Systems Genetics Analyses Reveals Key Genes Related to Behavioral Traits in the Striatum of CFW Mice.

The striatum plays a central role in directing many complex behaviors ranging from motor control to action choice and reward learning. In our study, we used 55 male CFW mice with rapid decay linkage disequilibrium to systematically mine the striatum-related behavioral functional genes by analyzing their striatal transcriptomes and 79 measured behavioral phenotypic data. By constructing a gene coexpression network, we clustered the genes into 13 modules, with most of them being positively correlated with motor traits. Based on functional annotations as well as Fisher's exact and hypergeometric distribution tests, brown and magenta modules were identified as core modules. They were significantly enriched for striatal-related functional genes. Subsequent Mendelian randomization analysis verified the causal relationship between the core modules and dyskinesia. Through the intramodular gene connectivity analysis, Adcy5 and Kcnma1 were identified as brown and magenta module hub genes, respectively. Knock outs of both Adcy5 and Kcnma1 lead to motor dysfunction in mice, and KCNMA1 acts as a risk gene for schizophrenia and smoking addiction in humans. We also evaluated the cellular composition of each module and identified oligodendrocytes in the striatum to have a positive role in motor regulation.

The highest-elevation frog provides insights into mechanisms and evolution of defenses against high UV radiation.

Defense against ultraviolet (UV) radiation exposure is essential for survival, especially in high-elevation species. Although some specific genes involved in UV response have been reported, the full view of UV defense mechanisms remains largely unexplored. Herein, we used integrated approaches to analyze UV responses in the highest-elevation frog, Nanorana parkeri. We show less damage and more efficient antioxidant activity in skin of this frog than those of its lower-elevation relatives after UV exposure. We also reveal genes related to UV defense and a corresponding temporal expression pattern in N. parkeri. Genomic and metabolomic analysis along with large-scale transcriptomic profiling revealed a time-dependent coordinated defense mechanism in N. parkeri. We also identified several microRNAs that play important regulatory roles, especially in decreasing the expression levels of cell cycle genes. Moreover, multiple defense genes (i.e., TYR for melanogenesis) exhibit positive selection with function-enhancing substitutions. Thus, both expression shifts and gene mutations contribute to UV adaptation in N. parkeri. Our work demonstrates a genetic framework for evolution of UV defense in a natural environment.

A novel role for KIFC1-MYH9 interaction in triple-negative breast cancer aggressiveness and racial disparity.

African American (AA) women are twice as likely to develop triple-negative breast cancer (TNBC) as women of European descent. Additionally, AA women with TNBC present a much more aggressive disease course than their European American (EA) counterparts. Thus, there is an unmet clinical need to identify race-specific biomarkers and improve survival outcomes in AA patients with TNBC. The minus-end directed microtubule motor protein kinesin family member C1 (KIFC1) promotes centrosome clustering and chromosomal instability and is often overexpressed in TNBC. Previous findings suggest that KIFC1 plays a role in cell proliferation and migration in TNBC cells from AAs and that the levels of nuclear KIFC1 (nKIFC1) are particularly high in AA patients with TNBC. The nuclear localization of KIFC1 in interphase may underlie its previously unrecognized race-specific association. In this study, we found that in TNBC cells derived from AAs, nKIFC1 interacted with the tumor suppressor myosin heavy chain 9 (MYH9) over EA cells. Treatment of AA TNBC cells with commercial inhibitors of KIFC1 and MYH9 disrupted the interaction between KIFC1 and MYH9. To characterize the racial differences in the KIFC1-MYH9-MYC axis in TNBC, we established homozygous KIFC1 knockout (KO) TNBC cell lines. KIFC1 KO significantly inhibited proliferation, migration, and invasion in AA TNBC cells but not in EA TNBC cells. RNA sequencing analysis showed significant downregulation of genes involved in cell migration, invasion, and metastasis upon KIFC1 KO in TNBC cell lines from AAs compared to those from EAs. These data indicate that mechanistically, the role of nKIFC1 in driving TNBC progression and metastasis is stronger in AA patients than in EA patients, and that KIFC1 may be a critical therapeutic target for AA patients with TNBC.

TEAD1, MYO7A and NDUFC2 are novel functional genes associated with glucose metabolism in BXD recombinant inbred population.

AIM: The liver is an important metabolic organ that governs glucolipid metabolism, and its dysfunction may cause non-alcoholic fatty liver disease, type 2 diabetes mellitus, dyslipidaemia, etc. We aimed to systematic investigate the key factors related to hepatic glucose metabolism, which may be beneficial for understanding the underlying pathogenic mechanisms for obesity and diabetes mellitus. MATERIALS AND METHODS: Oral glucose tolerance test (OGTT) phenotypes and liver transcriptomes of BXD mice under chow and high-fat diet conditions were collected from GeneNetwork. QTL mapping was conducted to pinpoint genomic regions associated with glucose homeostasis. Candidate genes were further nominated using a multi-criteria approach and validated to confirm their functional relevance in vitro. RESULTS: Our results demonstrated that plasma glucose levels in OGTT were significantly affected by both diet and genetic background, with six genetic regulating loci were mapped on chromosomes 1, 4, and 7. Moreover, TEAD1, MYO7A and NDUFC2 were identified as the candidate genes. Functionally, siRNA-mediated TEAD1, MYO7A and NDUFC2 knockdown significantly decreased the glucose uptake and inhibited the transcription of genes related to insulin and glucose metabolism pathways. CONCLUSIONS: Our study contributes novel insights to the understanding of hepatic glucose metabolism, demonstrating the impact of TEAD1, MYO7A and NDUFC2 on mitochondrial function in the liver and their regulatory role in maintaining in glucose homeostasis.

The Combination of Quantitative Proteomics and Systems Genetics Analysis Reveals that PTN Is Associated with Sleep-Loss-Induced Cognitive Impairment.

Sleep loss is associated with cognitive dysfunction. However, the detailed mechanisms remain unclear. In this study, we established a para-chlorophenylalanine (PCPA)-induced insomniac mouse model with impaired cognitive function. Mass-spectrometry-based proteomics showed that the expression of 164 proteins was significantly altered in the hippocampus of the PCPA mice. To identify critical regulators among the potential markers, a transcriptome-wide association screening was performed in the BXD mice panel. Among the candidates, the expression of pleiotrophin (Ptn) was significantly associated with cognitive functions, indicating that Ptn-mediates sleep-loss-induced cognitive impairment. Gene co-expression analysis further revealed the potential mechanism by which Ptn mediates insomnia-induced cognitive impairment via the MAPK signaling pathway; that is, the decreased secretion of Ptn induced by insomnia leads to reduced binding to Ptprz1 on the postsynaptic membrane with the activation of the MAPK pathway via Fos and Nr4a1, further leading to the apoptosis of neurons. In addition, Ptn is genetically trans-regulated in the mouse hippocampus and implicated in neurodegenerative diseases in human genome-wide association studies. Our study provides a novel biomarker for insomnia-induced cognitive impairment and a new strategy for seeking neurological biomarkers by the integration of proteomics and systems genetics.

HOXD8 suppresses renal cell carcinoma growth by upregulating SHMT1 expression.

Amplification of amino acids synthesis is reported to promote tumorigenesis. The serine/glycine biosynthesis pathway is a reversible conversion of serine and glycine catalyzed by cytoplasmic serine hydroxymethyltransferase (SHMT)1 and mitochondrial SHMT2; however, the role of SHTM1 in renal cell carcinoma (RCC) is still unclear. We found that low SHMT1 expression is correlated with poor survival of RCC patients. The in vitro study showed that overexpression of SHMT1 suppressed RCC proliferation and migration. In the mouse tumor model, SHMT1 significantly retarded RCC tumor growth. Furthermore, by gene network analysis, we found several SHMT1-related genes, among which homeobox D8 (HOXD8) was identified as the SHMT1 regulator. Knockdown of HOXD8 decreased SHMT1 expression, resulting in faster RCC growth, and rescued the SHMT1 overexpression-induced cell migration defects. Additionally, ChIP assay found the binding site of HOXD8 to SHMT1 promoter was at the -456~-254 bp region. Taken together, SHMT1 functions as a tumor suppressor in RCC. The transcription factor HOXD8 can promote SHMT1 expression and suppress RCC cell proliferation and migration, which provides new mechanisms of SHMT1 in RCC tumor growth and might be used as a potential therapeutic target candidate for clinical treatment.

Inhibition of CPAP-tubulin interaction prevents proliferation of centrosome-amplified cancer cells.

Centrosome amplification is a hallmark of human cancers that can trigger cancer cell invasion. To survive, cancer cells cluster amplified extra centrosomes and achieve pseudobipolar division. Here, we set out to prevent clustering of extra centrosomes. Tubulin, by interacting with the centrosomal protein CPAP, negatively regulates CPAP-dependent peri-centriolar material recruitment, and concurrently microtubule nucleation. Screening for compounds that perturb CPAP-tubulin interaction led to the identification of CCB02, which selectively binds at the CPAP binding site of tubulin. Genetic and chemical perturbation of CPAP-tubulin interaction activates extra centrosomes to nucleate enhanced numbers of microtubules prior to mitosis. This causes cells to undergo centrosome de-clustering, prolonged multipolar mitosis, and cell death. 3D-organotypic invasion assays reveal that CCB02 has broad anti-invasive activity in various cancer models, including tyrosine kinase inhibitor (TKI)-resistant EGFR-mutant non-small-cell lung cancers. Thus, we have identified a vulnerability of cancer cells to activation of extra centrosomes, which may serve as a global approach to target various tumors, including drug-resistant cancers exhibiting high incidence of centrosome amplification.

Semi-Supervised Deep Learning-Based Multi-component Spectral Calibration Modeling for UV-vis and Near-Infrared Spectroscopy without Information Loss.

Spectral analysis is an important method for characterizing and identifying chemical species. However, quantitative spectral analysis of multiple chemical properties in the real world has always been a challenging problem due to the strong correlation, massive noise, and serious information overlapping of the spectral features. Here, we present a new semi-supervised spectral calibration method based on information lossless decoupling of spectral features named NICEM. To realize the separation and extraction of key latent features, the method uses the flow-based model non-linear independent component estimation (NICE) to learn the sample distribution. The spectral data information is transformed into independent latent variables obeying Gaussian distribution by the reversible structure of deep network without information loss, so as to find the essential properties and realize the feature nonlinear decomposition. Moreover, the association between the input latent feature variables and attributes is evaluated by the maximum mutual information coefficient to eliminate the adverse effects of irrelevant information in the latent variable space and mine key information. Since the latent variables are independent in each dimension, the NICEM method is easier to establish an accurate semi-supervised multi-component calibration model even for high overlapping and complex spectral data. The applicability of the proposed spectral modeling method is demonstrated by using three ultraviolet-visible and near-infrared spectral data sets with 15 physical and chemical properties including diesel fuels, corn, and multi-metal ions solution. Results show that the proposed NICEM method has the highest determination coefficient (R2) and significantly improves extrapolation compared with the seven state-of-the-art methods. The proposed method is intuitive because it obviates complex feature engineering and prior knowledge and is a promising spectral calibration tool for quantitative analysis in other spectroscopy applications.

Rapid automatic nucleic acid purification system based on gas-liquid immiscible phase.

The continuous expansion of nucleic acid detection applications has resulted in constant developments in rapid, low-consumption, and highly automated nucleic acid extraction methods. Nucleic acid extraction using magnetic beads across an immiscible phase interface offers significant simplification and parallelization potential. The gas-liquid immiscible phase valve eliminates the requirement for complicated cassettes and is suitable for automation applications. By analyzing the process of magnetic beads crossing the gas-liquid interface, we utilized a low magnetic field strength to drive large magnetic bead packages to cross the gas-liquid interface, providing a solution of high magnetic bead recovery rate for solid-phase extraction with a low-surfactant system based on gas-liquid immiscible phase valve. The recovery rate of magnetic beads was further improved to 90%-95% and the carryover of the reagents was below 1%. Consequently, a chip and an automatic system were developed to verify the applicability of this method for nucleic acid extraction. The Hepatitis B virus serum standard was used for the extraction test. The extraction of four samples was performed within 7 minutes, with nucleic acid recovery maintained above 80% and good purity. Thus, through analysis and experiments, a fast, highly automated, and low-consumption nucleic acid recovery method was proposed in this study.

A robust sparse identification method for nonlinear dynamic systems affected by non-stationary noise.

In the field of science and engineering, identifying the nonlinear dynamics of systems from data is a significant yet challenging task. In practice, the collected data are often contaminated by noise, which often severely reduce the accuracy of the identification results. To address the issue of inaccurate identification induced by non-stationary noise in data, this paper proposes a method called weighted ℓ1-regularized and insensitive loss function-based sparse identification of dynamics. Specifically, the robust identification problem is formulated using a sparse identification mathematical model that takes into account the presence of non-stationary noise in a quantitative manner. Then, a novel weighted ℓ1-regularized and insensitive loss function is proposed to account for the nature of non-stationary noise. Compared to traditional loss functions like least squares and least absolute deviation, the proposed method can mitigate the adverse effects of non-stationary noise and better promote the sparsity of results, thereby enhancing the accuracy of identification. Third, to overcome the non-smooth nature of the objective function induced by the inclusion of loss and regularization terms, a smooth approximation of the non-smooth objective function is presented, and the alternating direction multiplier method is utilized to develop an efficient optimization algorithm. Finally, the robustness of the proposed method is verified by extensive experiments under different types of nonlinear dynamical systems. Compared to some state-of-the-art methods, the proposed method achieves better identification accuracy.

Winter Water Quality Modeling in Xiong'an New Area Supported by Hyperspectral Observation.

Xiong'an New Area is defined as the future city of China, and the regulation of water resources is an important part of the scientific development of the city. Baiyang Lake, the main supplying water for the city, is selected as the study area, and the water quality extraction of four typical river sections is taken as the research objective. The GaiaSky-mini2-VN hyperspectral imaging system was executed on the UAV to obtain the river hyperspectral data for four winter periods. Synchronously, water samples of COD, PI, AN, TP, and TN were collected on the ground, and the in situ data under the same coordinate were obtained. A total of 2 algorithms of band difference and band ratio are established, and the relatively optimal model is obtained based on 18 spectral transformations. The conclusion of the strength of water quality parameters' content along the four regions is obtained. This study revealed four types of river self-purification, namely, uniform type, enhanced type, jitter type, and weakened type, which provided the scientific basis for water source traceability evaluation, water pollution source area analysis, and water environment comprehensive treatment.

Reconstructed magnetic resonance image-based effusion volume assessment for temporomandibular joint arthralgia.

BACKGROUND: Joint effusion is often noticed in magnetic resonance image (MRI) and its diagnostic value for arthralgia of the temporomandibular joint (TMJ) remains obscure. OBJECTIVE: To develop a method for quantitatively evaluating the joint effusion revealed in MRI and its diagnostic value for arthralgia of the TMJ. METHODS: Two-hundreds and twenty-eight TMJs, 101 with arthralgia (Group P) and 105 without (Group NP) from 103 patients, and 22 TMJs (Group CON) from 11 asymptomatic volunteers were examined by using MRI. The effusion volume was measured after constructing a three-dimensional structure of the joint effusion revealed in MRI by using the ITK-SNAP software. The diagnostic capabilities of the effusion volume on arthralgia were evaluated with receiver operating characteristic (ROC) curve analysis. RESULTS: Totally 146 joints showed MRI signs of joint effusion, including nine joints from Group CON. However, the medium volume was greater in Group P (66.65 mm3 ), but was much similar in Group CON (18.33 mm3 ) to Group NP (27.12 mm3 ). The effusion volume larger than 38.20 mm3 was validated to discriminate Group P from Group NP. The AUC value was 0.801 (95% CI 0.728 to 0.874), with a sensitivity of 75% and specificity of 78.9%. The median volume of the joint effusion was larger in those with than without bone marrow oedema, osteoarthritis, Type-III disc configurations, disc displacement and higher signal intensity of the retrodiscal tissue (all, p < .05). CONCLUSION: The present method for evaluate joint effusion volume well discriminated painful TMJs from non-pain ones.

Silencing DTX3L Inhibits the Progression of Cervical Carcinoma by Regulating PI3K/AKT/mTOR Signaling Pathway.

Cervical carcinoma (CC) is the second most prevalent gynecologic cancer in females across the world. To obtain a better understanding of the mechanisms underlying the development of CC, high-resolution label-free mass spectrometry was performed on CC and adjacent normal tissues from eight patients. A total of 2631 proteins were identified, and 46 significant differently expressed proteins (DEPs) were found between CC and normal tissues (p < 0.01, fold change >10 or <0.1). Ingenuity pathway analysis revealed that the majority of the proteins were involved in the regulation of eIF4 and p70S6K signaling and mTOR signaling. Among 46 DEPs, Integrinß6 (ITGB6), PPP1CB, TMPO, PTGES3 (P23) and DTX3L were significantly upregulated, while Desmin (DES) was significantly downregulated in CC tissues compared with the adjacent normal tissues. In in vivo and in vitro experiments, DTX3L knockdown suppressed CC cell proliferation, migration, invasion and xenograft tumorigenesis, and enhanced cell apoptosis. Combination of silencing DTX3L and cisplatin treatment induced higher apoptosis percentage compared to cisplatin treatment alone. Moreover, DTX3L silencing inhibited the PI3K/AKT/mTOR signal pathway. Thus, our results suggested DTX3L could regulate CC progression through the PI3K/AKT/mTOR signal pathway and is potentially a novel biomarker and therapeutic target for CC.

Modulation of Ligand-Gated Glycine Receptors Via Functional Monoclonal Antibodies.

Ion channels are targets of considerable therapeutic interest to address a wide variety of neurologic indications, including pain perception. Current pharmacological strategies have focused mostly on small molecule approaches that can be limited by selectivity requirements within members of a channel family or superfamily. Therapeutic antibodies have been proposed, designed, and characterized to alleviate this selectivity limitation; however, there are no Food and Drug Administration-approved therapeutic antibody-based drugs targeting ion channels on the market to date. Here, in an effort to identify novel classes of engineered ion channel modulators for potential neurologic therapeutic applications, we report the generation and characterization of six (EC50 < 25nM) Cys-loop receptor family monoclonal antibodies with modulatory function against rat and human glycine receptor alpha 1 (GlyRα1) and/or GlyRα3. These antibodies have activating (i.e., positive modulator) or inhibiting (i.e., negative modulator) profiles. Moreover, GlyRα3 selectivity was successfully achieved for two of the three positive modulators identified. When dosed intravenously, the antibodies achieved sufficient brain exposure to cover their calculated in vitro EC50 values. When compared head-to-head at identical exposures, the GlyRα3-selective antibody showed a more desirable safety profile over the nonselective antibody, thus demonstrating, for the first time, an advantage for GlyRα3-selectivity. Our data show that ligand-gated ion channels of the glycine receptor family within the central nervous system can be functionally modulated by engineered biologics in a dose-dependent manner and that, despite high protein homology between the alpha subunits, selectivity can be achieved within this receptor family, resulting in future therapeutic candidates with more desirable drug safety profiles. SIGNIFICANCE STATEMENT: This study presents immunization and multiplatform screening approaches to generate a diverse library of functional antibodies (agonist, potentiator, or inhibitory) raised against human glycine receptors (GlyRs). This study also demonstrates the feasibility of acquiring alpha subunit selectivity, a desirable therapeutic profile. When tested in vivo, these tool molecules demonstrated an increased safety profile in favor of GlyRα3-selectivity. These are the first reported functional GlyR antibodies that may open new avenues to treating central nervous system diseases with subunit selective biologics.

GAD1 alleviates injury-induced optic neurodegeneration by inhibiting retinal ganglion cell apoptosis.

The degeneration of the optic nerve narrows the visual field, eventually causing overall vision loss. This study aimed to identify global protein changes in the retina of optic nerve crushing (ONC) mice and to identify key regulators and pathways involved in injury-induced cell death during the progression of optic neurodegeneration. Label-free quantitative proteomics combined with bioinformatic analysis was performed on retinal protein extracts from ONC and sham-operated mice. Among the 1433 proteins detected, 121 proteins were differentially expressed in the retina of ONC mice. Further bioinformatic analysis showed that various metabolic pathways, including glutamate metabolism and γ-aminobutyric acid (GABA) synthesis, were significantly dysregulated in the injured mouse retinas. Glutamate decarboxylase 1 (GAD1) is the enzyme that converts glutamate into GABA, which was significantly up-regulated during ONC injury. Exogenous GAD1 treatment increased retinal ganglion cell (RGC) survival in the ONC-injured retina. In addition, changes in GAD1 expression were also observed in several other ophthalmic diseases. Vascular endothelial growth factor B (VEGF-B) has previously been reported to protect RGCs from apoptosis and positively regulated the expression of GAD1 in the retina. Notably, combination treatment with GAD1 and VEGF-B also provided strong protection against injury-induced RGC apoptosis. These results suggest that GAD1 expression may serve as an intrinsic protective mechanism that is commonly activated during retinal injury. Targeting GAD1 may serve as a potential strategy to treat optic neurodegenerative diseases.

Co-Catalyzed Reductive Cyclization of Acrylate-Containing 1,6-Enynes.

A Co-catalyzed reductive cyclization of acrylate-containing 1,6-enynes is reported, providing an approach to construct five-membered carbocyclic and heterocyclic scaffolds containing enol ethers and all-carbon quaternary carbons. This novel process enables an E/Z mixture of 1,6-enynes to react with good functional group tolerance and good isolated yields, in an operationally simple manner.

Efficient direct conversion of methane into methanol on CuZn hetero-diatomic catalysts with certain coordination spheres: a DFT study.

The oxidation of methane to a high-value-added chemical, methanol, is a major challenge in catalysis, requiring high energy input to overcome the CH3-H bond activation energy barrier. Based on density functional theory (DFT) calculations, methane oxidation to methanol is catalyzed by hetero-diatomic catalysts (CuZn-NG) with different coordination spheres (CSs). Valence band maximum (VBM), atomic charge and d-band center are selected as analysis methods for the pathway selection and activity of catalysis. The VBM plays a vital role in the catalytic pathway selection, CuZn-NG catalyzes the direct conversion of methane into methanol without side reactions. Alarmingly, the most important reaction step, CH3-H bond activation, is a spontaneously exothermic reaction (releasing 0.06 eV) with CuZn-NPAG as the catalyst, in contrast to most other endothermic reactions in the same activation. By analyzing the atomic charge of the Cu center and O atom, the special electronic phenomenon for this important step is summarized as the "bow-release effect". The CS affects the electronic properties of the active center and further affects the methane oxidation activity. This work provides a useful guide to understand the catalytic selectivity and activity of hetero-diatomic catalysts.

Novel third-generation pyrimidines-based EGFR tyrosine kinase inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer.

The critical T790M secondary mutation in epidermal growth-factor receptor (EGFR) mediates resistance to first- and second-generation EGFR tyrosine kinase inhibitors. Herein, we identified 12 new 2,4-diaryl pyrimidine derivatives containing thiophene fragments as new selective third-generation EGFR inhibitors. Among them, Compound 6a showed good inhibitory activity against EGFR mutant cells with an IC50 value of 0.0022 ± 0.001 µM and was approximately 1730-fold less potent against EGFR WT cells (IC50: 4.499 ± 0.057 µM). Moreover, it strongly affected EGFR-mediated signaling pathways, attenuated tumor proliferation via the intrinsic mitochondrial apoptotic pathway, arrested the cell cycle at G0/G1 phase, and induced apoptosis in H1975 cells. It also displayed appropriate pharmacokinetic (PK) parameters with an oral bioavailability value of 33.57%. Additionally, in vivo studies confirmed that 6a suppressed tumor growth in an H1975 xenograft model (25 mg/kg/d, TGI: 90.24%). Overall, these results suggest that 6a could be a promising lead compound for overcoming the clinical EGFR T790M resistance of patients with non-small-cell lung cancers (NSCLCs).

All-in-one theranostic nano-platform based on polymer nanoparticles for BRET/FRET-initiated bioluminescence imaging and synergistically anti-inflammatory therapy for ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC), a subtype of inflammatory bowel disease (IBD), has evolved into a global burden given its high incidence. There is a clinical need to create better diagnostic and therapeutic approaches to UC. RESULTS: We fabricated P-selectin binding peptide-decorated poly lactic-co-glycolic acid (PBP-PLGA-NP) doped with two lipophilic dyes, DiL and DiD. Meanwhile, two low-toxic anti-inflammatory natural products (betulinic acid [BA] and resveratrol [Res]) were co-loaded in the PBP-PLGA-NP system. The BA/Res-loaded NPs had an average size of around 164.18 nm with a negative zeta potential (- 25.46 mV). Entrapment efficiencies of BA and Res were 74.54% and 52.33%, respectively, and presented a sustained drug release profile. Further, the resulting PBP-PLGA-NP could be internalized by RAW 264.7 cells and Colon-26 cells efficiently in vitro and preferentially localized to the inflamed colon. When intravenously injected with luminol, MPO-dependent bioluminescence imaging to visualize tissue inflammation was activated by the bioluminescence and fluorescence resonance energy transfer (BRET-FRET) effect. Importantly, injected NPs could remarkably alleviate UC symptoms yet maintain intestinal microbiota homeostasis without inducing organ injuries in the mice models of colitis. CONCLUSIONS: This theranostic nano-platform not only serves as a therapeutic system for UC but also as a non-invasive and highly-sensitive approach for accurately visualizing inflammation.

A two-stage reconstruction method for complex networked system with hidden nodes.

Reconstructing the interacting topology from measurable data is fundamental to understanding, controlling, and predicting the collective dynamics of complex networked systems. Many methods have been proposed to address the basic inverse problem and have achieved satisfactory performance. However, a significant challenge arises when we attempt to decode the underlying structure in the presence of inaccessible nodes due to the partial loss of information. For the purpose of improving the accuracy of network reconstruction with hidden nodes, we developed a robust two-stage network reconstruction method for complex networks with hidden nodes from a small amount of observed time series data. Specifically, the proposed method takes full advantage of the natural sparsity of complex networks and the potential symmetry constraints in dynamic interactions. With robust reconstruction, we can not only locate the position of hidden nodes but also precisely recover the overall network structure on the basis of compensated nodal information. Extensive experiments are conducted to validate the effectiveness of the proposed method and superiority compared with ordinary methods. To some extent, this work sheds light on addressing the inverse problem, of which the system lacks complete exploration in the network science community.