Imaging-Guided Biomimetic M1 Macrophage Membrane-Camouflaged Magnetic Nanorobots for Photothermal Immunotargeting Cancer Therapy.

Biohybrid micro/nanorobots have demonstrated improved therapeutic outcomes for targeting and treating diseases in preclinical trials. However, in vivo applications remain challenging due to a lack of sufficient targeting. Based on evidence that immune cells play a role in the immune modulation in the tumor microenvironment, we developed M1 macrophage membrane-coated magnetic photothermal nanocomplexes (MPN) for photoacoustic (PA) imaging-guided tumor therapy. The MPN were able to inherit the protein from the original macrophage cells and exert a targeted immunosuppression role. Integrating black phosphorus quantum dots and DOX also greatly enhanced reactive oxygen species generation and chemo-phototherapy efficacy. The results suggest that the MPN can be employed as an excellent tumor immunotargeting nanorobotic platform for modulating the tumor microenvironment under PA imaging and magnetic guidance and, thus, exert synergistic therapeutic efficacies.

Transcriptome analysis reveals multiple effects of nitrogen accumulation and metabolism in the roots, shoots, and leaves of potato (Solanum tuberosum L.).

BACKGROUND: Nitrogen (N) is a major element and fundamental constituent of grain yield. N fertilizer plays an essential role in the roots, shoots, and leaves of crop plants. Here, we obtained two N-sensitive potato cultivars. RESULTS: The plants were cultivated in the pots using N-deficient and N-sufficient conditions. Crop height, leaf chlorophyll content, dry matter, and N-accumulation significantly decreased under N-deficient conditions. Furthermore, we performed a comprehensive analysis of the phenotype and transcriptome, GO terms, and KEGG pathways. We used WGCNA of co-expressed genes, and 116 differentially expressed hub genes involved in photosynthesis, nitrogen metabolism, and secondary metabolites to generate 23 modules. Among those modules, six NRT gene families, four pigment genes, two auxin-related genes, and two energy-related genes were selected for qRT-PCR validation. CONCLUSIONS: Overall, our study demonstrates the co-expressed genes and potential pathways associated with N transport and accumulation in potato cultivars' roots, shoots, and leaves under N-deficient conditions. Therefore, this study provides new ideas to conduct further research on improving nitrogen use efficiency in potatoes.

Side-Chain-Tuned Molecular Packing Allows Concurrently Boosted Photoacoustic Imaging and NIR-II Fluorescence.

It is generally considered that photoacoustic imaging (PAI) and fluorescence imaging (FLI) cannot be enhanced concurrently, as they are dependent on competitive photophysical processes at the single-molecule level. Herein, we reveal that BDTR9-OC8 and BDTR9-C8, which have identical π-conjugated backbones but are substituted by side chains of different rigidity, show distinct phototheranostic properties in the aggregated state. The NIR-II FLI and PAI brightness of BDTR9-C8 nanoparticles are enhanced by 4.6 and 1.4 times compared with BDTR9-OC8 nanoparticles. Theoretical calculations and GIWAXS analysis revealed that BDTR9-C8 with rigid side chains shows a relative amorphous condensed state, which will benefit the efficient transportation of photo-generated excitons and phonons, subsequently enhancing the FLI and PAI signals. Besides, both nanoparticles exhibit excellent photothermal conversion efficiency due to their strong light-harvesting capability and are considered effective photothermal therapy materials. This work provides an illuminating strategy for material design in the future.

Exploring the Potential Mechanism of Shennao Fuyuan Tang for Ischemic Stroke Based on Network Pharmacology and Molecular Docking.

METHODS: Screen the biologically active components and potential targets of SNFYT through Traditional Chinese Medicine Systems Pharmacology (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID), and related literature. In addition, DrugBank, OMIM, DisGeNET, and the Therapeutic Target Database were searched to explore the therapeutic targets of IS. The cross-targets of SNFYT potential targets and IS treatment targets were taken as candidate gene targets, and GO and KEGG enrichment analyses were performed on the candidate targets. On this basis, the SNFYT-component-target network and protein-protein interaction (PPI) network were constructed using Cytoscape 3.7.2. Finally, AutoDock was used to verify the molecular docking of core components and core targets. RESULTS: We screened out 95 potentially active components and 143 candidate targets. SNFYT-component-target network, PPI network, and Cytoscape analysis identified four core active ingredients and 14 core targets. GO enrichment analyzed 2333 biological processes, 79 cell components, and 149 molecular functions. There are 170 KEGG-related signal pathways (P < 0.05), including the IL-17 signal pathway, TNF signal pathway, and HIF-1 signal pathway. The molecular docking results of the core components and the core targets showed good binding power. CONCLUSIONS: SNFYT may achieve the effect of treating ischemic stroke through its anti-inflammatory effect through a signal pathway with core targets as the core.

[Visualization analysis of traditional Chinese medicine for neurogenesis research based on CiteSpace].

To analyze the research hotspots and trends of traditional Chinese medicine(TCM) for neurogenesis with use of CiteSpace 5.7.R3 software. The bibliometrics analysis on the literatures of TCM for neurogenesis from 1987 to 2020 included in the CNKI database was conducted to visualize the number of papers, authors, institutions and keywords. Totally 736 literatures were included and the volume of annual publications showed an upward in volatility. At present, several stable research teams have been formed, which were represented by DING Fei, ZHOU Chong-jian and ZHOU Yong-hong, but the cooperation was not close among the teams. According to the analysis of research institutions, Institute of Diagnostics of Hunan University of Chinese Medicine and Acupuncture Research Center of Tianjin University of Traditional Chinese Medicine produced largest number of literatures. The cooperation among institutions, with universities of TCM and affiliated hospitals as the main research force, was characterized by dominant cooperation among regional institutions and less cross-regional cooperation. Keywords analysis showed that in the field of TCM for neurogenesis, a lot of studies mainly focused on the disease field, treatment and medication, TCM therapy and molecular mechanism. The research on TCM therapy and molecular mechanism for neurogenesis of central nervous system will be the research hotspots in future.

Infection microenvironment-activated nanoparticles for NIR-II photoacoustic imaging-guided photothermal/chemodynamic synergistic anti-infective therapy.

Subcutaneous abscesses caused by drug-resistant bacteria pose huge challenges to human health. The design of infection microenvironment-activated biomaterials has an advantage for the diagnosis and treatment of infective diseases due to its high specificity and efficiency. Herein, a novel theranostic platform based on Cu2O nanoparticles (NPs) is successfully constructed via a simple, fast and low-cost approach. The Cu2O NPs exhibit high sensitivity to overexpressed H2S and H2O2 in the bacterial infection microenvironment. After in situ injection, the Cu2O NPs will rapidly react with the endogenous H2S to generate Cu9S8 NPs, which exhibits high absorbance in the second near-infrared (NIR-II) biowindow. The Cu9S8 NPs serving as NIR-II photoacoustic contrast agents can exactly distinguish between inflammatory and normal tissues. With the guidance of NIR-II photoacoustic imaging (PAI), H2S-activated photothermal antibacterial therapy (PTAT) can realize excellent antibacterial performance under 1060 nm laser irradiation. Meanwhile, the Cu2O NPs can effectively catalyze H2O2 at the site of inflammation to produce hydroxyl radicals with strong antibacterial property via Fenton-like reaction, resulting in the damage of bacterial cell membrane. Furthermore, the application of Cu2O NPs can enhance epidermic migration and facilitate the re-epithelialization of the infected skin. In vivo experiment shows that 97.9% methicillin-resistant Staphylococcus aureus are eliminated by the synergistic PTAT and chemodynamic antibacterial therapy.

Beyond the Liver: Liver-Eye Communication in Clinical and Experimental Aspects.

The communication between organs participates in the regulation of body homeostasis under physiological conditions and the progression and adaptation of diseases under pathological conditions. The communication between the liver and the eyes has been received more and more attention. In this review, we summarized some molecular mediators that can reflect the relationship between the liver and the eye, and then extended the metabolic relationship between the liver and the eye. We also summarized some typical diseases and phenotypes that have been able to reflect the liver-eye connection in the clinic, especially non-alcoholic fatty liver disease (NAFLD) and diabetic retinopathy (DR). The close connection between the liver and the eye is reflected through multiple pathways such as metabolism, oxidative stress, and inflammation. In addition, we presented the connection between the liver and the eye in traditional Chinese medicine, and introduced the fact that artificial intelligence may use the close connection between the liver and the eye to help us solve some practical clinical problems. Paying attention to liver-eye communication will help us have a deeper and more comprehensive understanding of certain communication between liver diseases and eyes, and provide new ideas for their potential therapeutic strategy.

Visualization analysis of traditional Chinese medicine for neurogenesis research based on CiteSpace / 中国中药杂志

To analyze the research hotspots and trends of traditional Chinese medicine(TCM) for neurogenesis with use of CiteSpace 5.7.R3 software. The bibliometrics analysis on the literatures of TCM for neurogenesis from 1987 to 2020 included in the CNKI database was conducted to visualize the number of papers, authors, institutions and keywords. Totally 736 literatures were included and the volume of annual publications showed an upward in volatility. At present, several stable research teams have been formed, which were represented by DING Fei, ZHOU Chong-jian and ZHOU Yong-hong, but the cooperation was not close among the teams. According to the analysis of research institutions, Institute of Diagnostics of Hunan University of Chinese Medicine and Acupuncture Research Center of Tianjin University of Traditional Chinese Medicine produced largest number of literatures. The cooperation among institutions, with universities of TCM and affiliated hospitals as the main research force, was characterized by dominant cooperation among regional institutions and less cross-regional cooperation. Keywords analysis showed that in the field of TCM for neurogenesis, a lot of studies mainly focused on the disease field, treatment and medication, TCM therapy and molecular mechanism. The research on TCM therapy and molecular mechanism for neurogenesis of central nervous system will be the research hotspots in future.

An All-Round Athlete on the Track of Phototheranostics: Subtly Regulating the Balance between Radiative and Nonradiative Decays for Multimodal Imaging-Guided Synergistic Therapy.

Aiming to achieve versatile phototheranostics with the integrated functionalities of multiple diagnostic imaging and synergistic therapy, the optimum use of dissipated energy through both radiative and nonradiative pathways is definitely appealing, yet a significantly challenging task. To the best of the knowledge, there have been no previous reports on a single molecular species effective at affording all phototheranostic modalities including fluorescence imaging (FLI), photoacoustic imaging (PAI), photothermal imaging (PTI), photodynamic therapy (PDT), and photothermal therapy (PTT). Herein, a simple and highly powerful one-for-all phototheranostics based on aggregation-induced emission (AIE)-active fluorophores is tactfully designed and constructed. Thanks to its strong electron donor-acceptor interaction and finely modulated intramolecular motion, the AIE fluorophore-based nanoparticles simultaneously exhibit bright near-infrared II (NIR-II) fluorescence emission, efficient reactive oxygen species generation, and high photothermal conversion efficiency upon NIR irradiation, indicating the actualization of a balance between radiative and nonradiative energy dissipations. Furthermore, the unprecedented performance on NIR-II FLI-PAI-PTI trimodal-imaging-guided PDT-PTT synergistic therapy is demonstrated by the precise tumor diagnosis and complete tumor elimination outcomes. This study thus brings a new insight into the development of superior versatile phototheranostics for practical cancer theranostics.

Protein-Bound Anthocyanin Compounds of Purple Sweet Potato Ameliorate Hyperglycemia by Regulating Hepatic Glucose Metabolism in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.

Purple sweet potato is known as a rich source of protein and anthocyanins. Anthocyanins can form complexes with protein present in food products through non-covalent forces or covalent bonds during processing, transportation, and storage as their protein affinity. We evaluated the hypoglycemic effects of protein-bound anthocyanin compounds of purple sweet potato (p-BAC-PSP) and free anthocyanin compounds of purple sweet potato (FAC-PSP) in high-fat diet/streptozotocin-induced diabetic mice. The results showed that administration of both p-BAC-PSP and FAC-PSP improved diabetic condition, as evidenced by the improvement of glucose tolerance and lipid metabolism, and the decrease of oxidative stress and liver damage. For the mechanism study, we have found that p-BAC-PSP and FAC-PSP induced the expression of AMP-activated protein kinase in liver. With p-BAC-PSP or FAC-PSP treatment, glucose transporter type 2, the protein levels of glucokinase, and insulin receptor α were found to be improved significantly (p < 0.05). Glycolysis key genes, phosphofructokinase and pyruvate kinase, were upregulated in two treatment groups, while gluconeogenic genes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, were downregulated. Our findings suggested that p-BAC-PSP has great potential as a dietary supplement with hypoglycemic activity for general, pre-diabetic, and diabetic population.

Mo2 C-Derived Polyoxometalate for NIR-II Photoacoustic Imaging-Guided Chemodynamic/Photothermal Synergistic Therapy.

To overcome the current limitations of chemodynamic therapy (CDT), a Mo2 C-derived polyoxometalate (POM) is readily synthesized as a new CDT agent. It permits synergistic chemodynamic and photothermal therapy operating in the second near-infrared (NIR-II) biological transparent window for deep tissue penetration. POM aggregated in an acidic tumor micro-environment (TME) whereby enables specific tumor targeting. In addition to the strong ability to produce singlet oxygen (1 O2 ) presumably via Russell mechanism, its excellent photothermal conversion enhances the CDT effect, offers additional tumor ablation modality, and permits NIR-II photoacoustic imaging. Benefitting from the reversible redox property of molybdenum, the theranostics based on POM can escape from the antioxidant defense system. Moreover, combining the specific responsiveness to TME and localized laser irradiation, side-effects shall be largely avoided.

Sodium butyrate supplementation ameliorates diabetic inflammation in db/db mice.

Endotoxemia has been recognized to be closely accompanied with type 2 diabetes mellitus (T2DM) and is responsible for many diabetic complications. Recent study suggests the potential role of butyrate, a short-chain fatty acid (SCFA) from microbiota metabolite, on T2DM. Gut-leak is a key event in diabetic-endotoxemia. To investigate if butyrate could ameliorate diabetic-endotoxemia, both in vivo and in vitro experiments were carried out in the present study. The effect of butyrate supplementation on blood HbA1c and inflammatory cytokines were determined in db/db mice; gut barrier integrity and expression of tight junction proteins were investigated both in vivo and in vitro Oral butyrate administration significantly decreased blood HbA1c, inflammatory cytokines and LPS in db/db mice; inflammatory cell infiltration was reduced, and gut integrity and intercellular adhesion molecules were increased as detected by HE staining, immunohistochemistry and Western blot. By gut microbiota assay, ratio of Firmicutes:Bacteroidetes for gut microbiota was reduced by butyrate. In Caco-2 cells, butyrate significantly promoted cell proliferation, decreased inflammatory cytokines' secretion, enhanced cell anti-oxidative stress ability and preserved the epithelial monocellular integrity, which was damaged by LPS. The present findings demonstrated that butyrate supplementation could ameliorate diabetic-endotoxemia in db/db mice via restoring composition of gut microbiota and preserving gut epithelial barrier integrity.

Effect of oxidative stress from nanoscale TiO2 particles on a Physarum polycephalum macroplasmodium under dark conditions.

Information regarding the effect of nanoscale titanium dioxide particles (nTiO2) on the environment under dark conditions is scarce, and the effect of nTiO2 on fungi is largely unknown. Due to its huge size and high sensitivity to external stimuli, the slime mold fungi cell, Physarum polycephalum macroplasmodium, was utilized as a novel subject for the toxicity investigations in the present study, and oxidative stress from nTiO2 on the macroplasmodium was assessed under dark conditions. Short exposure (2-3 h) caused an intracellular reactive oxygen species (ROS) imbalance, and an anti-oxidative mechanism was activated from intermediate doses of nTiO2 (5-18 mg/mL). At long exposure times (~3 days), relatively low doses of nTiO2 (≤9 mg/mL) stimulated the growth of macroplasmodium and oxidative stress without DNA damage, whereas higher doses of nTiO2 (≥15 mg/mL) led to growth inhibition, significant DNA oxidative damage, and activation of the DNA single-strand repairing system. Although DNA oxidative damage was decreased to the same level as the control group by the supplementation of the anti-oxidant vitamin C, growth of the macroplasmodium failed to be completely restored. We inferred that nTiO2 induced a complicated toxicity effect on P. polycephalum in addition to DNA oxidative damage. Taken as a whole, the present study implied the probability of using P. polycephalum macroplasmodium for toxicity studies at the single-cell level, indicating that nTiO2 could induce oxidative stress or damage in P. polycephalum even under dark conditions and suggesting that the release of nTiO2 could lead to a growth imbalance of slime molds in the environment.

Responsive electrical stimulation suppresses epileptic seizures in rats.

BACKGROUND: A responsive electrical stimulation pattern based on our recently developed novel seizure prediction method was designed to suppress the penicillin-induced epileptic seizures. METHODOLOGY: Seizures were induced by Penicillin injection at rat cortex. A responsive electrical stimulation system was triggered prior to seizures predicted with phase synchronisation. Rats with induced seizures were stimulated by the electrical pulses at a responsive or 1 Hz periodic pattern of an open system. The effectiveness of stimulation on seizures suppression was assessed by measuring the average number and duration of seizures per hour. RESULTS: The prediction algorithm reliably identified seizures in real time and triggered the responsive stimulation. This type of electrical stimulation dramatically suppressed seizure activity and the performance was better than the open stimulation system with fewer and shorter seizures. CONCLUSIONS: A responsive electrical stimulation system triggered by the phase synchronisation prediction is able to significantly suppress seizures. SIGNIFICANCE: Responsive electrical stimulation could achieve superior treatment performance and reduce power consumption and side effects.

Low- and high-frequency electric cortical stimulation suppress the ferric chloride-induced seizures in rats.

The clinic treatment of epilepsy with epileptic foci overlapped with eloquent cortex is not satisfactory. In this study we investigated the direct effects of low- and high-frequency electric cortical stimulation (ECS) on ferric chloride-induced seizures in the experimental rats. Results showed that spontaneous seizures were observed in all rats during the EEG recording after the intracortical injection of ferric chloride solution into left sensorimotor cortex. One-hertz or 100-Hz ECS with 0.3 ms duration and 0.1 mA amplitude square pulses in 1h on the cortical lesioned area significantly decreased the number of seizures compared with that of the non-stimulation control group. The mean duration time of seizures in 1-Hz or 100-Hz groups was apparently shorter than that in the control group. In brief, this study showed that both low- and high-frequency ECS suppressed the seizures induced by ferric chloride in rats, indicating their potential treatment effects on epilepsy in clinic.

[Clinical study of super crush-run Tongxinluo capsule on treatment of stroke].

OBJECTIVE: To evaluate the clinical efficacy and security of super crush-run tong xinluo capsule (SCTXLC) for apoplexy due to energy-deficiency and blood-stasis. METHOD: The randomised controlled double blind non-inferiority trial versus paroxetine, parallel contrast, different Kinds of Techniques and dosage, the clinical trial design was adopted, 144 patients with stroke of convalescent stage were selected by 2 group, which course of diseases was in 2 weekens to 3 months, neurological deficit scores was 8 to 30, grade of acaties of daily living scores was 2 to 5. the treatment group (n = 72) received SCTXLC 0.26 g (a capsule), 4 capsules at a time, three times a day, while that of the control group (n = 72) received common crush-run tong xinluo capsule (CCTXLC) 0.38 g (a capsule), 4 capsules at a time, three times a day, the therapeutic course for both groups was 28 d. RESULT: The synthesis total effective rates of the stroke in treatment group and control group were 91.3% and 87.3% respectively, showing no significant difference. The Lower Bound Upper Bound of Asymptotic 95% Confidence Interval of the total effective rates difference is -4.57%, over the beforehand Lower Bound of 15%, non-inferiority trial versus paroxetine was eligible. The adverse reactions occurred was 1 patient in the treatment group and 2 patients in control group in clinical trial. CONCLUSION: SCTXLC has definite effect for apoplexy due to energy-deficiency and blood-stasis, the efficacy in the treated group was equal to that in the control group, and favourable satety for usage.

Clinical study of super crush-run Tongxinluo capsule on treatment of stroke / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy and security of super crush-run tong xinluo capsule (SCTXLC) for apoplexy due to energy-deficiency and blood-stasis.</p><p><b>METHOD</b>The randomised controlled double blind non-inferiority trial versus paroxetine, parallel contrast, different Kinds of Techniques and dosage, the clinical trial design was adopted, 144 patients with stroke of convalescent stage were selected by 2 group, which course of diseases was in 2 weekens to 3 months, neurological deficit scores was 8 to 30, grade of acaties of daily living scores was 2 to 5. the treatment group (n = 72) received SCTXLC 0.26 g (a capsule), 4 capsules at a time, three times a day, while that of the control group (n = 72) received common crush-run tong xinluo capsule (CCTXLC) 0.38 g (a capsule), 4 capsules at a time, three times a day, the therapeutic course for both groups was 28 d.</p><p><b>RESULT</b>The synthesis total effective rates of the stroke in treatment group and control group were 91.3% and 87.3% respectively, showing no significant difference. The Lower Bound Upper Bound of Asymptotic 95% Confidence Interval of the total effective rates difference is -4.57%, over the beforehand Lower Bound of 15%, non-inferiority trial versus paroxetine was eligible. The adverse reactions occurred was 1 patient in the treatment group and 2 patients in control group in clinical trial.</p><p><b>CONCLUSION</b>SCTXLC has definite effect for apoplexy due to energy-deficiency and blood-stasis, the efficacy in the treated group was equal to that in the control group, and favourable satety for usage.</p>

Inhibitory effects of alpha-zearalenol on angiotensin II-induced integrin beta3 mRNA via suppression of nuclear factor-kappaB.

OBJECTIVE: To investigate the effect of alpha-zearalenol on angiotensin II-induced beta3 integrin mRNA expression in human umbilical vein endothelial cells (HUVECs). METHODS: The mRNA level in integrin beta3 was determined by reverse transcription-polymerase chain reaction. Endothelial NF-kappaB activity was determined by the luciferase activity assay of plasmid NF-kappaB-LUC. RESULTS: The angiotensin II-induced beta3 integrin mRNA expression was inhibited by alpha-zearalenol and 17beta-estradiol (10 nmol/L -1 micromol/L), but not influenced by ICI 182, 780, a pure competitive antagonist for estrogen receptor or a nitric oxide inhibitor Nomega-Nitro-L-arginine methyl ester hydrochloride. Alpha-zearalenol and 17beta-estradiol suppressed the angiotensin II-induced activation of NF-kappaB in endothelial cells. CONCLUSION: Alpha-zearalenol inhibits angiotensin II-induced integrin beta3 mRNA expression by suppressing NF-kappaB activation in endothelial cells.