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Fibroblast activation protein (FAP), a type II integral membrane serine protease, is a promising target for tumor diagnosis and therapy. OncoFAP has been recently discovered for PET imaging procedures for various solid malignancies. In this study, we presented the development of manual radiolabeling procedures for the preparation of OncoFAP-based radiopharmaceuticals for cancer imaging. A novel series of [68Ga/177Lu]Ga/Lu-FAPI-FUSCC-I/II were produced with high radiochemical yields. [68Ga]Ga-FAPI-FUSCC-I/II and [177Lu]Lu-FAPI-FUSCC-I/II were stable in phosphate-buffered saline, fetal bovine serum, and human serum for at least 3 h. In vitrocellular uptake and blocking experiments implied that they had specificity to FAP. Additionally, the low nanomolar IC50values of FAPI-FUSCC-II indicated that it had a high target affinity to FAP. The in vivobiodistribution and blocking study in mice bearing HT-1080-FAP tumors showed that both exhibited specific tumor uptake. [68Ga]Ga-FAPI-FUSCC-II showed a higher tumor uptake and a higher tumor/nontarget ratio than [68Ga]Ga-FAPI-FUSCC-I and [68Ga]Ga-FAPI-04. The results of ex vivobiodistribution were in accordance with the biodistribution results. Clinical [68Ga]Ga-FAPI-FUSCC-II-PET/CT imaging further demonstrated its favorable biodistribution and kinetics with elevated and reliable uptake by primary tumors (maximum standardized uptake value (SUVmax), 12.17 ± 6.67) and distant metastases (SUVmax, 9.24 ± 4.28). In summary, [68Ga]Ga-FAPI-FUSCC-II displayed increased tumor uptake and retention compared to [68Ga]Ga-FAPI-04, giving it potential as a promising tracer for the diagnostic imaging of malignant tumors with positive FAP expression.

In the field of electromagnetic wave (EMW) absorption, carbon matrix materials based on metal–organic frameworks (MOFs) have drawn more interest as a result of their outstanding advantages, such as porous structure, lightweight, controlled morphology, etc. However, how to broaden the effective absorption bandwidth [EAB; reflection loss (RL) ≤ −10 dB] is still a challenge. In this paper, large microsphere structures of a Co/C composite composed of small particle clusters were successfully prepared by the solvothermal method and annealing treatment. At a filling ratio of 40 wt %, the Co/C composite shows attractive microwave absorption (MA) performance after being annealed at 600 °C in an atmosphere of argon. With an EAB of 6.32 GHz (9.92–16.24 GHz) and a thickness of just 2.57 mm, the minimum RL can be attained at −54.55 dB. Most importantly, the EAB can attain 7.12 GHz (10.88–18.0 GHz) when the thickness is 2.38 mm, which is larger than that of the majority of MOF-derived composites. The superior MA performance is strongly related to excellent impedance matching and a higher attenuation constant. This study provides a simple strategy for synthesizing a MOF-derived Co/C composite with a wide EAB.

ABSTRACTMacroautophagy/autophagy has been utilized by many viruses, including foot-and-mouth disease virus (FMDV), to facilitate replication, while the underlying mechanism of the interplay between autophagy and innate immune responses is still elusive. This study showed that HDAC8 (histone deacetylase 8) inhibits FMDV replication by regulating innate immune signal transduction and antiviral response. To counteract the HDAC8 effect, FMDV utilizes autophagy to promote HDAC8 degradation. Further data showed that FMDV structural protein VP3 promotes autophagy during virus infection and interacts with and degrades HDAC8 in an AKT-MTOR-ATG5-dependent autophagy pathway. Our data demonstrated that FMDV evolved a strategy to counteract host antiviral activity by autophagic degradation of a protein that regulates innate immune response during virus infection.Abbreviations: 3-MA: 3-methyladenine; ATG: autophagy related; Baf-A1: bafilomycin A1; CCL5: C-C motif chemokine ligand 5; Co-IP: co-immunoprecipitation; CQ: chloroquine phosphate; DAPI: 4”,6-diamidino-2-phenylindole; FMDV: foot-and-mouth disease virus; HDAC8: histone deacetylase 8; ISG: IFN-stimulated gene; IRF3: interferon regulatory factor 3; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; MAVS: mitochondria antiviral signaling protein; OAS: 2”−5’-oligoadenylate synthetase; RB1: RB transcriptional corepressor 1; SAHA: suberoylanilide hydroxamic acid; TBK1: TANK binding kinase 1; TCID50: 50% tissue culture infectious doses; TNF/TNF-α: tumor necrosis factor; TSA: trichostatin A; UTR: untranslated region.

Gradient boosting machine (GBM) is a powerful and widely used type of ensemble machine learning methods, among which the most famous one is XGBoost (XGB). However, the cost of running large GBMs on hardware could become prohibitive given stringent resources. Ensemble reduction on boosting ensemble is intrinsically hard because member models are constructed in a sequential order, where the training targets for latter ones depend on the performance of the former ones. In this work, a GBM reduction framework is proposed for the first time to tackle the problem. For the first time, the framework supports automatic hardware implementation of regression tree ensembles. Experiments on 24 datasets from various applications demonstrate that our method reduces overall area utilization by 81.60% (80.64%) and power consumption by 21.15% (19.06%), while exceeding or successfully maintaining the performance level comparing with the original XGB (LightGBM) ensembles. In comparative experiments, to attain approximately the same accuracy level as our framework or XGB, deep learning-based solutions require > $52.7\times $ footprints, $6.0\times $ power consumption, and $1.4\times $ training time. Equipped with tunable parameters, the framework is expected to seek a Pareto optimal front considering hardware resource limitation, accuracy and stability, and computation (training) efficiency.

Isolation of antigen-specific plasma B cells had been challenging until the recent arrival of the Beacon platform. Leveraging light-sorting technology, Beacon can perform high-throughput screening of plasma B cells on a chip to sort single cells with the desired antigen specificity. Here, we present a protocol for isolating antigen-specific plasma B cells from immunized mice using Beacon, sequencing the encoded B cell receptors (BCRs), and cloning and expressing the resulting antibodies. This protocol can easily be extended to human samples.

To model the atmospheric dispersion of radionuclides released from nuclear accident is very important for nuclear emergency. But the uncertainty of model parameters, such as source term and meteorological data, may significantly affect the prediction accuracy. Data assimilation (DA) is usually used to improve the model prediction with the measurements. The paper proposed a parameter bias transformation method combined with Lagrangian puff model to perform DA. The method uses the transformation of coordinates to approximate the effect of parameters bias. The uncertainty of four model parameters is considered in the paper: release rate, wind speed, wind direction and plume height. And particle swarm optimization is used for searching the optimal parameters. Twin experiment and Kincaid experiment are used to evaluate the performance of the proposed method. The results show that the proposed method can effectively increase the reliability of model prediction and estimate the parameters. It has the advantage of clear concept and simple calculation. It will be useful for improving the result of atmospheric dispersion model at the early stage of nuclear emergency.

ABSTRACTThis study devised an effective method for the direct production of hydroxyfatty acids (HFAs) from free fatty acids (FFAs) using Escherichia coli. By employing fatty acid hydroxylase P450BM3and glucose dehydrogenase (GDH) to convert FFAs to HFAs, high-specificity production of C12 HFAs was achieved. By further knocking out the endogenous fadDgene of E. coli, an engineered strain capable of producing 702.3 mg/L C12 HFA was finally obtained, accounting for 92.9% of the total HFAs production, representing a higher titre reported in shake flask so far. This study provides an attractive strategy for increasing HFAs production in E. coliby increasing NADPH accumulation.

Induction of differentiation is a therapeutic strategy in neuroblastoma, a common pediatric cancer of the sympathetic nervous system. The homeobox protein HOXC9 is a key regulator of neuroblastoma differentiation. To gain a molecular understanding of the function of HOXC9 in promoting differentiation of neuroblastoma cells, we conducted a genome-wide analysis of the HOXC9-induced differentiation program by microarray gene expression profiling and chromatin immunoprecipitation in combination with massively parallel sequencing (ChIP-seq). Here we describe in detail the experimental system, methods, and quality control for the generation of the microarray and ChIP-seq data associated with our recent publication [1].

The purpose of the present study was to evaluate the pharmacokinetic interaction of vitexin rhamnoside (vitexin 2″-α-L-rhamnopyranosyl) and vitexin glucoside (vitexin 2″-β-D-glucopyranosyl) in rats by using a high performance liquid chromatography coupled with tandem mass spectrometry quantitative detection method (LC-MS/MS). The method was validated at the concentration range of 5 - 5000 ng/mL for both vitexin rhamnoside and vitexin glucoside with the regression equations Y = 0.00181X - 0.000955 (r> 0.998) and Y = 0.000788X - 0.000373 (r> 0.997), respectively. The methodological studies (including linearity, intra-assay / inter-assay accuracy and precision) of these two components were investigated. The pharmacokinetic parameters of these two components were compared, which demonstrated their pharmacokinetic variance, especially when they were administrated simultaneously.