pH-responsive hierarchical H2S-releasing nano-disinfectant with deep-penetrating and anti-inflammatory properties for synergistically enhanced eradication of bacterial biofilms and wound infection.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) biofilm-associated bacterial infection is the primary cause of nosocomial infection and has long been an ongoing threat to public health. MRSA biofilms are often resistant to multiple antimicrobial strategies, mainly due to the existence of a compact protective barrier; thus, protecting themselves from the innate immune system and antibiotic treatment via limited drug penetration. RESULTS: A hierarchically structured hydrogen sulfide (H2S)-releasing nano-disinfectant was presented, which was composed of a zinc sulfide (ZnS) core as a H2S generator and indocyanine green (ICG) as a photosensitizer. This nano-disinfectant (ICG-ZnS NPs) sensitively responded to the biofilm microenvironment and demonstrated efficient eradication of MRSA biofilms via a synergistic effect of Zn2+, gas molecule-mediated therapy, and hyperthermia. Physically boosted by released H2S and a near-infrared spectroscopy-induced hyperthermia effect, ICG-ZnS NPs destroyed the compactness of MRSA biofilms showing remarkable deep-penetration capability. Moreover, on-site generation of H2S gas adequately ameliorated excessive inflammation, suppressed secretion of inflammatory cytokines, and expedited angiogenesis, therefore markedly accelerating the in vivo healing process of cutaneous wounds infected with MRSA biofilms. CONCLUSION: ICG-ZnS NPs combined with NIR laser irradiation exhibited significant anti-biofilm activity in MRSA biofilms, can accelerate the healing process through deep-penetration and anti-inflammatory effectuation. The proposed strategy has great potential as an alternative to antibiotic treatment when combating multidrug-resistant bacterial biofilms.

ULM-MbCNRT: In vivo Ultrafast Ultrasound Localization Microscopy by Combining Multi-branch CNN and Recursive Transformer.

Ultrasound localization microscopy (ULM) overcomes the acoustic diffraction limit by localizing tiny microbubbles (MBs), thus enabling the microvascular to be rendered at sub-wavelength resolution. Nevertheless, to obtain such superior spatial resolution, it is necessary to spend tens of seconds gathering numerous ultrasound (US) frames to accumulate MB events required, resulting in ULM imaging still suffering from trade-offs between imaging quality, data acquisition time and data processing speed. In this paper, we present a new deep learning (DL) framework combining multi-branch CNN and recursive Transformer, termed as ULM-MbCNRT, that is capable of reconstructing a super-resolution image directly from a temporal mean low-resolution image generated by averaging much fewer raw US frames, i.e., implement an ultrafast ULM imaging. To evaluate the performance of ULM-MbCNRT, a series of numerical simulations and in vivo experiments are carried out. Numerical simulation results indicate that ULM-MbCNRT achieves high-quality ULM imaging with ~10-fold reduction in data acquisition time and ~130-fold reduction in computation time compared to the previous DL method (e.g., the modified sub-pixel convolutional neural network, ULM-mSPCN). For the in vivo experiments, when comparing to the ULM-mSPCN, ULM-MbCNRT allows ~37-fold reduction in data acquisition time (~0.8 s) and ~2134-fold reduction in computation time (~0.87 s) without sacrificing spatial resolution. It implies that ultrafast ULM imaging holds promise for observing rapid biological activity in vivo, potentially improving the diagnosis and monitoring of clinical conditions.

Reconstructing Cancellous Bone From Down-Sampled Optical-Resolution Photoacoustic Microscopy Images With Deep Learning.

OBJECTIVE: Bone diseases deteriorate the microstructure of bone tissue. Optical-resolution photoacoustic microscopy (OR-PAM) enables high spatial resolution of imaging bone tissues. However, the spatiotemporal trade-off limits the application of OR-PAM. The purpose of this study was to improve the quality of OR-PAM images without sacrificing temporal resolution. METHODS: In this study, we proposed the Photoacoustic Dense Attention U-Net (PADA U-Net) model, which was used for reconstructing full-scanning images from under-sampled images. Thereby, this approach breaks the trade-off between imaging speed and spatial resolution. RESULTS: The proposed method was validated on resolution test targets and bovine cancellous bone samples to demonstrate the capability of PADA U-Net in recovering full-scanning images from under-sampled OR-PAM images. With a down-sampling ratio of [4, 1], compared to bilinear interpolation, the Peak Signal-to-Noise Ratio and Structural Similarity Index Measure values (averaged over the test set of bovine cancellous bone) of the PADA U-Net were improved by 2.325 dB and 0.117, respectively. CONCLUSION: The results demonstrate that the PADA U-Net model reconstructed the OR-PAM images well with different levels of sparsity. Our proposed method can further facilitate early diagnosis and treatment of bone diseases using OR-PAM.

Strategies to Regulate the Degradation and Clearance of Mesoporous Silica Nanoparticles: A Review.

Mesoporous silica nanoparticles (MSNs) have attracted extensive attention as drug delivery systems because of their unique meso-structural features (high specific surface area, large pore volume, and tunable pore structure), easily modified surface, high drug-loading capacity, and sustained-release profiles. However, the enduring and non-specific enrichment of MSNs in healthy tissues may lead to toxicity due to their slow degradability and hinder their clinical application. The emergence of degradable MSNs provided a solution to this problem. The understanding of strategies to regulate degradation and clearance of these MSNs for promoting clinical trials and expanding their biological applications is essential. Here, a diverse variety of degradable MSNs regarding considerations of physiochemical properties and doping strategies of degradation, the biodistribution of MSNs in vivo, internal clearance mechanism, and adjusting physical parameters of clearance are highlighted. Finally, an overview of these degradable and clearable MSNs strategies for biosafety is provided along with an outlook of the encountered challenges.

Ultrafast Ultrasound Localization Microscopy by Conditional Generative Adversarial Network.

Ultrasound localization microscopy (ULM) overcomes the acoustic diffraction limit and enables the visualization of microvasculature at subwavelength resolution. However, challenges remain in ultrafast ULM implementation, where short data acquisition time, efficient data processing speed, and high imaging resolution need to be considered simultaneously. Recently, deep learning (DL)-based methods have exhibited potential in speeding up ULM imaging. Nevertheless, a certain number of ultrasound (US) data ( L frames) are still required to accumulate enough localized microbubble (MB) events, leading to an acquisition time within a time span of tens of seconds. To further speed up ULM imaging, in this article, we present a new DL-based method, termed as ULM-GAN. By using a modified conditional generative adversarial network (cGAN) framework, ULM-GAN is able to reconstruct a superresolution image directly from a temporal mean low-resolution (LR) image generated by averaging l -frame raw US images with l being significantly smaller than L . To evaluate the performance of ULM-GAN, a series of numerical simulations and phantom experiments are both implemented. The results of the numerical simulations demonstrate that when performing ULM imaging, ULM-GAN allows  âˆ¼ 40 -fold reduction in data acquisition time and  âˆ¼ 61 -fold reduction in computational time compared with the conventional Gaussian fitting method, without compromising spatial resolution according to the resolution scaled error (RSE). For the phantom experiments, ULM-GAN offers an implementation of ULM with ultrafast data acquisition time (  âˆ¼ 0.33 s) and ultrafast data processing speed (  âˆ¼ 0.60 s) that makes it promising to observe rapid biological activities in vivo.

Investigation of Asian Dyes and Pigments from the Artifact of "Murongzhi" and the Silk Road in China.

In this paper, a series of modern analysis methods, including Raman spectroscopy, X-ray diffraction, UV-vis spectrophotometry, and ultra-high-pressure liquid chromatography coupled with a thermoelectric LTQ-Orbitrap XL ETD mass spectrometer (UHPLC-MS/MS), were applied to analyze and accurately identify the chemical composition of plant dyes and the mineral pigment from the samples collected from grave goods. As a result, the textiles were dyed by the madder, Kermes, Phellodendron chinense, indigo, Lithospermum L., and so forth. In addition, the mineral pigment, charcoal, hematite, minium, cinnabar, azurite, and malachite were used to paint the exquisite artifacts in the tomb of Murongzhi. This research demonstrates the profound impact on cultural transmission and fusion in the "Tuyuhong" dynasty and explores the Silk Road in Tang dynasty.

Rapid screening of antioxidant from natural products by AAPH-Incubating HPLC-DAD-HR MS/MS method: A case study of Gardenia jasminoides fruit.

A new AAPH-Incubating HPLC-DAD-HR MS/MS method was developed for the rapid and high-throughput screening of antioxidants directly in natural products and applied to Gardenia jasminoides fruit. This method was assumed that the peak areas of compounds with potential antioxidant activity in HPLC chromatograms would be significantly reduced or disappeared after incubating with the AAPH which can release ROO at physiological conditions (37 °C, pH 7.4). Additionally, the activity of antioxidants can be evaluated by comparing the peak reduction rates and the screened components can be further identified by HRMS/MS. Then, 17 potential natural antioxidants from the crude extract of GJF was screened. Among them, three major components including crocin I, crocin II and crocetin showed excellent ROO scavenging activity, which were further validated by the ORAC assay. In conclusion, our study provided a simple and effective strategy to rapidly screen antioxidants in natural products.

Recent Advances in Mesoporous Silica Nanoparticles Delivering siRNA for Cancer Treatment.

Silencing genes using small interfering (si) RNA is a promising strategy for treating cancer. However, the curative effect of siRNA is severely constrained by low serum stability and cell membrane permeability. Therefore, improving the delivery efficiency of siRNA for cancer treatment is a research hotspot. Recently, mesoporous silica nanoparticles (MSNs) have emerged as bright delivery vehicles for nucleic acid drugs. A comprehensive understanding of the design of MSN-based vectors is crucial for the application of siRNA in cancer therapy. We discuss several surface-functionalized MSNs' advancements as effective siRNA delivery vehicles in this paper. The advantages of using MSNs for siRNA loading regarding considerations of different shapes, various options for surface functionalization, and customizable pore sizes are highlighted. We discuss the recent investigations into strategies that efficiently improve cellular uptake, facilitate endosomal escape, and promote cargo dissociation from the MSNs for enhanced intracellular siRNA delivery. Also, particular attention was paid to the exciting progress made by combining RNAi with other therapies to improve cancer therapeutic outcomes.

Polyacrylic Acid-Functionalized Graphene@Ca(OH)2 Nanocomposites for Mural Protection.

Murals are one of the precious legacies of our ancestors; however, they face severe damage along with archeological discoveries, which need urgent repair. Nowadays, nanotechnology provides new concepts and materials for the consolidation and protection of murals. In this work, an innovative method for the protection of murals was proposed with graphene-based nanomaterials through strategically synthesizing a polyacrylic acid-functionalized graphene/nano-Ca(OH)2 material (PAAG@Ca(OH)2) by a facile and economic aqueous method. As a result, the nanocomposite PAAG@Ca(OH)2 was demonstrated with high porosity, strong adsorption, appropriate hydrophilicity, and better permeability compared to the commercial AC33 sample according to the simulated tests. As expected, the nanocomposite PAAG@Ca(OH)2 displayed a promising application for the reinforcement of murals, which opens up a new avenue for the protection of murals.

Protective effects of Huang-Lian-Jie-Du Decoction on diabetic nephropathy through regulating AGEs/RAGE/Akt/Nrf2 pathway and metabolic profiling in db/db mice.

BACKGROUND: Diabetic nephropathy (DN) is a severe diabetic complication that is the principal cause of end-stage kidney disease worldwide. Huang-Lian-Jie-Du Decoction (HLJDD) is widely used to treat diabetes clinically. However, the nephroprotective effects and potential mechanism of action of HLJDD against DN have not yet been fully elucidated. PURPOSE: This study aimed to investigate the potential roles of HLJDD in DN and elucidate its mechanisms in db/db mice. METHODS: An integrated strategy of network pharmacology, pharmacodynamics, molecular biology, and metabolomics was used to reveal the mechanisms of HLJDD in the treatment of DN. First, network pharmacology was utilized to predict the possible pathways for DN using the absorbed ingredients of HLJDD in rat plasma in silico. Then, combined with histopathological examination, biochemical evaluation immunohistochemistry/immunofluorescence assay, western blot analysis, and UPLC-Q-Orbitrap HRMS/MS-based metabolomics approach were applied to evaluate the efficacy of HLJDD against DN and its underlying mechanisms in vivo. RESULTS: In silico, network pharmacology indicated that the AGEs/RAGE pathway was the most prominent pathway for HLJDD against DN. In vivo, HLJDD exerted protective effects against DN by ameliorating glycolipid metabolic disorders and kidney injury. Furthermore, we verified that HLJDD protected against DN by regulating the AGEs/RAGE/Akt/Nrf2 pathway for the first time. In addition, 22 potential biomarkers were identified in urine, including phenylalanine metabolism, tryptophan metabolism, glucose metabolism, and sphingolipid metabolism. CONCLUSION: These findings suggest that HLJDD ameliorates DN by regulating the AGEs/RAGE/Akt/Nrf2 pathway and metabolic profiling.

Non-targeted metabolomic analysis of variation of volatile fractions of ginseng from different habitats by HS-SPME-GC-MS coupled with chemometrics.

Cultivated ginseng (CG), transplanted ginseng (TG) and mountain cultivated ginseng (MCG) classified by the habitat type all belong to Panax ginseng and were reported to have similar types of secondary metabolites. Nonetheless, owing to the distinctly diverse habitats in which these ginseng types grow, their pharmacological effects differ. In the present study, an emerging analytical approach involving headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) was established to effectively distinguish among CG, TG and MCG. First, the volatile components were analysed and identified by using the NIST library combined with measured retention indices (Kovats', RI), and a total of 78 volatile components were finally characterized, which included terpenes, alcohols, esters, aldehydes and alkynols. Furthermore, multivariate statistical approaches, principal component analysis (PCA) and orthogonal partial least-squares discrimination analysis (OPLS-DA) were subsequently utilized to screen for compounds of significance. Under optimized HS-SPME-GC-MS conditions, 12, 16, and 16 differential markers were screened in the CG-TG, CG-MCG and TG-MCG groups, respectively. Our study suggested that HS-SPME-GC-MS analysis combined with metabolomic analytical methods and chemometric techniques can be applied as potent tools to identify chemical marker candidates to distinguish CG, TG and MCG.

Hyaluronic acid-based supramolecular medicine with polyamines sequestration capability for cooperative anti-psoriasis.

Psoriasis seriously harms physical and mental health of patients. Hyaluronic acid (HA)-based topical formulation can increase drug concentration in psoriatic skin via CD44-assisted targeting. Herein, we developed a supramolecular medicine composed of curcumin-loaded HA-cucurbit[7]uril (HA-CB[7]@Cur), which could efficiently sequester polyamines (PAs) via host-guest interactions of CB[7] and PAs to suppress RNA-PAs immunocomplex formation. Meanwhile, anti-psoriasis drug Cur could be released from HA-CB[7]@Cur by PAs. With phenotypical disease evaluation, psoriasis area measurements and severity index scoring, and histological characterizations, we demonstrate topical administration of Carbopol gel formulation of HA-CB[7]@Cur on psoriasis-like skin in mice exhibited an enhanced anti-psoriasis activity, in comparison with gel of free Cur or HA-CB[7]. Cytokine expression analysis in psoriatic skin also supported the observed therapeutic outcomes. We provide a novel and effective supramolecular strategy to realize cooperative anti-psoriasis via controlled release of curcumin and PAs sequestration, which can be potentially expanded to treat other PA-involved skin inflammatory diseases.

Artifact removal in photoacoustic tomography with an unsupervised method.

Photoacoustic tomography (PAT) is an emerging biomedical imaging technology that can realize high contrast imaging with a penetration depth of the acoustic. Recently, deep learning (DL) methods have also been successfully applied to PAT for improving the image reconstruction quality. However, the current DL-based PAT methods are implemented by the supervised learning strategy, and the imaging performance is dependent on the available ground-truth data. To overcome the limitation, this work introduces a new image domain transformation method based on cyclic generative adversarial network (CycleGAN), termed as PA-GAN, which is used to remove artifacts in PAT images caused by the use of the limited-view measurement data in an unsupervised learning way. A series of data from phantom and in vivo experiments are used to evaluate the performance of the proposed PA-GAN. The experimental results show that PA-GAN provides a good performance in removing artifacts existing in photoacoustic tomographic images. In particular, when dealing with extremely sparse measurement data (e.g., 8 projections in circle phantom experiments), higher imaging performance is achieved by the proposed unsupervised PA-GAN, with an improvement of ∼14% in structural similarity (SSIM) and ∼66% in peak signal to noise ratio (PSNR), compared with the supervised-learning U-Net method. With an increasing number of projections (e.g., 128 projections), U-Net, especially FD U-Net, shows a slight improvement in artifact removal capability, in terms of SSIM and PSNR. Furthermore, the computational time obtained by PA-GAN and U-Net is similar (∼60 ms/frame), once the network is trained. More importantly, PA-GAN is more flexible than U-Net that allows the model to be effectively trained with unpaired data. As a result, PA-GAN makes it possible to implement PAT with higher flexibility without compromising imaging performance.

Rapid screening of neuroprotective components from Huang-Lian-Jie-Du Decoction by living cell biospecific extraction coupled with HPLC-Q-Orbitrap-HRMS/MS analysis.

Huang-Lian-Jie-Du Decoction (HLJDD), a well-known traditional Chinese formulation, has been proved to exert neuroprotective effects, however, the bioactive components in HLJDD still remain to be elucidated. In the present study, a rapid and effective method involving live cell biospecific extraction and HPLC-Q-Orbitrap HRMS/MS was utilized to rapidly screen and identify the neuroprotective compounds from the HLJDD crude extract directly. Firstly, sixteen principal components in HLJDD crude extract were identified by HPLC-Q-Orbitrap HRMS/MS analysis. After co-incubation with PC12 cells, which have been validated as the key target cells for neurodegenerative diseases, seven compounds of them were demonstrated to exhibit binding affinity to the target cells. Furthermore, three representative compounds named baicalin, wogonoside, and berberine were subsequently verified to exert cytoprotective effects on PC12 cells injured by hydrogen peroxide via inhibiting oxidative stress and cell apoptosis, indicating that these screened compounds may possess a potential for the treatment of neurodegenerative diseases and were responsible, in part at least, for the neuroprotective beneficial effects of HLJDD. Taken together, our study provides evidence that live cell biospecific extraction coupled with LC-HRMS/MS technique is an efficient method for rapid screening potential bioactive components in traditional Chinese medicines.

Pterostilbene prevents methylglyoxal-induced cytotoxicity in endothelial cells by regulating glyoxalase, oxidative stress and apoptosis.

Methylglyoxal (MGO), a cytotoxic byproduct of glycolysis in biological systems, can induce endothelial cells dysfunction, implicated in diabetic vascular complications. Pterostilbene (PTS), a naturally occurring resveratrol derivative, is involved in various pharmacological activities. This study aimed to explore the effects of PTS on MGO induced cytotoxicity in human umbilical vein endothelial cells (HUVECs) and the underlying mechanisms for the first time. In the current study, it has been demonstrated that PTS could enhance the level of glyoxalase 1 (GLO-1) and elevate glutathione (GSH) content to active the glyoxalase system, resulting in elimination of the toxic MGO as well as advanced glycation end products (AGEs) in HUVECs. Meanwhile, PTS could also suppress oxidative stress and thus exert cytoprotective effects by elevating Nrf2 nuclear translocation and the corresponding down-stream antioxidant enzymes in MGO induced HUVECs. In addition, PTS could alleviate MGO induced apoptosis in HUVECs via inhibition of oxidative stress and associated downstream mitochondria-dependent signaling apoptotic cascades, as characterized by preventing caspases family activation. Taken together, these findings suggest that PTS could protect against MGO induced endothelial cell cytotoxicity by regulating glyoxalase, oxidative stress and apoptosis, suggesting that PTS could be beneficial in the treatment of diabetic vascular complications.

A Sterically Congested Nitrogenated Benzodipentaphene with a Double π-Expanded Helicene Structure.

Herein, we describe a series of three sterically congested nitrogenated benzodipentaphenes, one of which shows a highly distorted aromatic backbone with an unprecedented double π-expanded helicene structure.

Electrochemical CO2 reduction by a cobalt bipyricorrole complex: decrease of an overpotential value derived from monoanionic ligand character of the porphyrinoid species.

A newly synthesized Co(ii) complex with a monoanionic bipyricorrole ligand is found to catalytically promote a selective CO2 electroreduction to CO with Faradaic efficiency of 75%. Catalytic Tafel plots show that the overpotential of Co(ii) bipyricorrole is 0.35 V lower than that of a Co(ii) complex with the dianionic tetraphenylporphyrin ligand.

The Solanum lycopersicum auxin response factor SlARF2 participates in regulating lateral root formation and flower organ senescence.

ARF2 as apleiotropic developmental regulator has been reported in Arabidopsis thaliana and tomato (Solanum lycopersicum). The present study showed SlARF2 transcripts in all tomato plant tissues but with higher accumulation in flowers. During bud-anthesis stages, SlARF2 transcripts showed a dynamic expression pattern in sepal, stamen, ovary and petal. Hormone treatment analysis suggested that SlARF2 transcript accumulation was positively regulated by auxin and gibberellic acid, and negatively regulated by ethylene in tomato seedlings. Phenotypes and molecular analyses of SlARF2-upregulated transgenic tomato indicated that SlARF2 regulated tomato lateral root formation and flower organ senescence may be partially mediated by regulating the gene expression of auxin and ethylene response factors. The data enlarges the functional characterization of SlARF2 in tomato, and broadens our understanding of auxin signaling in regulating plant growth and development.