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We proposed a non-contact photoacoustic (PA) detection method using spectral domain optical coherence tomography (SDOCT). Two interference spectrums (A-lines) were acquired before and after the PA excitation with SDOCT. PA signal propagated within the sample causing the vibration. The vibration inner the sample introduced phase change between the acquired two A-lines. Thus, the PA signal can be detected by evaluating the difference in phase between the two A-lines. Based on the method, an OCT-PAM dual-mode imaging system was constructed. In the system, SDOCT served as the detection unit for PAM. Thus, the combination of the two imaging modalities was simplified. Another advantage of the system is that it realizes non-contact all-optic detection, which is attractive for biomedical imaging. Using the system, we imaged phantoms of carbon fibers, asparagus leaves and human hairs. Furthermore, the cortical vasculature of rat was imaged in vivo and the flow status was evaluated quantitatively.

Hexavalent chromium [Cr(VI)] exists widely in occupational environments. The mechanistic target of rapamycin (mTOR) has been well-documented to regulate autophagy negatively. However, we found that low concentration of Cr(VI) (0.2 μM) elevated both mTOR and autophagy and promote cell survival. Conversely, high concentration of Cr(VI) (6 μM) caused cell death by inhibiting mTOR and subsequently inducing autophagy. Tunicamycin (Tm), as an Endoplasmic reticulum (ER) stress activator was used to induce mild ER stress at 0.1 μg/ml and it activated both autophagy and mTOR, which also caused cell migration in a similar manner to that observed with low concentration of Cr(VI). Severe ER stress caused by Tm (2 μg/ml) decreased mTOR, increased autophagy and then inhibited cell migration, which was the same as 6 μM Cr(VI) treatment, although Cr(VI) in high concentration inhibited ER stress. Activating transcription factor 4 (ATF4), a downstream target of ER stress, only increased under mild ER stress but decreased under severe ER stress and 6 μM Cr(VI) treatment. Chromatin immunoprecipitation (ChIP) experiment indicated that ATF4 could bind to the promoter of ATG4B and AKT1. To sum up, our data revealed that mild ER stress induced by low concentration of Cr(VI) could enhance transcriptional regulation of ATG4B and AKT1 by ATF4, which induced both autophagy and mTOR to promote cell viability.

The East China Sea Basin (ECSB) is an integral part of the Western Pacific tectonic system. Its development is linked to the Kula–Pacific Plate and the formation and expansion of the Philippine Sea Basin. Recent advancements in exploration technologies and theory have been applied to Mesozoic basins in the East China Sea. Researchers have posited that the southern basin has great oil and gas exploration potential. However, the characteristics and evolution of fault structures and their influence on hydrocarbon accumulation remain unclear. Here, in-depth geometric and kinematic analyses of Mesozoic fault structures in the southern ECSB were conducted using the latest interpretations of 2D seismic data and structural analysis theory. The findings revealed that the fault system was well developed and predominantly exhibited multiphase extensional and extensional-torsional features. Based on their lateral distribution and morphology, faults were categorized into three structural styles and seven combinations. According to their developmental timing, periods of active faulting were attributed to the Yanshan and Himalayan epochs. Multiphase fault activities strongly controlled the formation of traps and thus hydrocarbon accumulation, while earlier NE-trending faults controlled the formation of structural belts and hydrocarbon source areas.

Radar point clouds will experience variations in density, which may cause incorrect alerts during clustering. In turn, it will diminish the precision of the decision-level fusion method. To address this problem, a target detection algorithm based on fusing radar with a camera in the presence of a fluctuating signal intensity is proposed in this paper. It introduces a snow ablation optimizer (SAO) for solving the optimal parameters of the density-based spatial clustering of applications with noise (DBSCAN). Subsequently, the enhanced DBSCAN clusters radar point clouds, and the valid clusters are fused with monocular camera targets. The experimental results indicate that the suggested fusion method can attain a Balance-score ranging from 0.97 to 0.99, performing outstandingly in preventing missed detections and false alarms. Additionally, the fluctuation range of the Balance-score is within 0.02, indicating the algorithm has an excellent robustness.

Marine-derived fungi are assuming an increasingly central role in the search for natural leading compounds with unique chemical structures and diverse pharmacological properties. However, some gene clusters are not expressed under laboratory conditions. In this study, we have found that a marine-derived fungus Aspergillus sp. SYPUF29 would survive well by adding an exogenous nitric oxide donor (sodium nitroprusside, SNP) and nitric oxide synthetase inhibitor (L-NG-nitroarginine methyl ester, L-NAME) in culture conditions. Moreover, using the LC-MS/MS, we initially assessed and characterized the difference in metabolites of Aspergillus sp. SYPUF29 with or without an additional source of nitrogen. We have found that the metabolic pathway of Arginine and proline metabolism pathways was highly enriched, which was conducive to the accumulation of alkaloids and nitrogen-containing compounds after adding an additional source of nitrogen in the cultivated condition. Additionally, the in vitro anti-neuroinflammatory study showed that the extracts after SNP and L-NAME were administrated can potently inhibit LPS-induced NO-releasing of BV2 cells with lower IC50 value than without nitric oxide. Further Western blotting assays have demonstrated that the mechanism of these extracts was associated with the TLR4 signaling pathway. Additionally, the chemical investigation was conducted and led to nine compounds (SF1–SF9) from AS1; and six of them belonged to alkaloids and nitrogen-containing compounds (SF1–SF6), of which SF1, SF2, and SF8 exhibited stronger activities than the positive control, and showed potential to develop the inhibitors of neuroinflammation.

Abstract One of the main challenges in small molecule drug discovery is finding novel chemical compounds with desirable activity. Traditional drug development typically begins with target selection, but the correlation between targets and disease remains to be further investigated, and drugs designed based on targets may not always have the desired drug efficacy. The emergence of machine learning provides a powerful tool to overcome the challenge. Herein, a machine learning‐based strategy is developed for de novo generation of novel compounds with drug efficacy termed DTLS (Deep Transfer Learning‐based Strategy) by using dataset of disease‐direct‐related activity as input. DTLS is applied in two kinds of disease: colorectal cancer (CRC) and Alzheimer's disease (AD). In each case, novel compound is discovered and identified in in vitro and in vivo disease models. Their mechanism of actionis further explored. The experimental results reveal that DTLS can not only realize the generation and identification of novel compounds with drug efficacy but also has the advantage of identifying compounds by focusing on protein targets to facilitate the mechanism study. This work highlights the significant impact of machine learning on the design of novel compounds with drug efficacy, which provides a powerful new approach to drug discovery.

Cr(VI) is known to be seriously toxic and carcinogenic. Hypoxia-inducible factor-1α (HIF-1α) is a crucial regulator to promote tumor development. In this study, we found that Cr(VI) significantly increased the expression of HIF-1α in A549 cells and in lung of BALB/c mice but not in HELF cells. Treatment with Lificiguat (YC-1), HIF-1α inhibitor, or CoCl2, HIF-1α inducer, could alter Cr(VI)-induced autophagy, glycolysis, and cell growth in A549 cells but not in HELF cells, validating the involvement of HIF-1α in these effects of Cr(VI) in A549 cells. Co-treatments of pcATG4B with YC-1, or siATG4B with CoCl2 demonstrated the role of HIF-1α / autophagy axis in inducing glycolysis and cell growth in A549 cells. In HELF cells, however, only autophagy but not HIF-1α played a role in inducing glycolysis. The protein level of p53 was significantly lower in A549 cells than in HELF cells. RITA, a p53 inducer, attenuated Cr(VI)-induced HIF-1α and LC3-II in A549 cells, suggesting that p53 might be the mechanism underlying the different effects of Cr(VI) on HIF-1α in A549 and HELF cells. Thus, p53-dependent HIF-1α / autophagy-mediated glycolysis plays a role in facilitating Cr(VI)-induced carcinogenesis.

Decision-level information fusion methods using radar and vision usually suffer from low target matching success rates and imprecise multi-target detection accuracy. Therefore, a robust target detection algorithm based on the fusion of frequency-modulated continuous wave (FMCW) radar and a monocular camera is proposed to address these issues in this paper. Firstly, a lane detection algorithm is used to process the image to obtain lane information. Then, two-dimensional fast Fourier transform (2D-FFT), constant false alarm rate (CFAR), and density-based spatial clustering of applications with noise (DBSCAN) are used to process the radar data. Furthermore, the YOLOv5 algorithm is used to process the image. In addition, the lane lines are utilized to filter out the interference targets from outside lanes. Finally, multi-sensor information fusion is performed for targets in the same lane. Experiments show that the balanced score of the proposed algorithm can reach 0.98, which indicates that it has low false and missed detections. Additionally, the balanced score is almost unchanged in different environments, proving that the algorithm is robust.

BackgroundGram-negative bacteria is a global public health problem. Treatment options include novel beta-lactamase inhibitors.ObjectivesThe objective of this study was to collect information on the efficacy and safety of novel β-lactamase inhibitor combinations such as imipenem-cilastatin/relebactam (IMI/REL).MethodsIn order to comprehensively evaluate the clinical, microbiological, and adverse events outcomes, a meta-analysis was conducted on clinical trials comparing novel β-lactamase inhibitor combinations with existing comparator therapies.ResultsFour studies comprising 948 patients were included in the analysis. IMI/REL therapy demonstrated similar clinical responses to comparators across various treatment visits, including discontinuation of intravenously administered therapy visits [DCIV, RR = 1.00 (0.88, 1.12)], early follow-up visits [EFU, RR = 1.00 (0.89, 1.14)], late follow-up visits [LFU, RR = 1.00 (0.88, 1.13)]. Moreover, no significant difference in the microbiologic response of MITT patients was observed between IMI/REL and comparators across DCIV [RR = 0.99 (0.89, 1.11)], EFU [RR = 1.01 (0.95, 1.07)], and LFU visits [RR = 1.00 (90.94, 1.07)]. In terms of safety, therapy with IMI/REL and comparators exhibited similar risks of at least one adverse event (AE), drug-related AEs, and discontinuation due to AEs. The incidence of serious AEs (SAEs) was significantly lower in the IMI/REL group compared to the comparison groups. The predominant AEs were gastrointestinal disorders, with no significant difference observed between the IMI/REL group and comparators.ConclusionThe clinical and microbiologic response to IMI/REL in the treatment of bacterial infection was comparable to that of the comparator. Furthermore, the incidence of AEs and the tolerability of IMI/REL were similar among the comparators. Based on these findings, IMI/REL can be considered as a viable alternative treatment option.

Abstract Background Moso bamboo (Phyllostachys edulis) is a well-known bamboo species of high economic value in the textile industry due to its rapid growth. Phytohormones, which are master regulators of growth and development, serve as important endogenous signals. However, the mechanisms through which phytohormones regulate growth in moso bamboo remain unknown to date. Results Here, we reported that exogenous gibberellins (GA) applications resulted in a significantly increased internode length and lignin condensation. Transcriptome sequencing revealed that photosynthesis-related genes were enriched in the GA-repressed gene class, which was consistent with the decrease in leaf chlorophyll concentrations and the lower rate of photosynthesis following GA treatment. Exogenous GA applications on seedlings are relatively easy to perform, thus we used 4-week-old whole seedlings of bamboo for GA- treatment followed by high throughput sequencing. In this study, we identified 932 cis-nature antisense transcripts (cis-NATs), and 22,196 alternative splicing (AS) events in total. Among them, 42 cis-nature antisense transcripts (cis-NATs) and 442 AS events were differentially expressed upon exposure to exogenous GA3, suggesting that post-transcriptional regulation might be also involved in the GA3 response. Targets of differential expression of cis-NATs included genes involved in hormone receptor, photosynthesis and cell wall biogenesis. For example, LAC4 and its corresponding cis-NATs were GA3-induced, and may be involved in the accumulation of lignin, thus affecting cell wall composition. Conclusions This study provides novel insights illustrating how GA alters post-transcriptional regulation and will shed light on the underlying mechanism of growth modulated by GA in moso bamboo.

A large number of literatures have investigated the selective photocatalytic reaction of 4-aminothiophenol (PATP) to p,p'-dimercaptoazobenzene (DMAB). Most of them mainly study the contribution of substrate, excitation wavelength, exposure time, pH and added cations to plasmon-assisted surface catalytic reactions. However, we mainly study focuses on the effects of solvents on the dimerization of PATP to DMAB under the action of Ag nanoparticles (NPs). In experiments, a variety of diols was selected as solvents for the probe molecule PATP, and power-dependent SERS spectra were obtained at an excitation wavelength of 532 nm. From the laser-dependent SERS spectrum, we found that the characteristic peak enhancement effect of the product DMAB in different solvents is significantly different. That is, different solvents could regulate the rate at which DMAB is produced from PATP. Based on the experimental results, we further explored how different diol solvents regulate the response of PATP to DMAB. Our conclusion is that the solvent in the system can quickly capture the hot electrons generated by the decay of the plasmon, so that the remaining holes can oxidize PATP to form DMAB. The ability to trap hot electrons is different due to the difference in the position of the functional groups in the solvent, so that the photocatalytic reaction rate of the hole-oxidized PATP is different. The ability to capture electrons varies depending on the position of the functional groups in the solvent, so the oxidation rate of the photocatalytic reaction is also different. This work not only deepens our understanding of the mechanism of hole-driven surface catalysis oxidation reaction, but also provides a convenient method for regulating the rate of catalytic oxidation.

Plants have evolved diverse cell types with distinct sizes, shapes, and functions. For example, most flowering plants contain specialized petal conical epidermal cells that are thought to attract pollinators and influence light capture and reflectance, but the molecular mechanisms controlling conical cell shaping remain unclear. Here, through a genetic screen in Arabidopsis thaliana, we demonstrated that loss-of-function mutations in ANGUSTIFOLIA (AN), which encodes for a homolog of mammalian CtBP/BARs, displayed conical cells phenotype with wider tip angles, correlating with increased accumulation of reactive oxygen species (ROS). We further showed that exogenously supplied ROS generated similar conical cell phenotypes as the an mutants. Moreover, reduced endogenous ROS levels resulted in deceased tip sharpening of conical cells. Furthermore, through enhancer screening, we demonstrated that mutations in katanin (KTN1) enhanced conical cell phenotypes of the an-t1 mutants. Genetic analyses showed that AN acted in parallel with KTN1 to control conical cell shaping. Both increased or decreased ROS levels and mutations in AN suppressed microtubule organization into well-ordered circumferential arrays. We demonstrated that the AN-ROS pathway jointly functioned with KTN1 to modulate microtubule ordering, correlating with the tip sharpening of conical cells. Collectively, our findings revealed a mechanistic insight into ROS homeostasis regulation of microtubule organization and conical cell shaping.

The reagent Rh-C, incorporating a rhodamine moiety and a coumarin backbone and prepared via click chemistry, was developed as the first single molecule for detecting Cu2+, Fe3+ and Cr3+. Its response to Cu2+ in different solutions is visible to the naked eye and it exhibits a ratiometric fluorescence response to Fe3+ in methanol and Cr3+ in acetonitrile.

Cortical microtubules guide the direction and deposition of cellulose microfibrils to build the cell wall, which in turn influences cell expansion and plant morphogenesis. In the model plant Arabidopsis thaliana (Arabidopsis), petal is a relatively simple organ that contains distinct epidermal cells, such as specialized conical cells in the adaxial epidermis and relatively flat cells with several lobes in the abaxial epidermis. In the past two decades, the Arabidopsis petal has become a model experimental system for studying cell expansion and organ morphogenesis, because petals are dispensable for plant growth and reproduction. Recent advances have expanded the role of microtubule organization in modulating petal anisotropic shape formation and conical cell shaping during petal morphogenesis. Here, we summarize recent studies showing that in Arabidopsis, several genes, such as SPIKE1, Rho of plant (ROP) GTPases, and IPGA1, play critical roles in microtubule organization and cell expansion in the abaxial epidermis during petal morphogenesis. Moreover, we summarize the live-confocal imaging studies of Arabidopsis conical cells in the adaxial epidermis, which have emerged as a new cellular model. We discuss the microtubule organization pattern during conical cell shaping. Finally, we propose future directions regarding the study of petal morphogenesis and conical cell shaping.

Background: Hypertrophy of the ligamentum flavum (HLF) is a common contributor to spinal stenosis which results in significant neurological impairments. Circular RNA (circRNA) circ_0003609 has been linked to HLF; however, the exact mechanism by which it causes this disease is unclear. Methods: Circ_0003609 expressions were regulated in HLF cells by overexpression vectors and RNA interference. Cell proliferation and fibrosis-related gene expression were checked by the Cell Counting Kit-8 (CCK-8) assay and western blotting. CircBank's prediction of the association between miR-155 and circ_0003609 was supported by a dual-luciferase reporter experiment. The function of the miR-155/sirtuin 1 (SIRT1) axis in controlling HLF fibrosis was further examined. Results: Overexpression of circ_0003609 suppressed HLF cell propagation and fibrosis compared to its silencing. It was found that circ_0003609 served as the sponge for miR-155 and that the circ_0003609/miR-155 axis controlled the fibrosis of HLF cells. It was found that circ_0003609 acted as a sponge for miR-155, regulating the fibrosis of HLF cells. Further, miR-155 targets SIRT1, and the miR-155/SIRT1 axis promotes HLF cell fibrosis. Conclusion: Circ_0003609 ameliorates hypertrophied ligamentum flavum (LF) by modulating the miR-155/SIRT1 axis, indicating a potential treatment approach for HLF. [ABSTRACT FROM AUTHOR]

The thermodynamic parameters of the complexes of Th with N-methylethylenediamine-N,N',N'-triacetic acid (MEDTA; denoted as H3L with three dissociable protons) were studied. Potentiometry and microcalorimetry were used to determine formation constants and enthalpies, respectively. Thermodynamic analysis revealed two successively formed complexes, namely, ThL+ and ThL22-(L3-denotes the totally deprotonated MEDTA). Results indicated that both complexation reactions were exothermic and driven by entropic force. The first stepwise reaction (Th4+ + L3- = ThL+) was mainly driven by entropy with minimal effect on enthalpy change. The second stepwise reaction (ThL+ + L3- = ThL22-) was more exothermic and showed less entropic change than the first stepwise reaction. The strong chelation of MEDTA would inhibit the hydrolysis of Th4+ and increase solubility. [ABSTRACT FROM AUTHOR]