Bioconjugation and Reaction-Induced Tumor Therapy via Alkynamide-Based Thiol-Yne Click Reaction.

Ferroptosis is associated with the occurrence and development of many diseases, which is the result of an imbalance in cellular metabolism and oxidation-reduction balance. Therefore, it is an effective therapeutic strategy that simultaneously regulating the intracellular oxidation-reduction system. Herein, a click reaction of alkynylamide with thiol groups in the presence of amine or in PBS (pH = 7.4) is developed, which can react efficiently with thiol substances, such as cysteine (Cys), glutathione (GSH), and bovine serum albumin (BSA). Notably, MBTB-PA, an aggregation-induced emission (AIE) photosensitizer with an alkynylamide unit, is synthesized and its intracellular behavior is visualized in situ by fluorescence imaging, demonstrating its excellent ability to target the endoplasmic reticulum. Furthermore, MBTB-PA reacted with proteins in tumor cells, consumed reducing substances, and triggered intracellular oxidative stress, resulting in cell death. Based on this reaction therapy strategy, click reaction is combined with photodynamic therapy to achieve effective killing of tumor cells by simultaneously raising the intracellular oxidative state and reducing the reductive state. This work not only develops an application of click reaction of alkynamide with thiol in bioconjugation and anti-tumor therapy, but also provides feasible ideas for organic reactions in the exploration of organisms.

SAL vibration estimation and compensation based on triangular interferometric signals.

Synthetic aperture Ladar (SAL) is an extension of synthetic aperture technology in the optical frequency band. Owing to the short wavelength of lasers, the system has high-resolution, high-data-rate, and refined imaging capabilities, which has potential in high-resolution observation fields such as ground observation and space target observation. However, the short wavelength of lasers also makes SAL severely sensitive to vibrations even on the micron order which cause azimuth defocusing and range cell migration. To address this problem, we establish a de-chirp signal model under vibration environment, and propose a vibration error estimation and compensation method using triangular interferometric signals. According to the symmetrical characteristics of triangular frequency modulated continuous wave (T-FMCW) and the time-frequency information introduced by the azimuthal vibration phase, we use a two-stage interferometry method to estimate instantaneous frequency introduced by the vibration errors that cause range cell migration. For the scenarios without obvious range cell migration, we use a one-stage interferometry method to estimate the instantaneous frequency. Subsequently, we establish a vibration compensation filter using the estimated instantaneous frequency to compensate for the vibration errors. We use two experiments to verify the effectiveness and superiority of the proposed method. The results show that the proposed method effectively eliminates range cell migration and azimuthal phase errors introduced by vibration errors, producing SAL imaging results with higher resolution than the conventional spectral correlation method.

Acoustofluidic manipulation for submicron to nanoparticles.

Particles, ranging from submicron to nanometer scale, can be broadly categorized into biological and non-biological types. Submicron-to-nanoscale bioparticles include various bacteria, viruses, liposomes, and exosomes. Non-biological particles cover various inorganic, metallic, and carbon-based particles. The effective manipulation of these submicron to nanoparticles, including their separation, sorting, enrichment, assembly, trapping, and transport, is a fundamental requirement for different applications. Acoustofluidics, owing to their distinct advantages, have emerged as a potent tool for nanoparticle manipulation over the past decade. Although recent literature reviews have encapsulated the evolution of acoustofluidic technology, there is a paucity of reports specifically addressing the acoustical manipulation of submicron to nanoparticles. This article endeavors to provide a comprehensive study of this topic, delving into the principles, apparatus, and merits of acoustofluidic manipulation of submicron to nanoparticles, and discussing the state-of-the-art developments in this technology. The discourse commences with an introduction to the fundamental theory of acoustofluidic control and the forces involved in nanoparticle manipulation. Subsequently, the working mechanism of acoustofluidic manipulation of submicron to nanoparticles is dissected into two parts, dominated by the acoustic wave field and the acoustic streaming field. A critical analysis of the advantages and limitations of different acoustofluidic platforms in nanoparticles control is presented. The article concludes with a summary of the challenges acoustofluidics face in the realm of nanoparticle manipulation and analysis, and a forecast of future development prospects.

C-type lectin 4 of Toxocara canis activates NF-ĸB and MAPK pathways by modulating NOD1/2 and RIP2 in murine macrophages in vitro.

Toxocara canis is a parasitic zoonose that is distributed worldwide and is one of the two pathogens causing toxocariasis. After infection, it causes serious public health and safety problems, which pose significant veterinary and medical challenges. To better understand the regulatory effects of T. canis infection on the host immune cells, murine macrophages (RAW264.7) were incubated with recombinant T. canis C-type lectin 4 (rTc-CTL-4) protein in vitro. The quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2), receptor-interacting protein 2 (RIP2), nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) on mRNA level and protein expression level in macrophages. Our results indicated that 10 µg/mL rTc-CTL-4 protein could modulate the expression of NOD1, NOD2, and RIP2 at both the transcriptional and translational levels. The protein translation levels of NF-κB, P-p65, p38, and P-p38 in macrophages were also modulated by rTc-CTL-4 protein. Macrophages were co-incubated with rTc-CTL-4 protein after siRNA silencing of NOD1, NOD2, and RIP2. The expression levels of NF-κB, P-p65, p38, and P-p38 were significantly changed compared with the negative control groups (Neg. Ctrl.). Taken together, rTc-CTL-4 protein seemed to act on NOD1/2-RIP2-NF-κB and MAPK signaling pathways in macrophages and might activate MAPK and NF-κB signaling pathways by regulating NOD1, NOD2, and RIP2. The insights from the above studies could contribute to our understanding of immune recognition and regulatory mechanisms of T. canis infection in the host animals.

Neural invertible variable-degree optical aberrations correction.

Optical aberrations of optical systems cause significant degradation of imaging quality. Aberration correction by sophisticated lens designs and special glass materials generally incurs high cost of manufacturing and the increase in the weight of optical systems, thus recent work has shifted to aberration correction with deep learning-based post-processing. Though real-world optical aberrations vary in degree, existing methods cannot eliminate variable-degree aberrations well, especially for the severe degrees of degradation. Also, previous methods use a single feed-forward neural network and suffer from information loss in the output. To address the issues, we propose a novel aberration correction method with an invertible architecture by leveraging its information-lossless property. Within the architecture, we develop conditional invertible blocks to allow the processing of aberrations with variable degrees. Our method is evaluated on both a synthetic dataset from physics-based imaging simulation and a real captured dataset. Quantitative and qualitative experimental results demonstrate that our method outperforms compared methods in correcting variable-degree optical aberrations.

Histone acetyltransferase 1 is a succinyltransferase for histones and non-histones and promotes tumorigenesis.

Lysine succinylation (Ksucc) is an evolutionarily conserved and widespread post-translational modification. Histone acetyltransferase 1 (HAT1) is a type B histone acetyltransferase, regulating the acetylation of both histone and non-histone proteins. However, the role of HAT1 in succinylation modulation remains unclear. Here, we employ a quantitative proteomics approach to study succinylation in HepG2 cancer cells and find that HAT1 modulates lysine succinylation on various proteins including histones and non-histones. HAT1 succinylates histone H3 on K122, contributing to epigenetic regulation and gene expression in cancer cells. Moreover, HAT1 catalyzes the succinylation of PGAM1 on K99, resulting in its increased enzymatic activity and the stimulation of glycolytic flux in cancer cells. Clinically, HAT1 is significantly elevated in liver cancer, pancreatic cancer, and cholangiocarcinoma tissues. Functionally, HAT1 succinyltransferase activity and the succinylation of PGAM1 by HAT1 play critical roles in promoting tumor progression in vitro and in vivo. Thus, we conclude that HAT1 is a succinyltransferase for histones and non-histones in tumorigenesis.

Repurposing Iron- and 2-Oxoglutarate-Dependent Oxygenases to Catalyze Olefin Hydration.

Mononuclear nonheme iron(II) and 2-oxoglutarate (Fe/2OG)-dependent oxygenases and halogenases are known to catalyze a diverse set of oxidative reactions, including hydroxylation, halogenation, epoxidation, and desaturation in primary metabolism and natural product maturation. However, their use in abiotic transformations has mainly been limited to C-H oxidation. Herein, we show that various enzymes of this family, when reconstituted with Fe(II) or Fe(III), can catalyze Mukaiyama hydration-a redox neutral transformation. Distinct from the native reactions of the Fe/2OG enzymes, wherein oxygen atom transfer (OAT) catalyzed by an iron-oxo species is involved, this nonnative transformation proceeds through a hydrogen atom transfer (HAT) pathway in a 2OG-independent manner. Additionally, in contrast to conventional inorganic catalysts, wherein a dinuclear iron species is responsible for HAT, the Fe/2OG enzymes exploit a mononuclear iron center to support this reaction. Collectively, our work demonstrates that Fe/2OG enzymes have utility in catalysis beyond the current scope of catalytic oxidation.

Effective Therapy of Drug-Resistant Bacterial Infection by Killing Planktonic Bacteria and Destructing Biofilms with Cationic Photosensitizer Based on Phosphindole Oxide.

Developing effective therapies to fight against biofilm-associated infection is extremely urgent. The complex environment of biofilm forces the bacteria to evade the elimination of antibiotics, resulting in recalcitrant chronic infections. To address this issue, a cationic antibacterial agent based on phosphindole oxide (ß-PM-PIO) is designed and prepared. The unique molecular structure endows ß-PM-PIO with aggregation-induced emission feature and efficient singlet oxygen generation ability. ß-PM-PIO shows excellent visual diagnostic function to planktonic bacteria and biofilm. In addition, owing to the synergistic effect of phototoxicity and dark toxicity, ß-PM-PIO can achieve superb antibacterial and antibiofilm performance against Gram-positive bacteria with less potential of developing drug resistance. Notably, ß-PM-PIO also holds excellent anti-infection capacity against drug-resistant bacteria in vivo with negligible side effects. This work offers a promising platform to develop advanced antibacterial agents against multidrug-resistant bacterial infection.

A Novel Detection Scheme in Image Domain for Multichannel Circular SAR Ground-Moving-Target Indication.

Circular synthetic aperture radar (CSAR), which can observe the region of interest for a long time and from multiple angles, offers the opportunity for moving-target detection (MTD). However, traditional MTD methods cannot effectively solve the problem of high probability of false alarm (PFA) caused by strong clutter. To mitigate this, a novel, three-step scheme combining clutter background extraction, multichannel clutter suppression, and the degree of linear consistency of radial velocity interferometric phase (DLRVP) test is proposed. In the first step, the spatial similarity of the scatterers and the correlation between sub-aperture images are fused to extract the strong clutter mask prior to clutter suppression. In the second step, using the data remaining after elimination of the background clutter in Step 1, an amplitude-based detector with higher processing gain is utilized to detect potential moving targets. In the third step, a novel test model based on DLRVP is proposed to further reduce the PFA caused by isolated strong scatterers. After the above processing, almost all false alarms are excluded. Measured data verified that the PFA of the proposed method is only 20% that of the comparison method, with improved detection of slow and weakly moving targets and with better robustness.

Vibration compensation method based on instantaneous ranging model for triangular FMCW ladar signals.

Triangular frequency-modulated continuous-wave (FMCW) laser radars (ladars) are extremely sensitive to vibration errors. An FMCW ladar 3D imaging system may suffer from severe vibrations and can use only one-period echoes for the ranging of each observation spot; consequently, it can provide only few measurement results. These vibrations may cause large errors because conventional vibration compensation methods are ineffective when applied to fast disturbances with limited measurement results. To solve this problem, we analyze the influence of vibrations on FMCW ladar ranging and propose a vibration compensation method based on an instantaneous ranging model for one-period triangular FMCW ladar signals. We first use a synchrosqueezing wavelet transform to extract time-frequency curves of the up- and down-dechirp signals and then build an instantaneous ranging model that can characterize local vibration errors. Based on the instantaneous ranges, we remove the disturbance vibration errors by taking the mean values of the instantaneous ranges and obtain the target range by using the triangular relations of the up and down observations. Experiments based on synthetic and real data verify the effectiveness of the proposed method and its superiority over the three-point method and Doppler shift method in compensating for vibrations with different frequencies and noise levels.

Extended GLRT Detection of Moving Targets for Multichannel SAR Based on Generalized Steering Vector.

A generalized likelihood ratio test (GLRT) with the constant false alarm rate (CFAR) property was recently developed for adaptive detection of moving targets in focusing synthetic aperture radar (SAR) images. However, in the multichannel SAR-ground moving-target indication (SAR-GMTI) system, image defocus is inevitable, which will remarkably degrade the performance of the GLRT detector, especially for the lower radar cross-section (RCS) and slower radial velocity moving targets. To address this issue, based on the generalized steering vector (GSV), an extended GLRT detector is proposed and its performance is evaluated by the optimum likelihood ratio test (LRT) in the Neyman-Pearson (NP) criterion. The joint data vector formulated by the current cell and its adjacent cells is used to obtain the GSV, and then the extended GLRT is derived, which coherently integrates signal and accomplishes moving-target detection and parameter estimation. Theoretical analysis and simulated SAR data demonstrate the effectiveness and robustness of the proposed detector in the defocusing SAR images.

A Coherence Improvement Method Based on Sub-Aperture InSAR for Human Activity Detection.

Human activity detection plays an important role in social security monitoring. Since human activity is very weak, it is necessary to employ the repeat-pass Interferometric Synthetic Aperture Radar (InSAR) technique to detect the potential activity between two data acquisitions; a high level of coherence is required for detection. With the object of detecting human activity of interest, this paper presents a coherence improvement approach based on sub-aperture InSAR for human activity detection. Different sub-apertures contain different scattering information of the target, as they represent the backscatter of the target from a different range of angles. Integrating corresponding sub-aperture interferometric results can improve the coherence between two complex images compared to the entire synthetic aperture, as well as removing a little disturbance in some circumstances. To validate the method presented in this paper, the actual airborne Ka-band frequency modulated continuous wave (FMCW) InSAR data acquired by the Aerospace Information Research Institute, Chinese Academy of Sciences (AIRCAS) are utilized. The experimental results demonstrate that the proposed method can effectively improve the coherence between two complex SAR images and can validly detect human activity of interest.

Asymmetric Total Syntheses of 8,9-Seco-ent-kaurane Diterpenoids Enabled by an Electrochemical ODI-[5+2] Cascade.

An electrochemical ODI-[5+2] cascade reaction was developed which enables the rapid assembly of diversely functionalized bicyclo[3.2.1]octadienones from sensitive ethynylphenols. By combining a directed retro-aldol/aldol process, a [2,3]-sigmatropic rearrangement, and an Al(O-iPr)3 -promoted reductive 1,3-transposition, the asymmetric total syntheses of five 8,9-seco-ent-kauranoids-(-)-shikoccin, (-)-O-methylshikoccin, (-)-epoxyshikoccin, (+)-O-methylepoxyshikoccin, and (+)-rabdo-hakusin-have been achieved in a concise and efficient manner.

Motivational climate, need satisfaction, self-determined motivation, and physical activity of students in secondary school physical education in China.

BACKGROUND: On the basis of the integration constructs from self-determination theory (SDT) and achievement goal theory (AGT), this study aims to investigate the relationship among classroom motivational climate from four perspectives (i.e. autonomy support, relatedness support, task-involving climate and ego-involving climate), three psychological needs (i.e. autonomy, competence and relatedness), self-determined motivation and physical activity (PA) in secondary physical education (PE). METHODS: Participants consisted of 1186 Chinese students aged 11 to 16 years from three secondary schools in Shanghai. Accelerometers were utilized to measure moderate to vigorous physical activity (MVPA). Questionnaires were used to measure SDT variables (i.e. classroom motivational climate, perceived competence, autonomy, relatedness and self-determined motivation). Structural equation modelling (SEM) was adopted to analyse the hypothesised relationship. RESULTS: SEM analysis revealed that task-involving climate and autonomy support were positively associated with autonomy, relatedness and competence. Relatedness support was positively related with autonomy and relatedness, whereas ego-involving climate was only associated with competence. The three psychological needs positively affected self-determined motivation, and self-determined motivation positively affected the MVPA time of secondary school students in PE lessons. CONCLUSION: These findings support a model of motivation that integrates SDT and AGT, provides new insight into understanding MVPA in Chinese PE, and establishes a solid basis for intervention research.

Coherent Markov Random Field-Based Unreliable DSM Areas Segmentation and Hierarchical Adaptive Surface Fitting for InSAR DEM Reconstruction.

A digital elevation model (DEM) can be obtained by removing ground objects, such as buildings, in a digital surface model (DSM) generated by the interferometric synthetic aperture radar (InSAR) system. However, the imaging mechanism will cause unreliable DSM areas such as layover and shadow in the building areas, which seriously affect the elevation accuracy of the DEM generated from the DSM. Driven by above problem, this paper proposed a novel DEM reconstruction method. Coherent Markov random field (CMRF) was first used to segment unreliable DSM areas. With the help of coherence coefficients and residue information provided by the InSAR system, CMRF has shown better segmentation results than traditional traditional Markov random field (MRF) which only use fixed parameters to determine the neighborhood energy. Based on segmentation results, the hierarchical adaptive surface fitting (with gradually changing the grid size and adaptive threshold) was set up to locate the non-ground points. The adaptive surface fitting was superior to the surface fitting-based method with fixed grid size and threshold of height differences. Finally, interpolation based on an inverse distance weighted (IDW) algorithm combining coherence coefficient was performed to reconstruct a DEM. The airborne InSAR data from the Institute of Electronics, Chinese Academy of Sciences has been researched, and the experimental results show that our method can filter out buildings and identify natural terrain effectively while retaining most of the terrain features.

Analysis and compensation of telescopes' gaps effect on aperture synthesis in a multi-channel synthetic aperture ladar system.

The azimuth multi-channel synthetic aperture ladar (SAL), which arranges multiple telescopes along the flight direction of the platform, transmits signals through a single telescope and receives echoes by multiple telescopes simultaneously to obtain data. The aperture synthesis technology, which has the ability to achieve high resolution through multiple small telescopes, is applied to the multi-channel SAL system to realize the reconstruction of the complete azimuth Doppler spectrum in a short observation time. However, there are gaps inevitably between telescopes, which degrade the results of aperture synthesis. In this work, the effect of gaps on the instantaneous Doppler spectrum of each channel and the influence on the result of the azimuth impulse compression after aperture synthesis are analyzed. In addition, an estimation method of gaps based on the phase errors between channels is proposed to reduce the influence. The estimation accuracy of the proposed method is analyzed, and the effectiveness of the method is verified with simulations. The estimated gaps are used to compensate for the phase discontinuity of the azimuth signal after aperture synthesis caused by gaps. The method improves the result of aperture synthesis and reduces the side-lobe of the azimuth impulse compression after aperture synthesis.

Synthesis of 5-Amino and 3,5-Diamino Substituted 1,2,4-Thiadiazoles by I2-Mediated Oxidative N-S Bond Formation.

An oxidative N-S bond formation reaction has been established for 1,2,4-thiadiazole synthesis employing molecular iodine as the sole oxidant. The features of the present reaction include no use of transition metals, mild reaction conditions, simple operation, and short reaction time. This versatile synthetic approach is broadly applicable to a variety of imidoyl and guanyl thiourea substrates to produce 5-amino and 3,5-diamino substituted 1,2,4-thiadiazole derivatives, respectively, in an efficient and scalable fashion.

Synthesis of Quinazolines from N,N'-Disubstituted Amidines via I2/KI-Mediated Oxidative C-C Bond Formation.

An I2/KI-promoted oxidative C-C bond formation reaction from C(sp3)-H and C(sp2)-H bonds has been used to construct quinazoline skeletons from N,N'-disubstituted amidines. The required substrates are readily prepared from the corresponding acyl chlorides, anilines, and alkyl/benzylamines by sequential amidation, chlorination, and amination reactions. Under the optimal oxidative cyclization conditions, all these amidines were conveniently transformed into the expected products in moderate to good yields. This practical and environmentally benign approach works well with crude amidine intermediates and can also be carried out on a gram scale.

Multi-Channel Capacitive Sensor Arrays.

In this paper, multi-channel capacitive sensor arrays based on microstrip band-stop filters are studied. The sensor arrays can be used to detect the proximity of objects at different positions and directions. Each capacitive sensing structure in the array is connected to an inductive element to form resonance at different frequencies. The resonances are designed to be isolated in the frequency spectrum, such that the change in one channel does not affect resonances at other channels. The inductive element associated with each capacitive sensor can be surface-mounted inductors, integrated microstrip inductors or metamaterial-inspired structures. We show that by using metamaterial split-ring structures coupled to a microstrip line, the quality factor of each resonance can be greatly improved compared to conventional surface-mounted or microstrip meander inductors. With such a microstrip-coupled split-ring design, more sensing elements can be integrated in the same frequency spectrum, and the sensitivity can be greatly improved.

A MADS-box gene NtSVP regulates pedicel elongation by directly suppressing a KNAT1-like KNOX gene NtBPL in tobacco (Nicotiana tabacum L.).

Optimal inflorescence architecture is important for plant reproductive success by affecting the ultimate number of flowers that set fruits and for plant competitiveness when interacting with biotic or abiotic conditions. The pedicel is one of the key contributors to inflorescence architecture diversity. To date, knowledge about the molecular mechanisms of pedicel development is derived from Arabidopsis. Not much is known regarding other plants. Here, an SVP family MADS-box gene, NtSVP, in tobacco (Nicotiana tabacum) that is required for pedicel elongation was identified. It is shown that knockdown of NtSVP by RNA interference (RNAi) caused elongated pedicels, while overexpression resulted in compact inflorescences with much shortened pedicels. Moreover, an Arabidopsis BREVIPEDECELLUS/KNAT1 homologue NtBP-Like (NtBPL) was significantly up-regulated in NtSVP-RNAi plants. Disruption of NtBPL decreased pedicel lengths and shortened cortex cells. Consistent with the presence of a CArG-box at the NtBPL promoter, the direct binding of NtSVP to the NtBPL promoter was demonstrated by yeast one-hybrid assay, electrophoretic mobility shift assay, and dual-luciferase assay, in which NtSVP may act as a repressor of NtBPL. Microarray analysis showed that down-regulation of NtBPL resulted in differential expression of genes associated with a number of hormone biogenesis and signalling genes such as those for auxin and gibberellin. These findings together suggest the function of a MADS-box transcription factor in plant pedicel development, probably via negative regulation of a BP-like class I KNOX gene. The present work thus postulates the conservation and divergence of the molecular regulatory pathways underlying the development of plant inflorescence architecture.