Transgenic mice lacking FGF15/19-SHP phosphorylation display altered bile acids and gut bacteria, promoting nonalcoholic fatty liver disease.

Dysregulated bile acid (BA)/lipid metabolism and gut bacteria dysbiosis are tightly associated with the development of obesity and non-alcoholic fatty liver disease (NAFLD). The orphan nuclear receptor, Small Heterodimer Partner (SHP/NR0B2), is a key regulator of BA/lipid metabolism, and its gene-regulating function is markedly enhanced by phosphorylation at Thr-58 mediated by a gut hormone, fibroblast growth factor-15/19 (FGF15/19). To investigate the role of this phosphorylation in whole-body energy metabolism, we generated transgenic SHP-T58A knock-in mice. Compared with wild-type (WT) mice, the phosphorylation-defective SHP-T58A mice gained weight more rapidly with decreased energy expenditure and increased lipid/BA levels. This obesity-prone phenotype was associated with the upregulation of lipid/BA synthesis genes and downregulation of lipophagy/ß-oxidation genes. Mechanistically, defective SHP phosphorylation selectively impaired its interaction with LRH-1, resulting in de-repression of SHP/LRH-1 target BA/lipid synthesis genes. Remarkably, BA composition and selective gut bacteria which are known to impact obesity, were also altered in these mice. Upon feeding a high-fat diet, fatty liver developed more severely in SHP-T58A mice compared to WT mice. Treatment with antibiotics substantially improved the fatty liver phenotypes in both groups but had greater effects in the T58A mice so that the difference between the groups was largely eliminated. These results demonstrate that defective phosphorylation at a single nuclear receptor residue can impact whole-body energy metabolism by altering BA/lipid metabolism and gut bacteria, promoting complex metabolic disorders like NAFLD. Since posttranslational modifications generally act in gene- and context-specific manners, the FGF15/19-SHP phosphorylation axis may allow more targeted therapy for NAFLD.

Efficient Silver(I)-Containing I-Motif DNA Hybrid Catalyst for Enantioselective Diels-Alder Reactions.

The inherent chiral structures of DNA serve as attractive scaffolds to construct DNA hybrid catalysts for valuable enantioselective transformations. Duplex and G-quadruplex DNA-based enantioselective catalysis has made great progress, yet novel design strategies of DNA hybrid catalysts are highly demanding and atomistic analysis of active centers is still challenging. DNA i-motif structures could be finely tuned by different cytosine-cytosine base pairs, providing a new platform to design DNA catalysts. Herein, we found that a human telomeric i-motif DNA containing cytosine-silver(I)-cytosine (C-Ag+-C) base pairs interacting with Cu(II) ions (i-motif DNA(Ag+)/Cu2+) could catalyze Diels-Alder reactions with full conversions and up to 95 % enantiomeric excess. As characterized by various physicochemical techniques, the presence of Ag+ is proved to replace the protons in hemiprotonated cytosine-cytosine (C : C+) base pairs and stabilize the DNA i-motif to allow the acceptance of Cu(II) ions. The i-motif DNA(Ag+)/Cu2+ catalyst shows about 8-fold rate acceleration compared with DNA and Cu2+. Based on DNA mutation experiments, thermodynamic studies and density function theory calculations, the catalytic center of Cu(II) ion is proposed to be located in a specific loop region via binding to one nitrogen-7 atom of an unpaired adenine and two phosphate-oxygen atoms from nearby deoxythymidine monophosphate and deoxyadenosine monophosphate, respectively.

Pseudomonas benzopyrenica sp. nov., isolated from soil, exhibiting high-efficiency degradation of benzo(a)pyrene.

A Gram-negative, yellow-pigmented, aerobic and rod-shaped bacterium, designated as strain BaP3T, was isolated from the soil. Strain BaP3T grew at 16-37℃ (optimum, 30 °C) and pH 6.0-8.0 (optimum, pH 7.0). Additionally, strain BaP3T could tolerate NaCl concentrations in the range 0-6 % (optimum, 1%). Moreover, strain BaP3T was motile by flagella. The phylogenetic analysis of 16S rRNA sequences showed that strain BaP3T belonged to the genus Pseudomonas, and the sequence was most closely related to Pseudomonas oryzihabitans CGMCC 1.3392T and Pseudomonas psychrotolerans DSM 15758T, with 99.66 % sequence similarity. Pseudomonas rhizoryzae RY24T was the next closely related species, exhibiting 99.38 % 16S rRNA gene sequence similarity. The DNA-DNA hybridization and average nucleotide identity values between strain BaP3T and its closely related types were below 50 and 92 %, respectively. Both results were below the cut-off for species distinction. The genomic DNA G+C content of strain BaP3T was 65.30 mol%. The predominant quinone in strain BaP3T was identified as ubiquinone Q-9. The major cellular fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and C16 : 0. These results indicated that strain BaP3T represents a novel species in the genus Pseudomonas. The type strain is BaP3T (CCTCC AB 2022379T=JCM 35914T), for which the name Pseudomonas benzopyrenica sp. nov. is proposed.

Cyclic Dinucleotide-Based Enantioselective Fluorination in Water.

The diverse structures of DNA serve as potent chiral scaffolds for DNA-based asymmetric catalysis, yet in most cases tens to hundreds of nucleotides in DNA hybrid catalysts hinder the deep insight into their structure-activity relationship. Owing to the structural simplicity and design flexibility of nucleotides, nucleotide-based catalysts have been emerging as a promising way to obtain fine structural information and understand the catalytic mechanisms. Herein, we found that a cyclic dinucleotide of cyclic di-AMP (c-di-AMP) and 1,10-phenanthroline copper(II) nitrate (Cu(phen)(NO3)2) are assembled to a c-di-AMP-based catalyst (c-di-AMP/Cu(phen)(NO3)2), which could fast achieve enantioselective fluorination in water with 90-99% yields and up to 90% enantiomeric excess (ee). The host-guest interaction between c-di-AMP and Cu(phen)(NO3)2 has been proposed mainly in a supramolecular interaction mode as evidenced by spectroscopic techniques of ultraviolet-visible, fluorescence, circular dichroism, and nuclear magnetic resonance. Cu(phen)(NO3)2 tightly binds to c-di-AMP with a binding constant of 1.7 ± 0.3 × 105 M-1, and the assembly of c-di-AMP/Cu(phen)(NO3)2 shows a modest rate enhancement to carbon-fluorine bond formations as supported by kinetic studies.

Automatic Seizure Detection Based on Stockwell Transform and Transformer.

Epilepsy is a chronic neurological disease associated with abnormal neuronal activity in the brain. Seizure detection algorithms are essential in reducing the workload of medical staff reviewing electroencephalogram (EEG) records. In this work, we propose a novel automatic epileptic EEG detection method based on Stockwell transform and Transformer. First, the S-transform is applied to the original EEG segments, acquiring accurate time-frequency representations. Subsequently, the obtained time-frequency matrices are grouped into different EEG rhythm blocks and compressed as vectors in these EEG sub-bands. After that, these feature vectors are fed into the Transformer network for feature selection and classification. Moreover, a series of post-processing methods were introduced to enhance the efficiency of the system. When evaluating the public CHB-MIT database, the proposed algorithm achieved an accuracy of 96.15%, a sensitivity of 96.11%, a specificity of 96.38%, a precision of 96.33%, and an area under the curve (AUC) of 0.98 in segment-based experiments, along with a sensitivity of 96.57%, a false detection rate of 0.38/h, and a delay of 20.62 s in event-based experiments. These outstanding results demonstrate the feasibility of implementing this seizure detection method in future clinical applications.

Insight into the High-Efficiency Benzo(a)pyrene Degradation Ability of Pseudomonas benzopyrenica BaP3 and Its Application in the Complete Bioremediation of Benzo(a)pyrene.

Polycyclic aromatic hydrocarbons (PAHs) are common carcinogens. Benzo(a)pyrene is one of the most difficult high-molecular-weight (HMW) PAHs to remove. Biodegradation has become an ideal method to eliminate PAH pollutants from the environment. The existing research is mostly limited to low-molecular-weight PAHs; there is little understanding of HMW PAHs, particularly benzo(a)pyrene. Research into the biodegradation of HMW PAHs contributes to the development of microbial metabolic mechanisms and also provides new systems for environmental treatments. Pseudomonas benzopyrenica BaP3 is a highly efficient benzo(a)pyrene-degrading strain that is isolated from soil samples, but its mechanism of degradation remains unknown. In this study, we aimed to clarify the high degradation efficiency mechanism of BaP3. The genes encoding Rhd1 and Rhd2 in strain BaP3 were characterized, and the results revealed that rhd1 was the critical factor for high degradation efficiency. Molecular docking and enzyme activity determinations confirmed this conclusion. A recombinant strain that could completely mineralize benzo(a)pyrene was also proposed for the first time. We explained the mechanism of the high-efficiency benzo(a)pyrene degradation ability of BaP3 to improve understanding of the degradation mechanism of highly toxic PAHs and to provide new solutions to practical applications via synthetic biology.

A bispecific antibody targeting HER2 and PD-L1 inhibits tumor growth with superior efficacy.

Activation of the programmed cell death protein 1 and programmed cell death ligand 1 (PD-1/PD-L1) signaling axis plays important roles in intrinsic or acquired resistance to human epidermal growth factor receptor 2 (HER2)-directed therapies in the clinic. Therefore, therapies simultaneously targeting both HER2 and PD-1/PD-L1 signaling pathways are of great significance. Here, aiming to direct the anti-PD-L1 responses toward HER2-expressing tumor cells, we constructed a humanized bispecific IgG1 subclass antibody targeting both HER2 and PD-L1 (HER2/PD-L1; BsAb), which displayed satisfactory purity, thermostability, and serum stability. We found that BsAb showed enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) activity in vitro. In the late phase of peripheral blood mononuclear cell (PBMC)-humanized HER2+ tumor xenograft models, BsAb showed superior therapeutic efficacies as compared with monoclonal antibodies (mAbs) or combination treatment strategies. In cynomolgus monkeys, BsAb showed favorable pharmacokinetics and toxicity profiles when administered at a 10 mg/kg dosage. Thus, HER2/PD-L1 BsAb was demonstrated as a potentially effective option for managing HER2+ and trastuzumab-resistant tumors in the clinic. We propose that the enhanced antitumor activities of BsAb in vivo may be due to direct inhibition of HER2 signaling or activation of T cells.

Shear-unlimited common-path speckle interferometer.

A single-aperture common-path speckle interferometer with an unlimited shear amount is developed. This unlimited shear amount is introduced when a Wollaston prism is placed near the Fourier plane of a common-path interferometer, which is built by using a quasi-${4f}$4f imaging system. The fundamentals of the shear amount and the spatial carrier frequency generation are analyzed mathematically, and the theoretical predictions are validated by a static experiment. Mode-I fracture experiments through the three-point bending are conducted to prove the feasibility and the capability of this method in full-field strain measurement with various shear amounts. A remarkable feature of this setup is that no tilt is required between the optical components to produce the unlimited shear amount in off-axis holography.

Highly Efficient Cyclic Dinucleotide Based Artificial Metalloribozymes for Enantioselective Friedel-Crafts Reactions in Water.

The diverse secondary structures of nucleic acids are emerging as attractive chiral scaffolds to construct artificial metalloenzymes (ArMs) for enantioselective catalysis. DNA-based ArMs containing duplex and G-quadruplex scaffolds have been widely investigated, yet RNA-based ArMs are scarce. Here we report that a cyclic dinucleotide of c-di-AMP and Cu2+ ions assemble into an artificial metalloribozyme (c-di-AMP⋅Cu2+ ) that enables catalysis of enantioselective Friedel-Crafts reactions in aqueous media with high reactivity and excellent enantioselectivity of up to 97 % ee. The assembly of c-di-AMP⋅Cu2+ gives rise to a 20-fold rate acceleration compared to Cu2+ ions. Based on various biophysical techniques and density function theory (DFT) calculations, a fine coordination structure of c-di-AMP⋅Cu2+ metalloribozyme is suggested in which two c-di-AMP form a dimer scaffold and the Cu2+ ion is located in the center of an adenine-adenine plane through binding to two N7 nitrogen atoms and one phosphate oxygen atom.

Real-time dual-sensitive shearography for simultaneous in-plane and out-of-plane strain measurements.

A real-time, dual-sensitive shearography system using a single-wavelength laser was developed for simultaneous and dynamic in-plane and out-of-plane strain measurements. The shearography system is capable of measuring crack-tip deformation fields quantitatively. A spatial multiplexing technique based on Fourier transform is employed for simultaneous and dynamic multi-component phase retrieval. Two slit spatial filters and a common-path shearing interferometer are used to obtain an improved phase quality for crack-tip deformation measurements. Mode-I fracture experiments under three-point bending were conducted to validate the feasibility and the capability of this method.

Glucose-induced changes in the bacterial communities of mine tailings at different acidification stages.

Ecological restoration technologies applied to tailings can influence the associated bacterial communities. However, it is unknown if the shifts in these bacterial communities are caused by increased organic carbon. Glucose-induced respiration and high-throughput sequencing were used to assess the microbial activity and bacterial communities, respectively. Glucose addition increased the microbial activity, and glucose + ammonium nitrate addition resulted in slightly higher CO2 emission than did glucose addition alone, suggesting that carbon and nitrogen limited microbial community growth. In neutral pH tailings, the bacterial taxa that increased by glucose addition were assigned to the phyla Proteobacteria, Acidobacteria, Actinobacteria, Bacteroidetes, Firmicutes, and Planctomycetes. However, the bacterial taxa that increased by glucose addition in acidic tailings only belonged to the phylum Actinobacteria (maximum increase of 43.78%). In addition, the abundances of the total nitrogen-fixing genera and of the genus Arthrobacter (representing approximately 97.89% of the total nitrogen-fixing genera) increased by glucose addition in acidic tailings (maximum increase of 46.98%). In contrast, the relative abundances of the total iron- and (or) sulfur-oxidizing bacteria decreased (maximum decrease of 10.41%) in response to the addition of glucose. These findings indicate that the addition of organic carbon is beneficial to the development of bacterial communities in mine tailings.

Broadband static Fourier transform mid-infrared spectrometer.

For applications where only moderate spectral resolution is required, static Fourier transform infrared spectrometers (sFTS) offer a comparatively cost-effective alternative to classical scanning instruments. In this paper, we present an sFTS based on a single-mirror interferometer using only standard optical components and an uncooled microbolometer array. Because the instrument features concave mirrors rather than lenses, dispersion effects can be minimized. This enables broadband operation in the mid-infrared range from 2800 cm-1 to 600 cm-1 at a spectral resolution of 12 cm-1. In addition, the design guarantees comparatively high light throughput and can potentially be designed for increased temperature stability. Alongside a simulation of the temperature- and wavenumber-dependent behavior of the system, we provide a proof of principle of the proposed design by means of experimental results.

Dual-directional shearography based on a modified common-path configuration using spatial phase shift.

This paper describes a dual-directional shearography system to address the issue of two-dimensional characterization of the surface strain. A common-path configuration coupled with an additional light path is used to provide the shearing in two directions. One of the three interfering beams is shared by both directional shearograms to improve the light efficiency and enhance the robustness of the system. The two directional shearograms are carried by different spatial carriers to distinguish one from the other. The spatial carrier is introduced by the single-aperture-lens Wollaston prism configuration. Rather than the conventional method in which the aperture is fixed at the front focal point of the imaging lens, a general case is considered by introducing a variable distance between the aperture and the imaging lens. The influence of the aperture-lens distance on the spatial carrier is then analyzed, which enables the separate control of the shearing amount and the spatial carrier. Two types of dual-directional shearography are presented to demonstrate the feasibility and the flexibility of the system. Type I is the simultaneous dual lateral shearography in orthogonal directions, and Type II is the simultaneous lateral and radial shearography. The spatial carrier introduced by the single-aperture-lens Wollaston prism configuration is discussed, and a configuration in which the Wollaston prism and the aperture are located at different sides of the lens is recommended for further shearography applications.

Dermal Tattoo Biosensors for Colorimetric Metabolite Detection.

Tattooing is a ubiquitous body modification involving the injection of ink and/or dye pigments into the dermis. Biosensors in the form of tattoos can be used to monitor metabolites in interstitial fluid. Here, minimally invasive, injectable dermal biosensors were developed for measuring pH, glucose, and albumin concentrations. The dermal pH sensor was based on methyl red, bromothymol blue, and phenolphthalein, which responded to a pH range from 5.0 to 9.0. The dermal glucose sensor consisted of glucose oxidase, 3,3',5,5'-tetramethylbenzidine, and peroxidase that detected concentrations up to 50.0 mmol L-1 . The dermal albumin sensor consisted of 3',3'',5',5''-tetrachlorophenol-3,4,5,6-tetrabromosulfophthalein to measure concentrations up to 5.0 g L-1 . The sensors were multiplexed in ex vivo skin tissue and quantitative readouts were obtained using a smartphone camera. These sensors can be used to manage of acid-base homeostasis, diabetes, and liver failure in point-of-care settings.

A DFT Calculation of Fluoride-Doped TiO2 Nanotubes for Detecting SF6 Decomposition Components.

Gas insulated switchgear (GIS) plays an important role in the transmission and distribution of electric energy. Detecting and analyzing the decomposed components of SF6 is one of the important methods to realize the on-line monitoring of GIS equipment. In this paper, considering the performance limits of intrinsic TiO2 nanotube gas sensor, the adsorption process of H2S, SO2, SOF2 and SO2F2 on fluoride-doped TiO2 crystal plane was simulated by the first-principle method. The adsorption mechanism of these SF6 decomposition components on fluorine-doped TiO2 crystal plane was analyzed from a micro perspective. Calculation results indicate that the order of adsorption effect of four SF6 decomposition components on fluoride-doped TiO2 crystal plane is H2S > SO2 > SOF2 > SO2F2. Compared with the adsorption results of intrinsic anatase TiO2 (101) perfect crystal plane, fluorine doping can obviously enhance the adsorption ability of TiO2 (101) crystal plane. Fluorine-doped TiO2 can effectively distinguish and detect the SF6 decomposition components based on theoretical analysis.

Investigation of Gas-Sensing Property of Acid-Deposited Polyaniline Thin-Film Sensors for Detecting H2S and SO2.

Latent insulation defects introduced in manufacturing process of gas-insulated switchgears can lead to partial discharge during long-time operation, even to insulation fault if partial discharge develops further. Monitoring of decomposed components of SF6, insulating medium of gas-insulated switchgear, is a feasible method of early-warning to avoid the occurrence of sudden fault. Polyaniline thin-film with protonic acid deposited possesses wide application prospects in the gas-sensing field. Polyaniline thin-film sensors with only sulfosalicylic acid deposited and with both hydrochloric acid and sulfosalicylic acid deposited were prepared by chemical oxidative polymerization method. Gas-sensing experiment was carried out to test properties of new sensors when exposed to H2S and SO2, two decomposed products of SF6 under discharge. The gas-sensing properties of these two sensors were compared with that of a hydrochloric acid deposited sensor. Results show that the hydrochloric acid and sulfosalicylic acid deposited polyaniline thin-film sensor shows the most outstanding sensitivity and selectivity to H2S and SO2 when concentration of gases range from 10 to 100 µL/L, with sensitivity changing linearly with concentration of gases. The sensor also possesses excellent long-time and thermal stability. This research lays the foundation for preparing practical gas-sensing devices to detect H2S and SO2 in gas-insulated switchgears at room temperature.

Approach for designing and developing high-precision integrative systems for strip flatness detection.

In this paper, we propose an approach for designing and developing high-precision integrative systems for strip flatness detection. Algorithms are developed for camera calibration, which are more accurate than the general method calculating all the camera parameters. On the basis of this method, a detection system is developed including an integrative device for easy calculation and repeated usage. On-site experiment results confirm that the proposed method works well under hostile environmental conditions in mills.

Analysis of the Sensitivity of K-Type Molecular Sieve-Deposited MWNTs for the Detection of SF6 Decomposition Gases under Partial Discharge.

Sulfur hexafluoride (SF6) is widely utilized in gas-insulated switchgear (GIS). However, part of SF6 decomposes into different components under partial discharge (PD) conditions. Previous research has shown that the gas responses of intrinsic and 4 Å-type molecular sieve-deposited multi-wall carbon nanotubes (MWNTs) to SOF2 and SO2F2, two important decomposition components of SF6, are not obvious. In this study, a K-type molecular sieve-deposited MWNTs sensor was developed. Its gas response characteristics and the influence of the mixture ratios of gases on the gas-sensing properties were studied. The results showed that, for sensors with gas mixture ratios of 5:1, 10:1, and 20:1, the resistance change rate increased by nearly 13.0% after SOF2 adsorption, almost 10 times that of MWNTs sensors, while the sensors' resistance change rate with a mixture ratio of 10:1 reached 17.3% after SO2F2 adsorption, nearly nine times that of intrinsic MWNT sensors. Besides, a good linear relationship was observed between concentration of decomposition components and the resistance change rate of sensors.

Gas sensitivity and sensing mechanism studies on Au-doped TiO2 nanotube arrays for detecting SF6 decomposed components.

The analysis to SF6 decomposed component gases is an efficient diagnostic approach to detect the partial discharge in gas-insulated switchgear (GIS) for the purpose of accessing the operating state of power equipment. This paper applied the Au-doped TiO2 nanotube array sensor (Au-TiO2 NTAs) to detect SF6 decomposed components. The electrochemical constant potential method was adopted in the Au-TiO2 NTAs' fabrication, and a series of experiments were conducted to test the characteristic SF6 decomposed gases for a thorough investigation of sensing performances. The sensing characteristic curves of intrinsic and Au-doped TiO2 NTAs were compared to study the mechanism of the gas sensing response. The results indicated that the doped Au could change the TiO2 nanotube arrays' performances of gas sensing selectivity in SF6 decomposed components, as well as reducing the working temperature of TiO2 NTAs.

Epileptic Seizure Prediction Using Spatiotemporal Feature Fusion on EEG.

Electroencephalography (EEG) plays a crucial role in epilepsy analysis, and epileptic seizure prediction has significant value for clinical treatment of epilepsy. Currently, prediction methods using Convolutional Neural Network (CNN) primarily focus on local features of EEG, making it challenging to simultaneously capture the spatial and temporal features from multi-channel EEGs to identify the preictal state effectively. In order to extract inherent spatial relationships among multi-channel EEGs while obtaining their temporal correlations, this study proposed an end-to-end model for the prediction of epileptic seizures by incorporating Graph Attention Network (GAT) and Temporal Convolutional Network (TCN). Low-pass filtered EEG signals were fed into the GAT module for EEG spatial feature extraction, and followed by TCN to capture temporal features, allowing the end-to-end model to acquire the spatiotemporal correlations of multi-channel EEGs. The system was evaluated on the publicly available CHB-MIT database, yielding segment-based accuracy of 98.71%, specificity of 98.35%, sensitivity of 99.07%, and F1-score of 98.71%, respectively. Event-based sensitivity of 97.03% and False Positive Rate (FPR) of 0.03/h was also achieved. Experimental results demonstrated this system can achieve superior performance for seizure prediction by leveraging the fusion of EEG spatiotemporal features without the need of feature engineering.