Graph-pMHC: graph neural network approach to MHC class II peptide presentation and antibody immunogenicity.

Antigen presentation on MHC class II (pMHCII presentation) plays an essential role in the adaptive immune response to extracellular pathogens and cancerous cells. But it can also reduce the efficacy of large-molecule drugs by triggering an anti-drug response. Significant progress has been made in pMHCII presentation modeling due to the collection of large-scale pMHC mass spectrometry datasets (ligandomes) and advances in machine learning. Here, we develop graph-pMHC, a graph neural network approach to predict pMHCII presentation. We derive adjacency matrices for pMHCII using Alphafold2-multimer and address the peptide-MHC binding groove alignment problem with a simple graph enumeration strategy. We demonstrate that graph-pMHC dramatically outperforms methods with suboptimal inductive biases, such as the multilayer-perceptron-based NetMHCIIpan-4.0 (+20.17% absolute average precision). Finally, we create an antibody drug immunogenicity dataset from clinical trial data and develop a method for measuring anti-antibody immunogenicity risk using pMHCII presentation models. Our model increases receiver operating characteristic curve (ROC)-area under the ROC curve (AUC) by 2.57% compared to just filtering peptides by hits in OASis alone for predicting antibody drug immunogenicity.

The FIB-4 scores in the emergency department to predict the outcomes of COVID-19 patients in taiwan.

Objective: We aimed to determine the reliability of using the Fibrosis-4 (FIB-4) index in COVID-19 patients without underlying liver illness. Method: We employed multivariate logistic regression to identify variables that exhibited statistically significant influence on the ultimate outcome. Multilayer perceptron analysis was employed to develop a prediction model for the FIB-4 index concerning ICU admission and intubation rates. However, the scarcity of cases rendered the assessment of the mortality rate unfeasible. We plotted ROC curves to analyze the predictive strength of the FIB-4 index across various age groups. Result: In univariate logistic regression, only the FIB-4 index and respiratory rate demonstrated statistical significance on all poor outcomes. The FIB-4 index for mortality prediction had an ROC and AUC of 0.863 (95% CI: 0.781-0.9444). It demonstrates predictive power across age groups, particularly for age ≥65 (AUC: 0.812, 95% CI: 0.6571-0.9673) and age <65 (AUC: 0.878, 95% CI: 0.8012-0.9558). Its sensitivity for intubation and ICU admission prediction is suboptimal. Conclusion: FIB-4 index had promising power in prediction of mortality rate in all age groups.

Effects of Building Directions on Microstructure, Impurity Elements and Mechanical Properties of NiTi Alloys Fabricated by Laser Powder Bed Fusion.

For NiTi alloys prepared by the Laser Powder Bed Fusion (LPBF), changes in the building directions will directly change the preferred orientation and thus directly affect the smart properties, such as superelasticity, as well as change the distribution state of defects and impurity elements to affect the phase transformation behaviour, which in turn affects the smart properties at different temperatures. In this study, the relationship between impurity elements, the building directions, and functional properties; the effects of building directions on the crystallographic anisotropy; phase composition; superelastic properties; microhardness; geometrically necessary dislocation (GND) density; and impurity element content of NiTi SMAs fabricated by LPBF were systematically studied. Three building directions measured from the substrate, namely, 0°, 45° and 90°, were selected, and three sets of cylindrical samples were fabricated with the same process parameters. Along the building direction, a strong <100>//vertical direction (VD) texture was formed for all the samples. Because of the difference in transformation temperature, when tested at 15 °C, the sample with the 45° orientation possessed the highest strain recovery of 3.2%. When tested at the austenite phase transformation finish temperature (Af)+10 °C, the 90° sample had the highest strain recovery of 5.83% and a strain recovery rate of 83.3%. The sample with the 90° orientation presented the highest microhardness, which was attributed to its high dislocation density. Meanwhile, different building directions had an effect on the contents of O, C, and N impurity elements, which affected the transformation temperature by changing the Ni/Ti ratio. This study innovatively studied the impurity element content and GND densities of compressive samples with three building directions, providing theoretical guidance for LPBFed NiTi SMA structural parts.

Degradation performance of methylene blue in metal nanoparticle modified 3D mesoporous wood microchannels.

Wood has a rich three-dimensional pore structure and many bottom-up nanochannels. However, the structure of wood itself has limited ability to adsorb dyes, so the effective combination of the unique structure of wood and Pd NPs was studied to achieve efficient degradation of dyes. First, the three-dimensional structure of natural wood is optimized by combining the complex pore structure of wood with Pd NPs to improve the contact process between the dye and Pd NPs. Then, Pd (II) ion can be well reduced to Pd NPs by wood lignin. In addition, Pd NPs can be fixed by hydroxyl groups on cellulose in wood. The flow state inside Pd NPs/wood film and the contact area between catalyst and dye were discussed in detail by hydrodynamic simulation, which filled the gap. It provides reference for composite structure. When Pd NPs/wood membrane was used to treat methylene blue (MB), the degradation efficiency was up to 96.7%, which was 90% higher than that of natural wood. Its TOF value was 1.82 molMB molPd-1min-1, which was higher than that in the previous literature. Therefore, the novelty of this study is that the mechanism of catalytic degradation of MB by Pd nanoparticles/wood composites is reported for the first time. The internal flow mode and contact condition of the new material are understood, which has a good application prospect.

Genomics comparisons of three chromosome-level mudskipper genome assemblies reveal molecular clues for water-to-land evolution and adaptation.

INTRODUCTION: Mudskippers are a large group of amphibious fishes that have developed many morphological and physiological capacities to live on land. Genomics comparisons of chromosome-level genome assemblies of three representative mudskippers, Boleophthalmus pectinirostris (BP), Periophthalmus magnuspinnatus (PM) and P. modestus (PMO), may be able to provide novel insights into the water-to-land evolution and adaptation. METHODS: Two chromosome-level genome assemblies for BP and PM were respectively sequenced by an integration of PacBio, Nanopore and Hi-C sequencing. A series of standard assembly and annotation pipelines were subsequently performed for both mudskippers. We also re-annotated the PMO genome, downloaded from NCBI, to obtain a redundancy-reduced annotation. Three-way comparative analyses of the three mudskipper genomes in a large scale were carried out to discover detailed genomic differences, such as different gene sizes, and potential chromosomal fission and fusion events. Comparisons of several representative gene families among the three amphibious mudskippers and some other teleosts were also performed to find some molecular clues for terrestrial adaptation. RESULTS: We obtained two high-quality haplotype genome assemblies with 23 and 25 chromosomes for BP and PM respectively. We also found two specific chromosome fission events in PM. Ancestor chromosome analysis has discovered a common fusion event in mudskipper ancestor. This fusion was then retained in all the three mudskipper species. A loss of some SCPP (secretory calcium-binding phosphoprotein) genes were identified in the three mudskipper genomes, which could lead to reduction of scales for a part-time terrestrial residence. The loss of aanat1a gene, encoding an important enzyme (arylalkylamine N-acetyltransferase 1a, AANAT1a) for dopamine metabolism and melatonin biosynthesis, was confirmed in PM but not in PMO (as previously reported existence in BP), suggesting a better air vision of PM than both PMO and BP. Such a tiny variation within the genus Periophthalmus exemplifies to prove a step-by-step evolution for the mudskippers' water-to-land adaptation. CONCLUSION: These high-quality mudskipper genome assemblies will become valuable genetic resources for in-depth discovery of genomic evolution for the terrestrial adaptation of amphibious fishes.

Ag3PO4-anchored La2Ti2O7 nanorod as a Z-Scheme heterostructure composite with boosted photogenerated carrier separation and enhanced photocatalytic performance under natural sunlight.

Developing wide spectra-responsive photocatalysts has attracted considerable attention in the photocatalytic technology to achieve excellent catalytic activity. Ag3PO4, with strong response to light spectra shorter than 530 nm, shows extremely outstanding photocatalytic oxidation ability. Unfortunately, the photocorrosion of Ag3PO4 is still the biggest obstacle to its application. Herein, the La2Ti2O7 nanorod was used to anchor Ag3PO4 nanoparticles in this study, and a novel Z-Scheme La2Ti2O7/Ag3PO4 heterostructure composite was constructed. Remarkably, the composite showed strong responsive to most of the spectra in natural sunlight. The Ag0 formed in-situ acted as the recombination center of photogenerated carriers, which promoted their efficient separation and contributed to the improved photocatalytic performance of the heterostructure. When the mass ratio of Ag3PO4 in the La2Ti2O7/Ag3PO4 catalyst was 50%, the degradation rate constant of Rhodamine B (RhB), methyl orange (MO), chloroquine phosphate (CQ), tetracycline (TC), and phenol under natural sunlight irradiation were 0.5923, 0.4463, 0.1399, 0.0493, and 0.0096 min-1, respectively. Furthermore, the photocorrosion of the composite was greatly inhibited, 76.49% of CQ and 83.96% of RhB were still degraded after four cycles. Besides, the holes and O2•- played a significant role in RhB degradation, and it included multiple mechanisms of deethylation, deamination, decarboxylation, and cleavage of ring-structures. Moreover, the treated solution can also show safety to the water receiving environment. Overall, the synthesized Z-Scheme La2Ti2O7/Ag3PO4 composite exhibited immense potential for removing various organic pollutants through photocatalytic technology under natural sunlight irradiation.

Whole genome sequencing of the fast-swimming Southern bluefin tuna (Thunnus maccoyii).

The economically important Southern bluefin tuna (Thunnus maccoyii) is a world-famous fast-swimming fish, but its genomic information is limited. Here, we performed whole genome sequencing and assembled a draft genome for Southern bluefin tuna, aiming to generate useful genetic data for comparative functional prediction. The final genome assembly is 806.54 Mb, with scaffold and contig N50 values of 3.31 Mb and 67.38 kb, respectively. Genome completeness was evaluated to be 95.8%. The assembled genome contained 23,403 protein-coding genes and 236.1 Mb of repeat sequences (accounting for 29.27% of the entire assembly). Comparative genomics analyses of this fast-swimming tuna revealed that it had more than twice as many hemoglobin genes (18) as other relatively slow-moving fishes (such as seahorse, sunfish, and tongue sole). These hemoglobin genes are mainly localized in two big clusters (termed as "MNË® and "LAË® respectively), which is consistent with other reported fishes. However, Thr39 of beta-hemoglobin in the MN cluster, conserved in other fishes, was mutated as cysteine in tunas including the Southern bluefin tuna. Since hemoglobins are reported to transport oxygen efficiently for aerobic respiration, our genomic data suggest that both high copy numbers of hemoglobin genes and an adjusted function of the beta-hemoglobin may support the fast-swimming activity of tunas. In summary, we produced a primary genome assembly and predicted hemoglobin-related roles for the fast-swimming Southern bluefin tuna.

Microstructure Transformation in Laser Additive Manufactured NiTi Alloy with Quasi-In-Situ Compression.

For NiTi alloys, different additive manufacturing processes may have different compressive recovery capabilities. In particular, there are relatively few studies on the compressive recovery ability of NiTi alloys by the laser-directed energy deposition (LDED) process. In this paper, the compression recovery properties of NiTi alloys with the LDED process were investigated quasi-in-situ by means of transmission electron microscopy, an electron backscatter diffractometer, and focused ion beam-fixed-point sample preparation. The results showed that the material can be completely recovered under 4% deformation and the B19' martensite phase content and dislocation density are basically unchanged. However, the recovery rate was only 90% and the unrecoverable strain was 0.86% at 8% deformation. Meanwhile, the B19' martensite phase content and dislocation density of the material increased. Furthermore, with the increase in deformation, the relative dislocation pinning effect of the Ti2Ni precipitated phase in the alloy was enhanced, which reduced the compressive strain recovery to a certain extent.

The in Vitro Fermentation of Cordyceps militaris Polysaccharides Changed the Simulated Gut Condition and Influenced Gut Bacterial Motility and Translocation.

The motility ability of intestinal lipopolysaccharide (LPS)-producing bacteria determines their translocation to the enterohepatic circulation and works as an infectious complication. In this study, the health effects of Cordyceps militaris polysaccharides (CMPs) were re-evaluated based on whether these polysaccharides could affect the motility of gut commensal LPS-producing bacteria and impede their translocation. The results showed that CMP-m fermentation in the gut could change the chemical environment, leading to a decrease in velocity and a shift in the motility pattern. Further study suggested that detachment/fragmentation of flagella, decreased motor forces, and changed chemical conditions might account for this weakened motility. The adhesion and invasion abilities of gut bacteria were also reduced, with lower expression of virulence-related genes. These results indicated that the health regulation effects of CMP-m might be through decreasing the motility of LPS-producing bacteria, hindering their translocation and therefore reducing the LPS level in the enterohepatic circulation.

Adsorption performance of tetracycline by the biomass ash derived from the pyrolysis of FeCl3-activated municipal sludge without gas protection.

The municipal sludge activated by FeCl3 solution was pyrolyzed at 500 °C without gas protection, and the pyrolysis products, named as biomass ash, could effectively adsorb tetracycline (TC) from aqueous solution. Different FeCl3 concentrations could directly affect the physicochemical properties of the biomass ash, so that the biomass ash as adsorbent showed different adsorption efficiency toward TC. The activation of FeCl3 increased the oxygen-containing functional groups and surface polarities of the biomass ash. When the concentration of FeCl3 solution was 0.5 mol/L, the biomass ash behaved the maximum specific surface area (37.74 m2/g) and the best adsorption efficiency. The pseudo-second-order kinetics model and the Freundlich multi-molecule model could fully explain the TC adsorption process by the biomass ash pyrolyzed from municipal sludge activated by FeCl3. Moreover, the adsorption mechanism was mainly attributed to the chemical adsorption.

Biomass ash pyrolyzed from municipal sludge and its adsorption performance toward tetracycline: effect of pyrolysis temperature and KOH activation.

Large amount of municipal sludge is difficult to handle; its resource utilization is an effective measure. In this study, the municipal sludge from sewage treatment plant was pyrolyzed without gas protection at different temperatures and potassium hydroxide (KOH) concentrations for activation. The pyrolysis products, named biomass ash, with higher surface area and enriched pore structures could be obtained at the pyrolysis temperature of 773 K. Moreover, the KOH activation for raw municipal sludge could further increase the surface area of the pyrolysis biomass ash. The maximum specific surface area was 44.71 m2/g, which was obtained under 2 mol/L KOH activation before pyrolysis at 773 K. And in this situation, the obtained pyrolysis biomass ash as adsorbent showed the maximum adsorption capacity of 50.75 mg/g toward tetracycline (TC). Moreover, the TC adsorption onto pyrolysis biomass ash obtained under various conditions followed the pseudo-second-order kinetic model. Adsorption thermodynamics analysis suggested the TC adsorption onto the pyrolysis biomass ash with no pre-activation was mainly due to the multi-molecule heterogeneous adsorption, while the TC adsorption onto pyrolysis biomass ash pretreated through the activation of KOH followed the monomer adsorption mechanism. This different adsorption mechanism was largely related to the pore structure, polarity, and aromaticity of the adsorbent.

Ag3PO4-based photocatalysts and their application in organic-polluted wastewater treatment.

Semiconductor photocatalysis technology has shown great potential in the field of organic pollutant removal, as it can use clean and pollution-free solar energy as driving force. The discovery of silver phosphate (Ag3PO4) is a major breakthrough in the field of visible light responsive semiconductor photocatalysis due to its robust capacity to absorb visible light < 520 nm. Furthermore, the holes produced in Ag3PO4 under light excitation possess a strong oxidation ability. However, the strong oxidation activity of Ag3PO4 is only achieved in the presence of electron sacrifice agents. Otherwise, photocorrosion would greatly reduce the reuse efficiency of Ag3PO4. This review thus focuses on the structural characteristics and preparation methods of Ag3PO4. Particularly, the recent advances in noble metal deposition, ion doping, and semiconductor coupling, as well as methods of magnetic composite modification for the improvement of catalytic activity and recycling efficiency of Ag3PO4-based catalysts, were also discussed, and all of these measures could enhance the catalytic performance of Ag3PO4 toward organic pollutants degradation. Additionally, some potential modification methods for Ag3PO4 were also proposed. This review thus provides insights into the advantages and disadvantages of the application of Ag3PO4 in the field of photocatalysis, clarifies the photocorrosion essence of Ag3PO4, and reveals the means to improve photocatalytic activity and stability of Ag3PO4. Furthermore, it provides a theoretical and methodological basis for studying Ag3PO4-based photocatalyst and also compiles valuable information regarding the photocatalytic treatment of organic polluted wastewater.

Novel visible-light-driven SrCoO3/Ag3PO4 heterojunction with enhanced photocatalytic performance for tetracycline degradation.

The semiconductor photocatalytic technology has been considerably studied due to its excellent catalytic performance in water pollution control. Herein, in this study, novel SrCoO3/Ag3PO4 composite materials with different SrCoO3 content were synthesized via a simple hydrothermal synthesis method. The characteristics of the as-prepared samples were detected through SEM/HRTEM, XRD, UV-vis DRS, PL, ESR, FT-IR, and XPS techniques, and then, the photocatalytic performance of SrCoO3/Ag3PO4 toward the degradation of tetracycline was investigated. When the mass ratio of SrCoO3 and Ag3PO4 in the composite was 1:1.5, the degradation rate constant of tetracycline in SrCoO3/Ag3PO4 (1:1.5) system is 0.0102 min-1, which is 1.7 times that of the Ag3PO4, and 3.78 times that of the SrCoO3. In addition, reactive species were also analyzed through the free radical trapping experiment and DMPO spin-trapping ESR spectra analysis, showing that OH•, h+, and O2•-participated in the catalytic degradation process of tetracycline to varying degrees. Finally, the photocatalytic mechanism of SrCoO3/Ag3PO4 was also proposed.

A chromosome-level genome assembly of the striped catfish (Pangasianodon hypophthalmus).

Striped catfish (Pangasianodon hypophthalmus), belonging to the Pangasiidae family, has become an economically important fish with wide cultivation in Southeast Asia. Owing to the high-fat trait, it is always considered as an oily fish. In our present study, a high-quality genome assembly of the striped catfish was generated by integration of Illumina short reads, Nanopore long reads and Hi-C data. A 731.7-Mb genome assembly was finally obtained, with a contig N50 of 3.5 Mb, a scaffold N50 of 29.5 Mb, and anchoring of 98.46% of the assembly onto 30 pseudochromosomes. The genome contained 36.9% repeat sequences, and a total 18,895 protein-coding genes were predicted. Interestingly, we identified a tandem triplication of fatty acid binding protein 1 gene (fabp1; thereby named as fabp1-1, fabp1-2 and fabp1-3 respectively), which may be related to the high fat content in striped catfish. Meanwhile, the FABP1-2 and -3 isoforms differed from FABP1-1 by several missense mutations including R126T, which may affect the fatty acid binding properties. In summary, we report a high-quality chromosome-level genome assembly of the striped catfish, which provides a valuable genetic resource for biomedical studies on the high-fat trait, and lays a solid foundation for practical aquaculture and molecular breeding of this international teleost species.

The first Conus genome assembly reveals a primary genetic central dogma of conopeptides in C. betulinus.

Although there are various Conus species with publicly available transcriptome and proteome data, no genome assembly has been reported yet. Here, using Chinese tubular cone snail (C. betulinus) as a representative, we sequenced and assembled the first Conus genome with original identification of 133 genome-widely distributed conopeptide genes. After integration of our genomics, transcriptomics, and peptidomics data in the same species, we established a primary genetic central dogma of diverse conopeptides, assuming a rough number ratio of ~1:1:1:10s for the total genes: transcripts: proteins: post-translationally modified peptides. This ratio may be special for this worm-hunting Conus species, due to the high diversity of various Conus genomes and the big number ranges of conopeptide genes, transcripts, and peptides in previous reports of diverse Conus species. Only a fraction (45.9%) of the identified conotopeptide genes from our achieved genome assembly are transcribed with transcriptomic evidence, and few genes individually correspond to multiple transcripts possibly due to intraspecies or mutation-based variances. Variable peptide processing at the proteomic level, generating a big diversity of venom conopeptides with alternative cleavage sites, post-translational modifications, and N-/C-terminal truncations, may explain how the 133 genes and ~123 transcripts can generate thousands of conopeptides in the venom of individual C. betulinus. We also predicted many conopeptides with high stereostructural similarities to the putative analgesic ω-MVIIA, addiction therapy AuIB and insecticide ImI, suggesting that our current genome assembly for C. betulinus is a valuable genetic resource for high-throughput prediction and development of potential pharmaceuticals.

In silico tools for accurate HLA and KIR inference from clinical sequencing data empower immunogenetics on individual-patient and population scales.

Immunogenetic variation in humans is important in research, clinical diagnosis and increasingly a target for therapeutic intervention. Two highly polymorphic loci play critical roles, namely the human leukocyte antigen (HLA) system, which is the human version of the major histocompatibility complex (MHC), and the Killer-cell immunoglobulin-like receptors (KIR) that are relevant for responses of natural killer (NK) and some subsets of T cells. Their accurate classification has typically required the use of dedicated biological specimens and a combination of in vitro and in silico efforts. Increased availability of next generation sequencing data has led to the development of ancillary computational solutions. Here, we report an evaluation of recently published algorithms to computationally infer complex immunogenetic variation in the form of HLA alleles and KIR haplotypes from whole-genome or whole-exome sequencing data. For both HLA allele and KIR gene typing, we identified tools that yielded >97% overall accuracy for four-digit HLA types, and >99% overall accuracy for KIR gene presence, suggesting the readiness of in silico solutions for use in clinical and high-throughput research settings.