The Yin and Yang of the protein corona on the delivery journey of nanoparticles.

Nanoparticles-based drug delivery systems have attracted significant attention in biomedical fields because they can deliver loaded cargoes to the target site in a controlled manner. However, tremendous challenges must still be overcome to reach the expected targeting and therapeutic efficacy in vivo. These challenges mainly arise because the interaction between nanoparticles and biological systems is complex and dynamic and is influenced by the physicochemical properties of the nanoparticles and the heterogeneity of biological systems. Importantly, once the nanoparticles are injected into the blood, a protein corona will inevitably form on the surface. The protein corona creates a new biological identity which plays a vital role in mediating the bio-nano interaction and determining the ultimate results. Thus, it is essential to understand how the protein corona affects the delivery journey of nanoparticles in vivo and what we can do to exploit the protein corona for better delivery efficiency. In this review, we first summarize the fundamental impact of the protein corona on the delivery journey of nanoparticles. Next, we emphasize the strategies that have been developed for tailoring and exploiting the protein corona to improve the transportation behavior of nanoparticles in vivo. Finally, we highlight what we need to do as a next step towards better understanding and exploitation of the protein corona. We hope these insights into the "Yin and Yang" effect of the protein corona will have profound implications for understanding the role of the protein corona in a wide range of nanoparticles.

Anti-Hyperglycemic Agents in the Adjuvant Treatment of Sepsis: Improving Intestinal Barrier Function.

Intestinal barrier injury and hyperglycemia are common in patients with sepsis. Bacteria translocation and systemic inflammatory response caused by intestinal barrier injury play a significant role in sepsis occurrence and deterioration, while hyperglycemia is linked to adverse outcomes in sepsis. Previous studies have shown that hyperglycemia is an independent risk factor for intestinal barrier injury. Concurrently, increasing evidence has indicated that some anti-hyperglycemic agents not only improve intestinal barrier function but are also beneficial in managing sepsis-induced organ dysfunction. Therefore, we assume that these agents can block or reduce the severity of sepsis by improving intestinal barrier function. Accordingly, we explicated the connection between sepsis, intestinal barrier, and hyperglycemia, overviewed the evidence on improving intestinal barrier function and alleviating sepsis-induced organ dysfunction by anti-hyperglycemic agents (eg, metformin, peroxisome proliferators activated receptor-γ agonists, berberine, and curcumin), and summarized some common characteristics of these agents to provide a new perspective in the adjuvant treatment of sepsis.

Stereoselective hydrogen atom transfer to acyclic radicals: a switch enabling diastereodivergent borylative radical cascades.

Radical cascade reactions are powerful tools to construct structurally complex molecules. However, the stereochemical control of acyclic radical intermediates remains a persistent challenge, due to the low differentiation between the two faces of these species. This hurdle further makes stereodivergent synthesis rather more difficult to be accomplished, in particular for intermediates resulted from complex cascades. Here we report an efficient strategy for stereoselective hydrogen atom transfer (HAT) to acyclic carbon radicals, which are generated via N-heterocyclic carbene (NHC)-boryl radicals triggered addition-translocation-cyclization cascades. A synergistic control by the NHC subunit and a thiol catalyst has proved effective for one facial HAT, while a ZnI2-chelation protocol allows for the preferential reaction to the opposite face. Such a stereoselectivity switch enables diastereodivergent construction of heterocycles tethering a boron-substituted stereocenter. Mechanistic studies suggest two complementary ways to tune HAT diastereoselectivity. The stereospecific conversions of the resulting boron-handled products to diverse functionalized molecules are demonstrated.

[The physiological and psychological mechanisms of infra-slow oscillation].

Infra-slow oscillation (ISO) is a kind of brain rhythm between 0.01 and 0.5 Hz. ISO is widely distributed in multiple brain regions. As an important psychophysiological activity, the ISO interacts with high-frequency neural rhythm via cross-frequency coupling, but has different activity patterns from high-frequency neural activity. Physiologically, the ISO may be generated by the dynamic activity of thalamus, glia, and ions. Psychologically, the frequency, amplitude, and phase of ISO could all regulate cognitive activities, but in different ways. Investigations on the ISO expands the neural rhythm research to lower frequency range, further promoting the construction of rhythmic theory of brain function.

Application of Artificial Intelligence in the Establishment of an Association Model between Metabolic Syndrome, TCM Constitution, and the Guidance of Medicated Diet Care.

BACKGROUND: This study conducted exploratory research using artificial intelligence methods. The main purpose of this study is to establish an association model between metabolic syndrome and the TCM (traditional Chinese medicine) constitution using the characteristics of individual physical examination data and to provide guidance for medicated diet care. METHODS: Basic demographic and laboratory data were collected from a regional hospital health examination database in northern Taiwan, and artificial intelligence algorithms, such as logistic regression, Bayesian network, and decision tree, were used to analyze and construct the association model between metabolic syndrome and the TCM constitution. Findings. It was found that the phlegm-dampness constitution (90.6%) accounts for the majority of TCM constitution classifications with a high risk of metabolic syndrome, and high cholesterol, blood glucose, and waist circumference were statistically significantly correlated with the phlegm-dampness constitution. This study also found that the age of patients with metabolic syndrome has been advanced, and shift work is one of the risk indicators. Therefore, based on the association model between metabolic syndrome and TCM constitution, in the future, metabolic syndrome can be predicted through the syndrome differentiation of the TCM constitution, and relevant medicated diet care schemes can be recommended for improvement. CONCLUSION: In order to increase the public's knowledge and methods for mitigating metabolic syndrome, in the future, nursing staff can provide nonprescription medicated diet-related nursing guidance information via the prediction and assessment of the TCM constitution.

Total alkaloids from Alstonia scholaris inhibit influenza a virus replication and lung immunopathology by regulating the innate immune response.

BACKGROUND: Alstonia scholaris is a folk medicine used to treat cough, asthma and chronic obstructive pulmonary disease in China. Total alkaloids (TA) from A. scholaris exhibit anti-inflammatory properties in acute respiratory disease, which suggests their possible anti-inflammatory effect on influenza virus infection. PURPOSE: To assess the clinical use of TA by demonstrating their anti-influenza and anti-inflammatory effects and the possible mechanism underlying the effect of TA on influenza A virus (IAV) infection in vitro and to reveal the inhibitory effect of TA on lung immunopathology caused by IAV infection. METHODS: Antiviral and anti-inflammatory activities were assessed in Madin-Darby canine kidney (MDCK) and A549 cells and U937-derived macrophages infected with influenza A/PR/8/34 (H1N1) virus. Proinflammatory cytokine levels were measured by real-time quantitative PCR and Bio-Plex assays. The activation of innate immune signaling induced by H1N1 virus in the absence or presence of TA was detected in A549 cells by Western blot. Furthermore, mice were infected intranasally with H1N1 virus and treated with TA (50, 25 and 12.5 mg/kg/d) or oseltamivir (60 mg/kg/d) for 5 days in vivo. The survival rates and body weight were recorded, and the viral titer, proinflammatory cytokine levels, innate immune cell populations and histopathological changes in the lungs were analyzed. RESULTS: TA significantly inhibited viral replication in A549 cells and U937-derived macrophages and markedly reduced cytokine and chemokine production at the mRNA and protein levels. Furthermore, TA blocked the activation of pattern recognition receptor (PRR)- and IFN-activated signal transduction in A549 cells. Critically, TA also increased the survival rate, reduced the viral titer, suppressed proinflammatory cytokine production and innate immune cell infiltration and improved lung histopathology in a lethal PR8 mouse model. CONCLUSION: TA exhibits anti-viral and anti-inflammatory effects against IAV infection by interfering with PRR- and IFN-activated signal transduction.

[Altitudinal variation of floral organs in Saussurea przewalskii and its relationship with the number and mass of seeds]. / å¼¯é½¿é£Žæ¯›èŠèŠ±éƒ¨å™¨å®˜çš„æµ·æ‹”å˜å¼‚åŠå ¶ä¸Žç§å­è´¨é‡å’Œæ•°ç›®çš„å ³ç³».

We examined the variation of floral organs of Sausssurea przewalskii along altitude and its relationship with the number and mass of seeds from 12 populations in the northeastern edge of Qinghai-Tibetan Plateau, China. At the altitude of 3500-4500 m, the filament length, anther length, column length and style branch length were 0.52-1.01, 0.23-0.63, 0.74-1.58, and 0.11-0.22 cm, respectively. All the indices significantly increased with altitude, while the number of pollens (26.5×104-73.5×104) significantly decreased. There was a significant negative correlation between the lengths of filament, style, column branches and pollen numbers, and a significant positive correlation between column length and filament length. The number of seeds was negatively correlated with the lengths of filament, column and style branches, but positively correlated with the number of pollen. The hundred kernals weight was positively correlated with the length of the filament, column and style branches, and negatively correlated with the number of pollen. With the increases of altitude, S. przewalskii extends the length of flower organs to increase the pollen carrying capacity and input of insects in the flowering period, and produces large seeds with more competitive advantage and survival rate in fruiting stage to improve its fitness.

Copper-mediated oxidative transformation of N-allyl enamine carboxylates toward synthesis of azaheterocycles.

A method for synthesis of 3-azabicyclo[3.1.0]hex-2-enes has been developed by intramolecular cyclopropanation of readily available N-allyl enamine carboxylates. Two complementary reaction conditions, CuBr-mediated aerobic and CuBr2-catalyzed-PhIO2-mediated systems effectively induced stepwise cyclopropanation via carbocupration of alkenes. Oxidative cyclopropane ring-opening of 5-substituted 3-azabicyclo[3.1.0]hex-2-enes was also developed for synthesis of highly substituted pyridines. In addition, diastereoselective reduction of 3-azabicyclo[3.1.0]hex-2-enes to 3-azabicyclo[3.1.0]hexanes was achieved using NaBH3CN in the presence of acetic acid.

Copper-mediated aerobic synthesis of 3-azabicyclo[3.1.0]hex-2-enes and 4-carbonylpyrroles from N-allyl/propargyl enamine carboxylates.

Synthetic methods for 3-azabicyclo[3.1.0]hex-2-enes and 4-carbonylpyrroles have been developed that use copper-mediated/catalyzed reactions of N-allyl/propargyl enamine carboxylates under an O(2) atmosphere and involve intramolecular cyclopropanation and carbooxygenation, respectively. These methodologies take advantage of orthogonal modes of chemical reactivity of readily available N-allyl/propargyl enamine carboxylates; the complementary pathways can be accessed by slight modification of the reaction conditions.