. In the load-displacement curve of concrete with a high MS replacement ratio and a low water-binder ratio, the slope in the elastic stage is steeper, the stiffness is higher, and the bending toughness and ductility are also better. The specimens with a 10% to 0% stone powder content present a steeper elastic phase slope, a slightly higher stiffness, and superior ductility. The specimens with a low MS replacement ratio and a high water-binder ratio display earlier cracking and weaker resistance, and the destruction process is complex and very unstable. The damage mode analysis based on RA-AF shows that an increase in the MS replacement ratio and a decrease in the water-binder ratio can both reduce the tensile cracking of UHPMC specimens under a four-point bending test. Although 10% stone powder can marginally slow down crack growth, the failure mode is not significantly affected.

Study of Molecular Dimer Morphology Based on Organic Spin Centers: Nitronyl Nitroxide Radicals.

In this work, in order to investigate the short-range interactions between molecules, the spin-magnetic unit nitronyl nitroxide (NN) was introduced to synthesize self-assembly single radical molecules with hydrogen bond donors and acceptors. The structures and magnetic properties were extensively investigated and characterized by UV-Vis absorption spectroscopy, electron paramagnetic resonance (EPR), and superconducting quantum interference devices (SQUIDs). Interestingly, it was observed that the single molecules can form two different dimers (ring-closed dimer and "L"-type dimer) in different solvents, due to hydrogen bonding, when using EPR to track the molecular spin interactions. Both dimers exhibit ferromagnetic properties (for ring-closed dimer, J/kB = 0.18 K and ΔES-T = 0.0071 kcal/mol; for "L"-type dimer, the values were J/kB = 9.26 K and ΔES-T = 0.037 kcal/mol). In addition, the morphologies of the fibers formed by the two dimers were characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM).

Hexanoic acid production and microbial community in anaerobic fermentation: Effects of inorganic carbon addition.

Carbon dioxide (CO2) plays a crucial role in carbon chain elongation with ethanol serving as an electron donor. In this study, the impacts of various carbonates on CO2 concentration, hexanoic acid production, and microbial communities during ethanol-butyric acid fermentation were explored. The results showed that the addition of MgCO3 provided sustained inorganic carbon and facilitated interspecific electron transfer, thereby increasing hexanoic acid yield by 58%. MgCO3 and NH4HCO3 inhibited the excessive ethanol oxidation and decreased the yield of acetic acid by 51% and 42%, respectively. The yields of hexanoic acid and acetic acid in the CaCO3 group increased by 19% and 15%, respectively. The NaHCO3 group exhibited high headspace CO2 concentration, promoting acetogenic bacteria enrichment while reducing the abundance of Clostridium_sensu_stricto_12. The batch addition of NaHCO3 accelerated the synthesis of hexanoic acid and increased its production by 26%. The relative abundance of Clostridium_sensus_stricto_12 was positively correlated with hexanoic acid production.

Boron-Containing Mesoporous Silica Nanoparticles with Effective Delivery and Targeting of Liver Cancer Cells for Boron Neutron Capture Therapy.

Nanocarriers have been researched comprehensively for the development of novel boron-containing agents in boron neutron capture therapy (BNCT). We designed and synthesized a multifunctional mesoporous silica nanoparticle (MSN)-based boron-containing agent. The latter was coated with a lipid bilayer (LB) and decorated with SP94 peptide (SFSIIHTPILPL) on the surface as SP94-LB@BA-MSN. The latter incorporated boric acid (BA) into hydrophobic mesopores, coated with an LB, and modified with SP94 peptide on the LB. SP94-LB@BA-MSN enhanced nano interface tumor-targeting ability but also prevented the premature release of drugs, which is crucial for BNCT because adequate boron content in tumor sites is required. SP94-LB@BA-MSN showed excellent efficacy in the BNCT treatment of HepG-2 cells. In animal studies with tumor-bearing mice, SP94-LB@BA-MSN exhibited a satisfactory accumulation at the tumor site. The boron content reached 40.18 ± 5.41 ppm in the tumor site 4 h after injection, which was 8.12 and 15.51 times higher than those in mice treated with boronated phenylalanine and those treated with BA. For boron, the tumor-to-normal tissue ratio was 4.41 ± 1.13 and the tumor-to-blood ratio was 5.92 ± 0.45. These results indicated that nanoparticles delivered boron to the tumor site effectively while minimizing accumulation in normal tissues. In conclusion, this composite (SP94-LB@BA-MSN) shows great promise as a boron-containing delivery agent for the treatment of hepatocellular carcinoma using BNCT. These findings highlight the potential of MSNs in the field of BNCT.

Effects of yeast inoculation methods on caproic acid production and microbial community during anaerobic fermentation of Chinese cabbage waste.

To provide a sufficient supply of electron donors for the synthesis of caproic acid, yeast fermentation was employed to increase ethanol production in the anaerobic fermentation of Chinese cabbage waste (CCW). The results showed that the caproic acid yield of CCW with ethanol pre-fermentation was 7750.3 mg COD/L, accounting for 50.2% of the total volatile fatty acids (TVFAs), which was 32.5% higher than that of the CCW without yeast inoculation. The synchronous fermentation of yeast and seed sludge significantly promoted the growth of butyric acid consuming bacterium Bacteroides, resulting in low yields of butyric acid and caproic acid. With yeast inoculation, substrate competition for the efficient ethanol conversion in the early stage of acidogenic fermentation inhibited the hydrolysis and acidfication. Without yeast inoculation, the rapid accumulation of TVFAs severely inhibited the growth of Bacteroidetes. In the reactor with ethanol pre-fermentation, the key microorganism for caproic acid production, Clostridium_sensu_stricto_12, was selectively enriched.

Application of recombinase polymerase amplification with CRISPR/Cas12a and multienzyme isothermal rapid amplification with lateral flow dipstick assay for Bactrocera correcta.

BACKGROUND: Bactrocera correcta is a quarantine pest that negatively impacts the fruit and vegetable industry. Differentiating B. correcta from similar species, especially in non-adult stages, remains challenging. Rapid molecular identification techniques, such as recombinase polymerase amplification (RPA) combined with CRISPR/Cas12a and multienzyme isothermal rapid amplification with lateral flow dipstick (MIRA-LFD), play a crucial role in early monitoring and safeguarding agricultural production. Our study introduces two methods for the rapid visual identification of B. correcta. RESULTS: Bactrocera correcta specific RPA primers, CRISPR RNA (crRNA), and the LFD probe were designed based on the cox1 genes. The RPA reaction conditions were optimized (at 37 °C for 8 min) for effective template DNA amplification. Two nucleic acid detection methods were established to visualize RPA. In the RPA-CRISPR/Cas12a system, the optimal LbCas12a/crRNA concentration ratio was 200:400 nmol L-1. Successful amplification was determined by the presence or absence of green fluorescence following 15 min incubation at 37 °C. The MIRA-LFD system achieved precise identification of the target species within 4 min at 37 °C. Both methods exhibited high specificity and sensitivity, allowing for detection from 1.0 × 10-1 ng µL-1 of DNA. Combined with rapid DNA extraction, rapid identification of individual B. correcta at different developmental stages was achieved, enhancing the practicality and convenience of the established methods. CONCLUSION: Our research findings demonstrate that both the RPA-CRISPR/Cas12a and MIRA-LFD methods for B. correcta detection was accurate and rapid (within 30 min and 10 min, respectively), at 37 °C. Our methods do not rely on expensive equipment, thus possess high practical value, providing improved identification solutions for port quarantine pests and field applications. © 2024 Society of Chemical Industry.

Regulation of hydraulic retention time on caproic acid production via two-phase anaerobic fermentation of Chinese cabbage waste with autopoietic electron donors.

The effects of hydraulic retention time (HRT) on the performance of two-phase anaerobic fermentation for caproic acid production from Chinese cabbage waste (CCW) were investigated. In the electron donor phase, yeast was inoculated to achieve efficient autopoietic ethanol, providing electron donors for the chain elongation process. Shorter HRT led to drastic fluctuations in microorganisms, thus resulting in lower acid yields at HRT of 6 days. At HRT of 10 days, the balanced collaboration of various key bacteria avoided the accumulation of intermediate by-products, and the caproic acid production reached 4660 mg COD/L, which was 119.5% and 154.8% higher than that at HRTs of 6 and 14 days, respectively. At HRT of 14 days, the low ethanol loading rate resulted in ethanol excessive-oxidation to acetic acid. Acetic acid accounted for 41.5% of the total product, while the selectivity of caproic acid was only 15.3%. The main contributor to the production process of caproic acid was Caproiciproducens, while the Ruminalococcaceae also played a role in the process. This study provided a theoretical basis for the efficient production of caproic acid through continuous fermentation with autopoietic electron donors.

The transporter PHO84/NtPT1 is a target of aluminum to affect phosphorus absorption in Saccharomyces cerevisiae and Nicotiana tabacum L.

The molecular mechanism of aluminum toxicity in biological systems is not completely understood. Saccharomyces cerevisiae is one of the most used model organisms in the study of environmental metal toxicity. Using an unbiased metallomic approach in yeast, we found that aluminum treatment caused phosphorus deprivation, and the lack of phosphorus increased as the pH of the environment decreased compared to the control strain. By screening the phosphate signaling and response pathway (PHO pathway) in yeast with the synthetic lethality of a new phosphorus-restricted aluminum-sensitive gene, we observed that pho84Δ mutation conferred severe growth defect to aluminum under low-phosphorus conditions, and the addition of phosphate alleviated this sensitivity. Subsequently, the data showed that PHO84 determined the intracellular aluminum-induced phosphorus deficiency, and the expression of PHO84 was positively correlated with aluminum stress, which was mediated by phosphorus through the coordinated regulation of PHO4/PHO2. Moreover, aluminum reduced phosphorus absorption and inhibited tobacco plant growth in acidic media. In addition, the high-affinity phosphate transporter NtPT1 in tobacco exhibited similar effects to PHO84, and overexpression of NtPT1 conferred aluminum resistance in yeast cells. Taken together, positive feedback regulation of the PHO pathway centered on the high-affinity phosphate transporters is a highly conservative mechanism in response to aluminum toxicity. The results may provide a basis for aluminum-resistant microorganisms or plant engineering and acidic soil treatment.

Treatment of phenolic wastewater by anaerobic fluidized bed microbial fuel cell using carbon brush as anode: microbial community analysis and m-cresol degradation mechanism.

Anaerobic fluidized bed microbial fuel cell (AFB-MFC) is a technology that combines fluidized bed reactor and microbial fuel cell to treat organic wastewater and generate electricity. The performance and the mechanism of treating m-cresol wastewater in AFB-MFC using carbon brush as biofilm anode were studied. After 48 h of operation, the m-cresol removal efficiency of AFB-MFC, MAR-AFB (fluidized bed bioreactor with acclimated anaerobic sludge), MAR-FB (ordinary fluidized bed reactor with only macroporous adsorptive resin) and AST (traditional anaerobic sludge treatment) were 95.29 ± 0.67%, 85.78 ± 1.81%, 71.24 ± 1.86% and 70.41 ± 0.32% respectively. The maximum output voltage and the maximum power density of AFB-MFC using carbon brush as biofilm anode were 679.7 mV and 166.6 mW/m2 respectively. The results of high-throughput sequencing analysis indicated the relative abundance of dominant electroactive bacteria, such as Trichococcus, Geobacter, and Pseudomonas, on the anode carbon brushes was higher than that of AST, and also identified such superior m-cresol-degrading bacteria as Bdellovibrio, Thermomonas, Hydrogenophaga, etc. Based on the determination of m-cresol metabolites detected by Gas Chromatography-Mass Spectrometry (GC-MS), the possible biodegradation pathway of m-cresol under anaerobic and aerobic conditions in AFB-MFC was speculated. The results showed that m-cresol was decomposed into formic acid-acetic anhydride and 3-methylpropionic acid under the action of electrochemistry, which is a simple degradation pathway without peripheral metabolism in AFB-MFC.

Quarantine Disinfestation of Papaya Mealybug, Paracoccus marginatus (Hemiptera: Pseudococcidae) Using Gamma and X-rays Irradiation.

Paracoccus marginatus is a highly polyphagous invasive pest that poses a significant quarantine threat to tropical and subtropical countries. Infested commodities in international trade should undergo phytosanitary treatment, and irradiation is recommended as a viable alternative to replace methyl bromide fumigation. Dose-response tests were conducted on the 2-, 4-, and 6-day-old eggs and gravid females of P. marginatus using the X-ray radiation doses of 15-105 Gy with an interval of 15 Gy. Radiotolerance was compared using ANOVA, fiducial overlapping and lethal dose ratio (LDR) test, resulting in no significant difference among treatments, except for the overall mortality and LDR at LD90 (a dose causing 90% mortality at 95% confidence level). The estimated dose for LD99.9968 was 176.5-185.2 Gy, which was validated in the confirmatory tests. No nymphs emerged from a total of 60,386 gravid females exposed to a gamma radiation dose range of 146.8-185.0 Gy in the confirmatory tests. The largest dose in confirmatory tests should be the minimum threshold for phytosanitary treatment, consequently, a minimum dose of 185 Gy is recommended for the phytosanitary irradiation treatment of papaya mealybug-infested commodities, ensuring a treatment efficacy of ≥99.9950% at 95% confidence level.

Acidogenic fermentation of potato peel waste for volatile fatty acids production: Effect of initial organic load.

As a renewable carbon source produced from organic wastes by acidogenic fermentation, volatile fatty acids (VFAs) are important intermediates in chemical and biological fields and beneficial to resource recovery and carbon neutrality. Maximizing VFA production by some strategies without additional chemicals is critical to increasing economic and environmental benefits. In this study, the effects of initial organic load (OL) on the performance of VFA production, variations of intermediate metabolites, and the thermogravimetric properties of potato peel waste (PPW) during batch acidogenic fermentation were studied. The results showed that the concentration of VFAs increased with the increase of initial OL, while the VFA yield decreased with the increase of initial OL. When the initial OL was in the range of 28.4 g VS/L-91.3 g VS/L, the fermentation type of PPW was butyric acid fermentation. The highest butyric acid proportion of 61.3% was achieved with the initial OL of 71.5 g VS/L. With the increase of initial OL, the proportion of acetic acid and the utilization rate of protein in the PPW decreased. VFAs were produced from proteins and carbohydrates in the early stage and mainly produced from carbohydrates in the later stage. The production efficiency of VFA was relatively high with the initial OL of 71.5 g VS/L, because more easily-biodegradable compounds were solubilized. The results showed that suitably increased initial OL could accelerate acidogenesis, reduce hydrolysis time, and increase the proportion of butyric acid. The findings in this work suggest that PPW is a promising feedstock for butyric acid biosynthesis and appropriate initial OL is beneficial to VFA production.

MPI-VGAE: protein-metabolite enzymatic reaction link learning by variational graph autoencoders.

Enzymatic reactions are crucial to explore the mechanistic function of metabolites and proteins in cellular processes and to understand the etiology of diseases. The increasing number of interconnected metabolic reactions allows the development of in silico deep learning-based methods to discover new enzymatic reaction links between metabolites and proteins to further expand the landscape of existing metabolite-protein interactome. Computational approaches to predict the enzymatic reaction link by metabolite-protein interaction (MPI) prediction are still very limited. In this study, we developed a Variational Graph Autoencoders (VGAE)-based framework to predict MPI in genome-scale heterogeneous enzymatic reaction networks across ten organisms. By incorporating molecular features of metabolites and proteins as well as neighboring information in the MPI networks, our MPI-VGAE predictor achieved the best predictive performance compared to other machine learning methods. Moreover, when applying the MPI-VGAE framework to reconstruct hundreds of metabolic pathways, functional enzymatic reaction networks and a metabolite-metabolite interaction network, our method showed the most robust performance among all scenarios. To the best of our knowledge, this is the first MPI predictor by VGAE for enzymatic reaction link prediction. Furthermore, we implemented the MPI-VGAE framework to reconstruct the disease-specific MPI network based on the disrupted metabolites and proteins in Alzheimer's disease and colorectal cancer, respectively. A substantial number of novel enzymatic reaction links were identified. We further validated and explored the interactions of these enzymatic reactions using molecular docking. These results highlight the potential of the MPI-VGAE framework for the discovery of novel disease-related enzymatic reactions and facilitate the study of the disrupted metabolisms in diseases.

Genome-scale enzymatic reaction prediction by variational graph autoencoders.

Background: Enzymatic reaction networks are crucial to explore the mechanistic function of metabolites and proteins in biological systems and understanding the etiology of diseases and potential target for drug discovery. The increasing number of metabolic reactions allows the development of deep learning-based methods to discover new enzymatic reactions, which will expand the landscape of existing enzymatic reaction networks to investigate the disrupted metabolisms in diseases. Results: In this study, we propose the MPI-VGAE framework to predict metabolite-protein interactions (MPI) in a genome-scale heterogeneous enzymatic reaction network across ten organisms with thousands of enzymatic reactions. We improved the Variational Graph Autoencoders (VGAE) model to incorporate both molecular features of metabolites and proteins as well as neighboring features to achieve the best predictive performance of MPI. The MPI-VGAE framework showed robust performance in the reconstruction of hundreds of metabolic pathways and five functional enzymatic reaction networks. The MPI-VGAE framework was also applied to a homogenous metabolic reaction network and achieved as high performance as other state-of-art methods. Furthermore, the MPI-VGAE framework could be implemented to reconstruct the disease-specific MPI network based on hundreds of disrupted metabolites and proteins in Alzheimer's disease and colorectal cancer, respectively. A substantial number of new potential enzymatic reactions were predicted and validated by molecular docking. These results highlight the potential of the MPI-VGAE framework for the discovery of novel disease-related enzymatic reactions and drug targets in real-world applications. Data availability and implementation: The MPI-VGAE framework and datasets are publicly accessible on GitHub https://github.com/mmetalab/mpi-vgae . Author Biographies: Cheng Wang received his Ph.D. in Chemistry from The Ohio State Univesity, USA. He is currently a Assistant Professor in School of Public Health at Shandong University, China. His research interests include bioinformatics, machine learning-based approach with applications to biomedical networks. Chuang Yuan is a research assistant at Shandong University. He obtained the MS degree in Biology at the University of Science and Technology of China. His research interests include biochemistry & molecular biology, cell biology, biomedicine, bioinformatics, and computational biology. Yahui Wang is a PhD student in Department of Chemistry at Washington University in St. Louis. Her research interests include biochemistry, mass spectrometry-based metabolomics, and cancer metabolism. Ranran Chen is a master graduate student in School of Public Health at University of Shandong, China. Yuying Shi is a master graduate student in School of Public Health at University of Shandong, China. Gary J. Patti is the Michael and Tana Powell Professor at Washington University in St. Louis, where he holds appointments in the Department of Chemisrty and the Department of Medicine. He is also the Senior Director of the Center for Metabolomics and Isotope Tracing at Washington University. His research interests include metabolomics, bioinformatics, high-throughput mass spectrometry, environmental health, cancer, and aging. Leyi Wei received his Ph.D. in Computer Science from Xiamen University, China. He is currently a Professor in School of Software at Shandong University, China. His research interests include machine learning and its applications to bioinformatics. Qingzhen Hou received his Ph.D. in the Centre for Integrative Bioinformatics VU (IBIVU) from Vrije Universiteit Amsterdam, the Netherlands. Since 2020, He has serveved as the head of Bioinformatics Center in National Institute of Health Data Science of China and Assistant Professor in School of Public Health, Shandong University, China. His areas of research are bioinformatics and computational biophysics. Key points: Genome-scale heterogeneous networks of metabolite-protein interaction (MPI) based on thousands of enzymatic reactions across ten organisms were constructed semi-automatically.An enzymatic reaction prediction method called Metabolite-Protein Interaction Variational Graph Autoencoders (MPI-VGAE) was developed and optimized to achieve higher performance compared with existing machine learning methods by using both molecular features of metabolites and proteins.MPI-VGAE is broadly useful for applications involving the reconstruction of metabolic pathways, functional enzymatic reaction networks, and homogenous networks (e.g., metabolic reaction networks).By implementing MPI-VGAE to Alzheimer's disease and colorectal cancer, we obtained several novel disease-related protein-metabolite reactions with biological meanings. Moreover, we further investigated the reasonable binding details of protein-metabolite interactions using molecular docking approaches which provided useful information for disease mechanism and drug design.

Fundamental roles of the Optineurin gene in the molecular pathology of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons (MNs) in the brain and spinal cord. It is caused by multiple factors, including mutations in any one of several specific genes. Optineurin (OPTN) mutation is an essential cause of some familial and sporadic ALS. Besides, as a multifunctional protein, OPTN is highly expressed and conserved in the central nervous system. OPTN exerts its functions by interacting with various proteins, often acting as an adaptor to provide a link between two or more core proteins related to autophagy and inflammation, etc. OPTN mutation mainly results in its function deficiency, which alters these interactions, leading to functional impairment in many processes. Meanwhile, OPTN immunopositive inclusions are also confirmed in the cases of ALS due to C9ORF72, FUS, TARDBP, and SOD1 mutations. Therefore, OPTN gene may play fundamental roles in the molecular pathology of ALS in addition to OPTN mutation. In this review, we summarize the recent advances in the ALS pathology of OPTN defect, such as mitophagy disorder, neuroinflammation, neuronal axonal degeneration, vesicular transport dysfunction, etc., which will provide a reference for research on the pathogenesis and treatment of ALS.

Prediction of protein-protein interaction sites in intrinsically disordered proteins.

Intrinsically disordered proteins (IDPs) participate in many biological processes by interacting with other proteins, including the regulation of transcription, translation, and the cell cycle. With the increasing amount of disorder sequence data available, it is thus crucial to identify the IDP binding sites for functional annotation of these proteins. Over the decades, many computational approaches have been developed to predict protein-protein binding sites of IDP (IDP-PPIS) based on protein sequence information. Moreover, there are new IDP-PPIS predictors developed every year with the rapid development of artificial intelligence. It is thus necessary to provide an up-to-date overview of these methods in this field. In this paper, we collected 30 representative predictors published recently and summarized the databases, features and algorithms. We described the procedure how the features were generated based on public data and used for the prediction of IDP-PPIS, along with the methods to generate the feature representations. All the predictors were divided into three categories: scoring functions, machine learning-based prediction, and consensus approaches. For each category, we described the details of algorithms and their performances. Hopefully, our manuscript will not only provide a full picture of the status quo of IDP binding prediction, but also a guide for selecting different methods. More importantly, it will shed light on the inspirations for future development trends and principles.

Clinical Outcomes After Primary Implantation into Modified One-and-a-Half-Barrel Fibula Free Flap Reconstructed Mandible.

PURPOSE: The aim of this study was to introduce and evaluate a modified one-and-a-half-barrel fibular technique guided by occlusion for functionally reconstructing mandibular defects. MATERIALS AND METHODS: Fifteen patients underwent mandibular reconstruction with the modified one-and-a-half-barrel technique and simultaneous insertion of dental implants. A vascularized fibular segment was used to reconstruct the alveolar ridge of the neomandible with dental implants loaded simultaneously. The inferior border was reconstructed with a nonvascularized segment. Panoramic radiographs were taken 1 week, 6 months, and 12 months after the surgery to measure the vertical height of the fibular segment, calculate the bone resorption rate at different time points, and observe the implant marginal bone loss and crown-to-implant ratio. The OHIP-14 questionnaire was employed to evaluate the perceived outcomes of oral rehabilitation. RESULTS: The vertical height of the vascularized and nonvascularized fibular segments 1 week, 6 months, and 12 months after the surgery was 14.51 ± 1.93, 14.19 ± 1.88, and 13.81 ± 1.78 mm; and 8.65 ± 0.98, 7.72 ± 0.94, and 7.25 ± 0.93 mm, respectively. The bone resorption rate of vascularized and nonvascularized fibular segments was 2.20% ± 1.04% and 10.69% ± 5.73%, respectively, in the first 6 months, and 2.67% ± 1.44% and 6.16% ± 2.75%, respectively, in the latter 6 months, showing a significantly higher resorption rate in the nonvascularized segment (P < .05). The implant marginal bone loss after functional loading was significantly greater than that before dental rehabilitation (P = .001). The OHIP-14 total scores were 20.07 ± 10.24, 19.00 ± 7.82, and 3.93 ± 1.87 before surgery, at 6 months, and at 12 months after surgery, respectively (P = .000). CONCLUSION: The proposed technique not only guarantees the esthetic appearance of patients but also achieves a suitable vertical height to facilitate the placement of the implant at the same time.

DNMT1-Mediated DNA Methylation Targets CDKN2B to Promote the Repair of Retinal Ganglion Cells in Streptozotocin-Induced Mongolian Gerbils during Diabetic Retinopathy.

Objective: DNA methylation played a vital role in the progression of diabetic retinopathy. In this study, we aimed to explore the role of DNA cytosine-5-methyltransferase 1 (DNMT1) in the development of early diabetic retinopathy and its potential underlying mechanism. Methods: Eight-week-old healthy Mongolian gerbils were used to establish type 1 diabetes using streptozotocin (STZ). Alteration of weight, fasting blood glucose, density of RGCs (Tuj1-labeled), and H&E-stained retinal cross sections were applied to evaluate the diabetic retinopathy mouse model. The global DNA methylation level of the retina at different time points after STZ injection was measured using the global methylation assay. Western blot was used to detect the protein expression of DNMT1, DNA methyltransferase 3A (DNMT3A), and 3B (DNMT3B). Quantitative reverse transcription-polymerase chain reactions (qRT-PCR) and western blot were used to determine the expression of CDKN2B. Cell proliferation and cell cycle were evaluated by the MTS assay and flow cytometry. Results: STZ injection caused the increased global DNA methylation level, which reached a maximum at 6 weeks after injection. Moreover, STZ injection caused the damage of RGCs. At 6 weeks after STZ injection, the expression levels of DNMT1 and DNMT3B were significantly increased in the STZ group. DNMT1-induced DNA hypermethylation inhibited the expression of CDKN2B (a negative regulator of cell cycle). DNMT1-mediated DNA methylation facilitated RGC proliferation via regulating the expression of CDKN2B. Conclusion: DNMT1-mediated DNA methylation played an important role in STZ-induced diabetic retinopathy via modulating CDKN2B expression.