Modeling Bellman-error with logistic distribution with applications in reinforcement learning.

In modern Reinforcement Learning (RL) approaches, optimizing the Bellman error is a critical element across various algorithms, notably in deep Q-Learning and related methodologies. Traditional approaches predominantly employ the mean-squared Bellman error (MSELoss) as the standard loss function. However, the assumption of Bellman errors following the Gaussian distribution may oversimplify the nuanced characteristics of RL applications. In this work, we revisit the distribution of Bellman error in RL training, demonstrating that it tends to follow the Logistic distribution rather than the commonly assumed Normal distribution. We propose replacing MSELoss with a Logistic maximum likelihood function (LLoss) and rigorously test this hypothesis through extensive numerical experiments across diverse online and offline RL environments. Our findings consistently show that integrating the Logistic correction into the loss functions of various baseline RL methods leads to superior performance compared to their MSE counterparts. Additionally, we employ Kolmogorov-Smirnov tests to substantiate that the Logistic distribution offers a more accurate fit for approximating Bellman errors. This study also offers a novel theoretical contribution by establishing a clear connection between the distribution of Bellman error and the practice of proportional reward scaling, a common technique for performance enhancement in RL. Moreover, we explore the sample-accuracy trade-off involved in approximating the Logistic distribution, leveraging the Bias-Variance decomposition to mitigate excessive computational resources. The theoretical and empirical insights presented in this study lay a significant foundation for future research, potentially advancing methodologies, and understanding in RL, particularly in the distribution-based optimization of Bellman error.

Mn2+-induced structural flexibility enhances the entire catalytic cycle and the cleavage of mismatches in prokaryotic argonaute proteins.

Prokaryotic Argonaute (pAgo) proteins, a class of DNA/RNA-guided programmable endonucleases, have been extensively utilized in nucleic acid-based biosensors. The specific binding and cleavage of nucleic acids by pAgo proteins, which are crucial processes for their applications, are dependent on the presence of Mn2+ bound in the pockets, as verified through X-ray crystallography. However, a comprehensive understanding of how dissociated Mn2+ in the solvent affects the catalytic cycle, and its underlying regulatory role in this structure-function relationship, remains underdetermined. By combining experimental and computational methods, this study reveals that unbound Mn2+ in solution enhances the flexibility of diverse pAgo proteins. This increase in flexibility through decreasing the number of hydrogen bonds, induced by Mn2+, leads to higher affinity for substrates, thus facilitating cleavage. More importantly, Mn2+-induced structural flexibility increases the mismatch tolerance between guide-target pairs by increasing the conformational states, thereby enhancing the cleavage of mismatches. Further simulations indicate that the enhanced flexibility in linkers triggers conformational changes in the PAZ domain for recognizing various lengths of nucleic acids. Additionally, Mn2+-induced dynamic alterations of the protein cause a conformational shift in the N domain and catalytic sites towards their functional form, resulting in a decreased energy penalty for target release and cleavage. These findings demonstrate that the dynamic conformations of pAgo proteins, resulting from the presence of the unbound Mn2+ in solution, significantly promote the catalytic cycle of endonucleases and the tolerance of cleavage to mismatches. This flexibility enhancement mechanism serves as a general strategy employed by Ago proteins from diverse prokaryotes to accomplish their catalytic functions and provide useful information for Ago-based precise molecular diagnostics.

Protein Engineering with Lightweight Graph Denoising Neural Networks.

Protein engineering faces challenges in finding optimal mutants from a massive pool of candidate mutants. In this study, we introduce a deep-learning-based data-efficient fitness prediction tool to steer protein engineering. Our methodology establishes a lightweight graph neural network scheme for protein structures, which efficiently analyzes the microenvironment of amino acids in wild-type proteins and reconstructs the distribution of the amino acid sequences that are more likely to pass natural selection. This distribution serves as a general guidance for scoring proteins toward arbitrary properties on any order of mutations. Our proposed solution undergoes extensive wet-lab experimental validation spanning diverse physicochemical properties of various proteins, including fluorescence intensity, antigen-antibody affinity, thermostability, and DNA cleavage activity. More than 40% of ProtLGN-designed single-site mutants outperform their wild-type counterparts across all studied proteins and targeted properties. More importantly, our model can bypass the negative epistatic effect to combine single mutation sites and form deep mutants with up to seven mutation sites in a single round, whose physicochemical properties are significantly improved. This observation provides compelling evidence of the structure-based model's potential to guide deep mutations in protein engineering. Overall, our approach emerges as a versatile tool for protein engineering, benefiting both the computational and bioengineering communities.

Metal organic framework-derived CuO/Cu2O polyhedron-CdS quantum dots double Z-scheme heterostructure for cathodic photoelectrochemical detection of Hg2+ in food and environment.

This study employed an innovative copper oxide/cuprous oxide (CuO/Cu2O) polyhedron­cadmium sulphide quantum dots (CdS QDs) double Z-scheme heterostructure as a matrix for the cathodic PEC determination of mercury ions (Hg2+). First, the CuO/Cu2O polyhedral composite was prepared by calcining a copper-based metal organic framework (Cu-MOF). Subsequently, the amino-modified CuO/Cu2O was integrated with mercaptopropionic acid (MPA)-capped CdS QDs to form a CuO/Cu2O polyhedron-CdS QDs double Z-scheme heterostructure, producing a strong cathodic photocurrent. Importantly, this heterostructure exhibited a specifically reduced photocurrent for Hg2+ when using CdS QDs as Hg2+-recognition probe. This was attributed to the extreme destruction of the double Z-scheme heterostructure and the in situ formation of the CuO/Cu2O-CdS/HgS heterostructure. Besides, p-type HgS competed with the matrix for electron acceptors, further decreasing the photocurrent. Consequently, Hg2+ was sensitively assayed, with a low detection limit (0.11 pM). The as-prepared PEC sensor was also used to analyse Hg2+ in food and the environment.

Periodontitis was associated with mesial concavity of the maxillary first premolar: a cross-sectional study.

The association between the anatomical features of teeth and the pathogenesis of periodontitis is well-documented. This study aimed to evaluate the influence of the mesial concavity of the maxillary first premolar on periodontal clinical indices and alveolar bone resorption rates. Employing a cross-sectional design, in 226 patients with periodontitis, we used cone beam computed tomography(CBCT) to examine the mesial concavity and alveolar bone resorption of 343 maxillary first premolar. Periodontal clinical indicators recorded by periodontal probing in the mesial of the maxillary first premolar in patients with periodontitis. Our findings indicate that the presence of mesial concavity at the cemento-enamel junction of the maxillary first premolar was not significantly influenced by either tooth position or patient sex (p > 0.05). Nonetheless, the mesial concavity at the cemento-enamel junction of the maxillary first premolar was found to exacerbate alveolar bone resorption and the inflammatory condition (p < 0.05). We infer that the mesial concavity at the cemento-enamel junction of the maxillary first premolar may contribute to localized alveolar bone loss and accelerate the progression of periodontal disease.

Synergistic effect of composition gradient and morphology on the catalytic activity of amorphous FeCoNi-LDH.

The rational design of electrocatalysts with well-designed compositions and structures for the oxygen evolution reaction (OER) is promising and challenging. Herein, we developed a novel strategy - a one-step double-cation etching sedimentation equilibrium strategy - to synthesize amorphous hollow Fe-Co-Ni layered double hydroxide nanocages with an outer surface of vertically interconnected ultrathin nanosheets (Fe-Co-Ni-LDH), which primarily depends on the in situ etching sedimentation equilibrium of the template interface. This unique vertical nanosheet-shell hierarchical nanostructure possesses enhanced charge transfer, increased active sites, and favorable kinetics during electrolysis, resulting in superb electrocatalytic performance for the oxygen evolution reaction (OER). Specifically, the Fe-Co-Ni-LDH nanocages exhibited remarkable OER activity in alkaline electrolytes and achieved a current density of 100 mA cm-2 at a low overpotential of 272 mV with excellent stability. This powerful strategy provides a profound molecular-level insight into the control of the morphology and composition of 2D layered materials.

The impact of maxillary non-impacted third molars on the distal alveolar bone of adjacent teeth using CBCT: a retrospective study.

OBJECTIVE: The purpose of the study was to determine how the maxillary non-impacted third molars impact the distal region of alveolar bone of adjacent second molars. METHOD AND MATERIALS: The periodontal condition of maxillary second molars for which the neighboring third molars were missing (NM3- group) and those with intact non-impacted third molars (NM3+ group) was analyzed in a retrospective study. Using CBCT, the patients were categorized based on the presence or absence of periodontitis, and the alveolar bone resorption parameters in the distal area of the second molars were measured. RESULTS: A total of 135 patients with 200 maxillary second molars were enrolled in this retrospective study. Compared to the NM3- group, the second molars of the NM3+ group exhibited greater odds of increasing alveolar bone resorption in the distal region (health, OR = 3.60; periodontitis, OR = 7.68), regardless of the presence or absence of periodontitis. In healthy patients, factors such as female sex (OR = 1.48) and age above 25 years old (OR = 2.22) were linked to an elevated risk of alveolar bone resorption in the distal region of the second molars. In patients with periodontitis, male sex (OR = 3.63) and age above 45 years old (OR = 3.97) served as risk factors. CONCLUSIONS: Advanced age, sex, and the presence of non-impacted third molars are risk factors associated with alveolar bone resorption in individuals with adjacent second molars. In addition, the detrimental effects of non-impacted third molars in the population with periodontitis may be exacerbated. From a periodontal perspective, this serves as supportive evidence for the proactive removal of non-impacted third molars.

Nanoparticles exhibiting virus-mimic surface topology for enhanced oral delivery.

The oral delivery of nano-drug delivery systems (Nano-DDS) remains a challenge. Taking inspirations from viruses, here we construct core-shell mesoporous silica nanoparticles (NPs, ~80 nm) with virus-like nanospikes (VSN) to simulate viral morphology, and further modified VSN with L-alanine (CVSN) to enable chiral recognition for functional bionics. By comparing with the solid silica NPs, mesoporous silica NPs and VSN, we demonstrate the delivery advantages of CVSN on overcoming intestinal sequential barriers in both animals and human via multiple biological processes. Subsequently, we encapsulate indomethacin (IMC) into the nanopores of NPs to mimic gene package, wherein the payloads are isolated from bio-environments and exist in an amorphous form to increase their stability and solubility, while the chiral nanospikes multi-sited anchor and chiral recognize on the intestinal mucosa to enhance the penetrability and ultimately improve the oral adsorption of IMC. Encouragingly, we also prove the versatility of CVSN as oral Nano-DDS.

Enantioselective Oral Absorption of Molecular Chiral Mesoporous Silica Nanoparticles.

Inspired by the unique pharmacological effects of chiral drugs in the asymmetrical body environments, it is assumed that the chirality of nanocarriers is also a key factor to determine their oral adsorption efficiency, apart from their size, shape, etc. Herein, l/d-tartaric acid modified mesoporous silica nanoparticles (l/d-CMSNs) are fabricated via a one-pot cocondensation method, and focused on whether the oral adsorption of nanocarriers will be benefited from their chirality. It is found that l-CMSN performed better in the sequential oral absorption processes, including mucus permeation, mucosa bio-adhesion, cellular uptake, intestinal transport and gastrointestinal tract (GIT) retention, than those of the d-chiral (d-CMSN), racemic (dl-CMSN), and achiral (MSN) counterparts. The multiple chiral recognition mechanisms are experimentally and theoretically demonstrated following simple differential adsorption on biointerfaces, wherein electrostatic interaction is the dominant energy. During the oral delivery task, l-CMSN, which is proven to be stable, nonirritative, biocompatible, and biodegradable, is efficiently absorbed into the blood (1.72-2.05-fold higher than other nanocarriers), and helps the loaded doxorubicin (DOX) to achieve better intestinal transport (2.32-27.03-times higher than other samples), satisfactory bioavailability (449.73%) and stronger antitumor effect (up to 95.43%). These findings validated the dominant role of chirality in determining the biological fate of nanocarriers.

Enhancement of intestinal mucosal immunity and immune response to the foot-and-mouth disease vaccine by oral administration of danggui buxue decoction.

This study investigated the effect of Danggui Buxue decoction (DBD) on the immunity of an O-type foot-and-mouth disease (FMD) vaccine and intestinal mucosal immunity. SPF KM mice were continuously and orally administered DBD for 5 d and then inoculated with an O-type FMD vaccine. The contents of a specific IgG antibody and its isotypes IgG1, IgG2a, IgG2b, and IgG3 in serum and SIgA in duodenal mucosa were determined by ELISA at 1 and 3 W after the 2nd immunization. qRT-PCR was used to detect mRNA expression levels of IL-4, IL-10, IFN-γ, and IL-33 in the spleen, and mRNA expression levels of J-chain, pIgR, BAFF, APRIL, IL-10, IFN-γ and IL-33 in the duodenum. The results showed that compared with the control group, oral administration of DBD significantly increased levels of the anti-FMD virus (FMDV)-specific antibodies IgG, IgG1, and IgG2a in the serum of O-type FMD vaccine-immunized mice 1 W after the 2nd immunization (P < 0.05), upregulated mRNA expression levels of spleen lymphocyte cytokines IL-4 and IL-33 (P < 0.05), promoted the secretion of SIgA in duodenal mucosa (P < 0.05). The mRNA expression levels of J-chain, pIgR, BAFF, APRIL, IL-10, and IL-33 in duodenal tissues were upregulated (P < 0.05). This study indicates that DBD has a good promotion effect on the O-type FMD vaccine and the potential to be an oral immune booster.

Effect of downregulated citrate synthase on oxidative phosphorylation signaling pathway in HEI-OC1 cells.

BACKGROUND: Citrate Synthase (Cs) gene mutation (locus ahL4) has been found to play an important role in progressive hearing loss of A/J mice. HEI-OC1 cells have been widely used as an in vitro system to study cellular and molecular mechanisms related to hearing lose. We previously reported the increased apoptosis and the accumulation of reactive oxygen species in shRNACs-1429 cells, a Cs low-expressed cell model from HEI-OCI. The details of the mechanism of ROS production and apoptosis mediated by the abnormal expression of Cs needed to research furtherly. METHODS: iTRAQ proteomics was utilized to detect the differentially expressed proteins (DEPs) caused by low expression of Cs. The GO and KEGG pathways analysis were performed for annotation of the differentially expressed proteins. Protein-protein interaction network was constructed by STRING online database. Immunoblotting was utilized to confirm the protein levels of the the differentially expressed proteins. RESULTS: The differentially expressed proteins were significantly enriched in various signaling pathways mainly related to mitochondrial dysfunction diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease, et al. Most noteworthy, the oxidative phosphorylation pathway was most significantly suppressed in the shRNACs-1429 cells,, in which a total of 10 differentially expressed proteins were enriched and were all downregulated by the abnormal expression of Cs. The downregulations of Ndufb5, Ndufv1 and Uqcrb were confirmed by immunoblotting. Meanwhile, the ATP levels of shRNACs-1429 cells were also reduced. CONCLUSIONS: These results suggest that low level expression of Cs induces the inhibition of oxidative phosphorylation pathway, which is responsible for the high level production of reactive oxygen species and low level of ATP, leading to the apoptosis of cochlear cells. This study may provide new theories for understanding and therapy of progressive hearing loss.

No Evidence of Benefits of Host Nano-Carbon Materials for Practical Lithium Anode-Free Cells.

Nano-carbon-based materials are widely reported as lithium host materials in lithium metal batteries (LMBs); however, researchers report contradictory claims as to where the lithium plating occurs. Herein, the use of pure hollow core-carbon spheres coated on Cu (PHCCSs@Cu) to study the lithium deposition behavior with respect to this type of structure in lithium anode-free cells is described. It is demonstrated that the lithium showed some initial and limited intercalation into the PHCCSs and then plated on the external carbon walls and the top surface of the carbon coating during the charging process. The unfavorable deposition of lithium inside the PHCCSs is discussed from the viewpoint of lithium-ion transport and lithium nucleation. The application potential of PHCCSs and the data from these LMB studies are also discussed.

Embedding graphs on Grassmann manifold.

Learning efficient graph representation is the key to favorably addressing downstream tasks on graphs, such as node or graph property prediction. Given the non-Euclidean structural property of graphs, preserving the original graph data's similarity relationship in the embedded space needs specific tools and a similarity metric. This paper develops a new graph representation learning scheme, namely Egg, which embeds approximated second-order graph characteristics into a Grassmann manifold. The proposed strategy leverages graph convolutions to learn hidden representations of the corresponding subspace of the graph, which is then mapped to a Grassmann point of a low dimensional manifold through truncated singular value decomposition (SVD). The established graph embedding approximates denoised correlationship of node attributes, as implemented in the form of a symmetric matrix space for Euclidean calculation. The effectiveness of Egg is demonstrated using both clustering and classification tasks at the node level and graph level. It outperforms baseline models on various benchmarks.

Sulfur-Rich (NH4)2Mo3S13 as a Highly Reversible Anode for Sodium/Potassium-Ion Batteries.

Sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs) have attracted much attention owing to the inexpensive Na/K metal and satisfactory performance. Currently, there are still difficulties in research anode materials that can insert/extract Na/K ions quickly and stably. Herein, the sulfur-rich (NH4)2Mo3S13 is proposed as the anode for SIBs/PIBs and is obtained by a hydrothermal method. The sulfur-rich (NH4)2Mo3S13 with a three-dimensional structure shows a high capacity and long lifespans for Na+ (at 10 A g-1 the capacity of 165.2 mAh g-1 after 1100 cycles) and K+ (120.7 mAh g-1 at 1 A g-1 retained after 500 cycles) storage. In addition, the (NH4)2Mo3S13 electrode exhibits excellent electrochemical performance at low temperatures (0 °C). The mechanism of Na+ storage in (NH4)2Mo3S13 can be innovatively revealed through the combined use of electrochemical kinetic analysis and a series of ex situ characterization tests. It is believed that the present work identifies (NH4)2Mo3S13 as a promising anode for the SIBs/PIBs and will be of broad interest in research on engineering sulfur-rich transition metal sulfide and on energy storage devices.

A novel mutation in TRIOBP gene leading to congenital deafness in a Chinese family.

BACKGROUND: The autosomal recessive non-syndromic deafness DFNB28 is characterized by prelingual sensorineural hearing loss. The disease is related with mutations in TRIOBP (Trio- and F-actin-Binding Protein) gene, which has three transcripts referred to as TRIOBP-5, TRIOBP - 4 and TRIOBP-1. Among them, TRIOBP-5/- 4 are expressed in the inner ears and crucial for maintaining the structure and function of the stereocilia. METHODS: The proband is a 26-year-old Chinese female. She and her younger brother have being suffered from severe deafness since birth, whereas her parents, who are cousins, have normal communication ability. Hearing impairment of the two siblings was determined by pure tone audiometry. Whole Exome Sequencing (WES) was performed on the genomic DNA of the proband and Sanger sequencing was conducted on the DNA samples of the four family members. RESULTS: Tests of pure tone hearing thresholds showed a severe to profound symmetric hearing loss for the proband and her younger brother. Moreover, a novel TRIOBP c.1342C > T (p.Arg448*) variant was identified by WES in the DNA sample of the proband and confirmed by Sanger sequencing in DNA of the family members. CONCLUSIONS: The TRIOBP c.1342C > T (p.Arg448*) variant is predicted to disrupt TRIOBP-5 and TRIOBP-4, which may lead to the congenital deafness. The results will broaden the spectrum of pathogenic variants in TRIOBP gene. The characteristics of deafness in the family imply that marriage between close relatives should be avoided.

ALA protects against ERS-mediated apoptosis in a cochlear cell model with low citrate synthase expression.

A/J mouse is a model of age-related hearing loss (AHL). Mutation in the citrate synthase (Cs) gene of the mouse plays an important role in the hearing loss and degeneration of cochlear cells. To investigate the pathogenesis of cochlear cell damage in A/J mice resulted from Cs mutation, we downregulated the expression level of CS in HEI-OC1, a cell line of mouse cochlea, by shRNA. The results showed that low CS expression led to low ability of cell proliferation. Further study revealed an increase level of reactive oxygen species (ROS), activation of ATF6 mediated endoplasmic reticulum stress (ERS) and high expression levels of caspase12 and Bax in the cells. Moreover, the AEBSF, an ATF6 inhibitor, could reduce the expression levels of caspase-12 and Bax by inhibiting the hydrolysis of ATF6 in the cells. Finally, antioxidant alpha-lipoic acid (ALA) reduced the ROS levels and the apoptotic signals in the cell model with low CS expression. We therefore conclude that the ERS mediated apoptosis, which is triggered by ROS, may be involved in the cell degeneration in the cochleae of A/J mice.

Otoprotective Effects of α-lipoic Acid on A/J Mice With Age-related Hearing Loss.

OBJECTIVE: A/J mice are a mouse model of age-related hearing loss (AHL) with progressive degeneration of outer hair cells (OHCs), spiral ganglion neurons (SGNs), and stria vascularis. This study was carried out to observe the otoprotective effects of α-lipoic acid on A/J mice. METHODS: A/J mouse pups at postnatal day 7 were randomly distributed into the untreated group, the dimethyl sulfoxide (DMSO) group, and the α-lipoic acid + DMSO group. α-lipoic acid was given to the mice intraperitoneally at a dosage of 50 µg/g body weight every other day. Time course auditory-evoked brainstem response (ABR) thresholds were tested. OHC loss was counted and the densities of SGNs and the width of stria vascularis were measured at 4 and 8 weeks of age. RESULTS: Measurement of the ABR thresholds revealed that hearing loss in A/J mice was attenuated by α-lipoic acid at age from 3 to 8 weeks. Moreover, preservation effects of OHCs, SGNs, and stria vascularis by α-lipoic acid were observed in the cochleae of A/J mice at 4 and 8 weeks of age. CONCLUSION: Hearing loss in A/J mice can be attenuated by α-lipoic acid. The otoprotective effects of α-lipoic acid on A/J mice may be obtained by preserving OHCs, SGNs, and stria vascularis in the cochleae. The oxidative damage related to gene mutations may be a potential target for AHL prevention and therapy.

Type-II/type-II band alignment to boost spatial charge separation: a case study of g-C3N4 quantum dots/a-TiO2/r-TiO2 for highly efficient photocatalytic hydrogen and oxygen evolution.

Efficient spatial charge separation and transfer that are critical factors for solar energy conversion primarily depend on the energetic alignment of the band edges at interfaces in heterojunctions. Herein, we first report that constructing a 0D/0D type-II(T-II)/T-II heterojunction is an effective strategy to ingeniously achieve long-range charge separation by taking a ternary heterojunction of TiO2 and graphitic carbon nitride (g-C3N4) as a proof-of-concept. Incorporating g-C3N4 quantum dots (QCN), as the third component, into the commercial P25 composed of anatase (a-TiO2) and rutile (r-TiO2) can be realized via simply mixing the commercially available Degussa P25 and QCN solution followed by heat treatment. The strong coupling and matching band structures among a-TiO2, r-TiO2 and QCN result in the construction of novel T-II/T-II heterojunctions, which would promote the spatial separation and transfer of photogenerated electrons and holes. Moreover, QCN plays a key role in reinforcing light absorption. Particularly, the unique 0D/0D architecture possesses the advantages of abundant active sites for the photocatalytic reaction. As a result, the optimized QCN/a-TiO2/r-TiO2 heterojunctions exhibit enhanced photocatalytic H2 and O2 evolution, especially the hydrogen evolution rate (49.3 µmol h-1) is 11.7 times that of bare P25 under visible light irradiation, and sufficient catalytic stability as evidenced by the recycling experiments. The remarkably enhanced photocatalytic activity can be attributed to the synergistic effects of the energy level alignment at interfaces, the dimensionality and component of the heterojunctions. This work provides a stepping stone towards the design of novel heterojunctions for photocatalytic water splitting.

Functional characterization of acyl-CoA binding protein in Neospora caninum.

BACKGROUND: Lipid metabolism is pivotal for the growth of apicomplexan parasites. Lipid synthesis requires bulk carbon skeleton acyl-CoAs, the transport of which depends on the acyl-CoA binding protein (ACBP). In Neospora caninum, the causative agent of neosporosis, the FASII pathway is required for growth and pathogenicity. However, little is known about the fatty acid transport mechanism in N. caninum. METHODS: We have identified a cytosolic acyl-CoA binding protein, with highly conserved amino acid residues and a typical acyl-CoA binding domain in N. caninum. The recombinant NcACBP protein was expressed to verify the binding activities of NcACBP in vitro, and the heterologous expression of NcACBP in Δacbp yeast in vivo. Lipid extraction from ΔNcACBP or the wild-type of N. caninum was analyzed by GC-MS or TLC. Furthermore, transcriptome analysis was performed to compare the gene expression in different strains. RESULTS: The NcACBP recombinant protein was able to specifically bind acyl-CoA esters in vitro. A yeast complementation assay showed that heterologous expression of NcACBP rescued the phenotypic defects in Δacbp yeast, indicating of the binding activity of NcACBP in vivo. The disruption of NcACBP did not perturb the parasite's growth but enhanced its pathogenicity in mice. The lipidomic analysis showed that disruption of NcACBP caused no obvious changes in the overall abundance and turnover of fatty acids while knockout resulted in the accumulation of triacylglycerol. Transcriptional analysis of ACBP-deficient parasites revealed differentially expressed genes involved in a wide range of biological processes such as lipid metabolism, posttranslational modification, and membrane biogenesis. CONCLUSIONS: Our study demonstrated that genetic ablation of NcACBP did not impair the survival and growth phenotype of N. caninum but enhanced its pathogenicity in mice. This deletion did not affect the overall fatty acid composition but modified the abundance of TAG. The loss of NcACBP resulted in global changes in the expression of multiple genes. This study provides a foundation for elucidating the molecular mechanism of lipid metabolism in N. caninum.

Interfacial charge modulation: carbon quantum dot implanted carbon nitride double-deck nanoframes for robust visible-light photocatalytic tetracycline degradation.

Steering charge kinetics at the interface is essential to improve the photocatalytic performance of two-dimensional (2D) material-based heterostructures. Herein, we developed a novel strategy-simultaneously building two kinds of heterojunctions- to modulate interfacial charge kinetics in polymeric carbon nitride (CN) for improving the photocatalytic activity. Using a simple one-step thermal condensation of carbon quantum dot (CQD)-contained supramolecular precursors formed in water, the controllable CQD embedded CN nanoframes possessed two kinds of heterogeneous interfaces within seamlessly stitched micro-area two-dimensional in-plane and out-of-plane domains. These two kinds of heterojunctions can effectively enhance its intrinsic driving force to accelerate the separation and transfer of charge along different directions. Furthermore, the hollow double-deck porous CN-CQD nanoframes with a high surface area (296.74 m2 g-1) endowed more exposed active sites. The remarkable visible-light photocatalytic activity of hollow porous CN-CQD nanoframes was demonstrated by degrading tetracycline (TC) and rhodamine (RhB) as the models, whose robust degradation rate constant is approximately 11 and 29 times higher than that of pristine CN, respectively. This work provides a novel strategy for the interfacial design of the heterophase junction with atomic precision.