Temperature-sensitive hydrogel releasing pectolinarin facilitate scarless wound healing.

The dressing that promotes scarless healing is essential for both normal function and aesthetics after a wound. With a deeper understanding of the mechanisms involved in scar formation during the wound healing process, the ideal dressing becomes clearer and more promising. For instance, the yes-associated transcriptional regulator (YAP) has been extensively studied as a key gene involved in regulating scar formation. However, there has been limited attention given to pectolinarin, a natural flavonoid that may exhibit strong binding affinity to YAP, in the context of scarless healing. In this study, we successfully developed a temperature-sensitive Pluronic@F-127 hydrogel as a platform for delivering pectolinarin to promote scarless wound healing. The bioactive pectolinarin was released from the hydrogel, effectively enhancing endothelial cell migration, proliferation and the expression of angiogenesis-related genes. Additionally, a concentration of 20 µg/mL of pectolinarin demonstrated remarkable antioxidant ability, capable of counteracting the detrimental effects of reactive oxygen species (ROS). Our results from rat wound healing models demonstrated that the hydrogel accelerated wound healing, promoting re-epithelialization and facilitating skin appendage regeneration. Furthermore, we discovered that a concentration of 50 µg/mL of pectolinarin incorporated to the hydrogel exhibited the most favourable outcomes in terms of promoting wound healing and minimizing scar formation. Overall, our study highlights that the significant potential of locally released pectolinarin might substantially inhibit YAP and promoting scarless wound healing.

Association between falls in elderly and the number of chronic diseases and health-related behaviors based on CHARLS 2018: health status as a mediating variable.

OBJECTIVE: Falling is one of the main causes of death and morbidity in the elderly. This study aims to explore the association between elderly patients with chronic diseases and their health-related behaviors and falls in the elderly, and to provide clues for the prevention and intervention of injuries caused by falls in the elderly. METHODS: Based on the basic demographic characteristics data, number of chronic diseases, health-related behaviors, and physical and mental health data of 5867 elderly people aged 60 and above in the 2018 CHARLS data, this paper used ordered logit regression to analyze the correlation between chronic diseases and their health-related behaviors and falls of Chinese elderly. On this basis, it also distinguishes whether there is care or not, explores whether the related factors of falls of elderly people will be different, and tests the intermediary effect of health status to further explore its mechanism. RESULTS: The number of chronic diseases and health-related behaviors in the four dimensions of sleeptime, drinking, smoking, and activity are significantly correlated with falls in the elderly. Among them, health status plays a significant mediating role in the relationship of the number of chronic diseases and sleeptime and activity on the falls of the elderly. In addition, compared with the elderly without care, the risk of falls in the elderly in care is only related to the number of chronic diseases and sleeptime, while the elderly without care is related to the number of chronic diseases and multiple factors such as smoking, drinking and activity. CONCLUSION: Falls are significantly associated with chronic disease and health-related behaviors, while risk or protective factors for falls vary according to whether older adults are cared for. Therefore, targeted interventions can be made for the factors that affect the fall of the elderly according to different situations.

Do medical treatment choices affect the health of chronic patients in middle and old age in China?-Evidence from CHARLS 2018.

Different medical treatment choices may affect the health of patients with chronic diseases. This study aims to assess the relationship between treatment choices, including the use of traditional Chinese medicine (TCM), and the health levels of middle-aged and elderly patients with six chronic diseases. The sample data comes from China Health and Retirement Longitudinal Study (CHARLS 2018). Basic conditions, medical choices and health status of patients are incorporated. The ordered Logit and Logit regression models are used to analyze and compare the effects of six chronic disease patients' medical options on their self-rated health (SRH) and depression. The overall average score of SRH is the highest in patients with heart disease (the worst in SRH), which is 3.433. Arthritis patients have the highest overall depression average score (depression) at 0.444. Under the premise of controlling a variety of socio-demographic factors, compared with the non-treatment group, taking TCM has a significant positive effect on SRH of patients with five diseases except hypertension. Both taking western medicine (WM) and taking integrated Chinese and Western medicine (IM) have a significant positive effect on SRH scores of patients with six chronic diseases in middle and old age. Taking TCM has effect on depression of patients with heart or stomach diseases, and taking WM and IM affects depression of middle-aged and elderly chronic patients except diabetes. Taking IM has a greater effect on SRH and depression of chronically ill patients, followed by taking WM, and the effect of taking TCM is relatively small, which is related to the development stage of the disease. Therefore, in the future, the control and treatment of chronic diseases in the middle and late stages can be discussed from the perspective of integrated traditional Chinese and western medicine, but attention should be paid to drug interactions. In order to improve the treatment rate and health level of patients with chronic diseases, their economic burden should be reduced, and they should be guided to choose more reasonable treatment methods.

Research on grandchild care and depression of chinese older adults based on CHARLS2018: the mediating role of intergenerational support from children.

BACKGROUND: There may be differences in gender and marital status in the impact of grandchild care on the depression of the Chinese older adults. This research explores the effect of grandchild care on the depression of Chinese older adults of different genders and marital status, and explores the mediating role of intergenerational support from children between grandchild care and depression. METHODS: This research uses the data of 3540 Chinese older adults from the China Health and Retirement Longitudinal Study (CHARLS) in 2018. The OLS model is used to analyze the effect of grandchild care on the depression of the older adults. and the older adults are classified according to gender and marital status, and the differences in the effect of grandchild care on the depression of the elderly of different genders and marital status is explored. Finally, the bootstrap method is used to test the mediating effect of intergenerational support from children. RESULTS: The research finds that grandchild care has a significant impact on the depression of the older adults in China, and providing grandchild care can significantly reduce the depression of the older adults. The effect of grandchild care on the depression of the older adults is different between different genders and marital status. After categorizing the older adults by gender, the grandchild care only has a significant impact on the depression of female older adults; after classified by marital status, grandchild care only has a significant impact on the depression of the older adults who don't have a spouse. The mediating effect analysis shows that both children's emotional support and children's economic support have a mediating effect between grandchild care and depression of the older adults. CONCLUSION: The depression of the Chinese older adults is affected by grandchild care, and this effect is more prominent in female older adults and the older adults who don't have a spouse. The society should support and encourage capable older adults to participate in grandchild care, and children should also provide more intergenerational support to the older adults who provide grandchild care, so as to further play the role of grandchild care in relieving depression of the older adults.

Development of high barrier-coated white cardboard for fruit preservation.

Environment-friendly and biodegradable packaging materials have attracted widespread attention. Development of green solutions to extend the fruit shelf life and address fruit preservation thus has a far-reaching impact. In this study, high-barrier white cardboard (WC) was prepared by a facile coating method. Compared with the WC substrate, the WVP value of the polyvinylidene chloride (PVDC) emulsion-coated WC (3.46 × 10-11 g m m-2 s-1 kPa-1) decreased 73.8% and the OP value (14.8 cm3 m-2 day-1·Pa-1) decreased 61.9%. In addition, the mechanical properties of the PVDC emulsion-coated WC increased significantly. The weight loss rate and decay rate of the stored fruits packaged with PVDC emulsion-coated WC decreased by about 5%. The high barrier PVDC emulsion-coated WC with excellent mechanical properties, good barrier effect, and preservation function was successfully prepared. Benefitting from these investigated characteristics, the obtained coated WC can be used to package fruits to reduce water loss and delay ripening, and thus extend their shelf life, exhibiting a favorable effect on blueberry and grape storage. Overall, the fabricated eco-friendly coated white cardboard has shown great potential for biodegradable packaging applications. We believe the current work presents an approach to address perishable fruit preservation and provide a supplement alternative.

Dynamic changes in permafrost distribution over China and their potential influencing factors under climate warming.

As a major component of the cryosphere, permafrost plays important roles in the climate system and land surface processes of the Earth. Owing to the rapidly warming climate, permafrost over the globe has degraded in recent decades. However, quantifying the distribution and temporal changes in permafrost is challenging. In this study, we modified the widely used surface frost number model by considering the spatial distribution of soil hydrothermal properties and then revisited the spatiotemporal patterns of permafrost distribution and its changes during the past decades (1961-2017) in China. We found that the modified surface frost number model performs well in simulating permafrost extent in China, with the overall accuracy and kappa coefficients being 0.92 and 0.78 in the calibration (1980s) and 0.94 and 0.77 in the validation period (2000s). Based on the modified model, we also found that permafrost extent in China demonstrated a significant decreasing trend over the past decades, especially on the Qinghai-Tibet Plateau (QTP), with a trend of -1.15 × 104 km2/yr (P < 0.01). Moreover, there is a significant relationship between ground surface temperature and permafrost distribution area, with the R2 being 0.41, 0.42, and 0.77 in NE and NW China and on the QTP. The sensitivity of permafrost extent to ground surface temperature in NE China, NW China, and the QTP, respectively, was -8.56 × 104, -1.97 × 104, and -34.60 × 104 km2/°C, respectively. Permafrost degradation has accelerated since the late 1980s, possibly due to increased climate warming. This study is of great significance for improving permafrost distribution simulation at large spatial scales (trans-regional) and for offering vital information for adapting to climate change in cold regions.

Topography regulates the responses of water partitioning to climate and vegetation seasonality.

This study investigates the relationships between water partitioning, climate and vegetation dynamics, and their influencing factors, using a method combining scenario analysis and a modified Choudhury's formula that considers climate and vegetation seasonality. Comparing the results in ten major catchments in southwestern China with similar climate and vegetation but drastically different topography, shows that the climate and vegetation seasonality jointly control the variance in the catchment parameter n of the Choudhury's formula (R2 = 0.81 ± 0.13), which determines the amount of water being depleted through evapotranspiration under a given climate. What's interesting is that the relationships among the parameter n, climate and vegetation seasonality are affected obviously by the catchment's properties, such as the POK (portion of karst landform), MS (mean slope) and MTWI (mean topographic wetness index), NDVI and aridity index (AI). Notably, the parameter n is affected more (less) by climate and vegetation seasonality in catchments with better vegetation and drier climate (with steeper topography). Moreover, the relative contribution from the changes in precipitation (P) and potential evapotranspiration (PET) amount is negatively correlated to MS (r = 0.87, α < 0.05), and that from climate seasonality is positively correlated to MS (r = -0.81, α < 0.05), indicating that changes in P and PET amount are less important, but climate seasonality plays a more important role in controlling water partitioning in steeper catchments. The results demonstrate that the topography has an important role in influencing the responses of water partitioning to climate and vegetation seasonality.

What roles can water-stressed vegetation play in agricultural droughts?

Two-way feedbacks exist between water-stressed vegetation and agricultural drought. Previous studies have focused mainly on the responses of vegetation to agricultural droughts but rarely on those of agricultural droughts to vegetation. Based on a new drought index (AgDI) that incorporates dynamic climatic and vegetation information, this study evaluated the impacts of climate and vegetation variabilities on agricultural droughts in 20 catchments in southwestern China, a region frequently hit by droughts. Results showed that the drought-stressed vegetation tended to alleviate agricultural droughts, and the drought-alleviating ability of vegetation was affected by vegetation types and the magnitudes of the changes in climate. Compared to other types of vegetation, the natural forest generally has a greater ability to affect agricultural drought. Overall, the relative contribution (mean of 29.9 ± 24.6%) of changes in vegetation to agricultural drought was at least comparable to those of the changes in potential evapotranspiration (mean of 14.4 ± 12.7%). Results also showed that even though vegetation has the ability to alleviate agricultural droughts, the changes in agricultural droughts were still dominated by climate changes, especially precipitation (mean relative contribution of 55.7 ± 24.2%).

How Do Intergenerational Economic Support, Emotional Support and Multimorbidity Affect the Catastrophic Health Expenditures of Middle-Aged and Elderly Families?-Evidence From CHARLS2018.

Objectives: The elderly face multiple vulnerabilities such as health, economy and society, and are prone to catastrophic health expenditures. This study aims to analyze the impact of children's intergenerational economic support, emotional support, and illness on the catastrophic health expenditures of middle-aged and elderly families. Methods: Using China Health and Retirement Longitudinal Study (CHARLS 2018) data to calculate the catastrophic health expenditure of Chinese households as the dependent variable. Taking children's intergenerational economic support, emotional support and multimorbidity as core independent variables, gender, age, marital status, medical insurance and other variables as control variables, and perform logistic regression analysis. According to the heterogeneity analysis of age and gender, the impact of intergenerational economic support, emotional support and multimorbidity on the catastrophic health expenditure of middle-aged and elderly families is explored. Results: When catastrophic health expenditures occur in middle-aged and elderly families, the children's intergenerational economic support will increase significantly, especially in families with members aged 60-74. Children's emotional support can effectively reduce the risk of catastrophic health expenditures for middle-aged and elderly families. Compared with children's intergenerational economic support and emotional support, the impact of multimorbidity on the catastrophic health expenditures of middle-aged and elderly families is the most significant. Suffering from multimorbidity can increase the risk of catastrophic health expenditures for middle-aged and elderly families, especially families with male members suffering from multiple diseases. Conclusions: It is recommended that we should do a good job in popularizing the knowledge of chronic diseases to minimize the occurrence of multimorbidity. The government should establish group medical insurance related to chronic disease diagnosis. According to the severity of the disease or the special circumstances of the patient, the level of medical insurance reimbursement is divided in detail, especially for chronic disease clinics and drug reimbursement. Children should be encouraged to strengthen the emotional connection and effective care of the elderly, focusing on the elderly 60-74 years old, in order to reduce their care pressure and maintain the physical and mental health of the elderly.

IKKß mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.

Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKß) is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B (IκBα) and then activate nuclear factor kappa-B (NF-κB). Inhibition of IKKß has been a therapeutic strategy for inflammatory and autoimmune diseases. Here we report that IKKß is constitutively activated in healthy donors and healthy Ikkß C46A (cysteine 46 mutated to alanine) knock-in mice although they possess intensive IKKß-IκBα-NF-κB signaling activation. These indicate that IKKß activation probably plays homeostatic role instead of causing inflammation. Compared to Ikkß WT littermates, lipopolysaccharides (LPS) could induce high mortality rate in Ikkß C46A mice which is correlated to breaking the homeostasis by intensively activating p-IκBα-NF-κB signaling and inhibiting phosphorylation of 5' adenosine monophosphate-activated protein kinase (p-AMPK) expression. We then demonstrated that IKKß kinase domain (KD) phosphorylates AMPKα1 via interacting with residues Thr183, Ser184, and Thr388, while IKKß helix-loop-helix motifs is essential to phosphorylate IκBα according to the previous reports. Kinase assay further demonstrated that IKKß simultaneously catalyzes phosphorylation of AMPK and IκBα to mediate homeostasis. Accordingly, activation of AMPK rather than inhibition of IKKß could substantially rescue LPS-induced mortality in Ikkß C46A mice by rebuilding the homeostasis. We conclude that IKKß activates AMPK to restrict inflammation and IKKß mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.

Do Drug Accessibility and OOP Burden Affect Health-Related Quality of Life of Patients With Chronic Diseases? - EQ-5D-5L Evaluation Evidence From Five Districts in China.

Purpose: The dependence of patients with chronic diseases on drugs may affect their health-related quality of life (HRQoL). This study aims to assess the relationship between the direct economic burden caused by out-of-pocket (OOP) payments, drug accessibility, sociodemographic characteristics, and health-related quality of life. Methods: 1,055 patients with chronic diseases from Gansu, Hebei, Sichuan, Zhejiang, and Tianjin were investigated. Data collection included basic conditions and economic and health insurance conditions of patients with chronic diseases. The CLAD and Tobit regression models were used to analyze and compare the health-related quality of life and influencing factors of patients with chronic diseases in five districts. Differentiated analysis was conducted through sub-sample regression to explore the variable health effects of patients with single and multiple diseases. Results: A total of 1,055 patients with chronic diseases participated in the study, 54.4% of whom were women. The overall average utility score was 0.727, of which Sichuan Province was the highest with 0.751. Participants reported the highest proportion of pain/discomfort problems, while patients reported the least problems with self-care. The improvement of drug accessibility and the reduction of the burden of out-of-pocket expenses have significant positive effects on HRQoL. Various sociodemographic factors such as age and gender also have significant impact on HRQoL of patients with chronic diseases. HRQoL of patients with multiple chronic diseases is more affected by various influencing factors than that of patients with single disease. Conclusion: In order to improve the quality of life of patients with chronic diseases, it is of great importance to ensure the accessibility of drugs and reduce patients' medication burden. Future focus should shift from preventing and controlling chronic diseases as individual diseases to meeting the comprehensive health needs of people suffering from multiple diseases.

Controllable Generation of Reactive Oxygen Species on Cyano-Group-Modified Carbon Nitride for Selective Epoxidation of Styrene.

The controlled generation of reactive oxygen species (ROS) to selectively epoxidize styrene is a grand challenge. Herein, cyano-group-modified carbon nitrides (CNCY x and CN-T y ) are prepared, and the catalysts show better performance in regulating ROS and producing styrene oxide than the cyano-free sample. The in situ diffuse reflectance infrared and density functional theory calculation results reveal that the cyano group acts as the adsorption and activation site of oxygen. X-ray photoelectron spectroscopy and NMR spectrum results confirm that the cyano group bonds with the intact heptazine ring. This unique structure could inhibit H2O2 and ⋅OH formation, resulting in high selectivity of styrene oxide. Furthermore, high catalytic activity is still achieved when the system scales up to 2.7 L with 100 g styrene under solar light irradiation. The strategy of cyano group modification gives a new insight into regulating spatial configuration for tuning the utilization of oxygen-active species and shows potential applications in industry.

Characterization of covalent protein modification by triclosan in vivo and in vitro via three-dimensional liquid chromatography-mass spectrometry: New insight into its adverse effects.

Triclosan (TCS), an antimicrobial agent widely used in personal care products and ubiquitously exists in environment, has drawn increasing concern due to its potential to exert multiple adverse effects, ranging from endocrine disruption to carcinogenesis. However, the mechanism of these adverse effects is still not fully elucidated. More and more studies have shown that chemical reactive metabolites (RMs) covalently binding to proteins is a possible reason for these adverse effects, but there is still a lack of appropriate methods to predict or evaluate these adverse effects due to the extremely low abundance of the modified proteins in complex biological samples. In this study, we attempted to address this problem and investigate the possible mechanism of TCS adverse effects by a shotgun proteomics approach based on three-dimensional-liquid chromatography-mass spectrometry (3D-LC-MS). First, the in vitro incubation with model amino acids and protein in microsomes showed that TCS could react with cysteine residue of proteins through 3 types of RMs. Then, a 3D-LC-MS approach was developed to sensitively determine the low abundant modified proteins, which resulted in the identification of 45 TCS-modified proteins, including albumin, haptoglobin and NR1I2, in rats. STRING analysis indicated that these modified proteins mainly were involved in reproductive and development system, endocrine and immune system, and carcinogenesis, which were in accord with the main reported TCS-induced adverse effects and suggested that the covalent modification of TCS RMs for proteins might affect their activities and functions, thus inducing serious adverse effects. This study provided a new insight into the mechanism of TCS adverse effects and may serve as a valuable method to predict or evaluate adverse effects of ubiquitous chemicals.

Enhanced photocatalytic hydrogen production from aqueous-phase methanol reforming over cyano-carboxylic bifunctionally-modified carbon nitride.

Polymeric carbon nitride is a promising candidate for metal-free photocatalysis, but it is hampered by low activity due to poor carrier separation efficiency and lack of active sites. We have constructed a bifunctionally-modified structure, containing cyano groups internally and carboxyl groups on the surface, that was about 205 times more active than unmodified carbon nitride. The internal cyano groups enhanced the photoelectric performance of carbon nitride, while the surface carboxyl groups acted as active sites to promote hydrogen production. It is anticipated that this work will inform the rational design of polymeric carbon nitride and inspire similar attempts to modify polymers.

Effects of vegetation restoration on soil quality in degraded karst landscapes of southwest China.

Vegetation restoration was implemented to control soil erosion in the karst regions of southwest China. It is essential to assess the soil function and quality scientifically during this process and to adopt suitable management practices for this area. However, few studies have been conducted to comprehensively evaluate the effect of vegetation restoration on soil quality in this severely eroded karst area. By taking 302 soil samples from 11 vegetation types, this study investigated the influence of different types of vegetation restoration on soil quality using an integrated soil quality index (SQI) and a generalized linear model (GLM). Vegetation types had significant effects on soil properties and thus on soil quality. SQI was developed by using TN, TP, TK, AP, and clay content; TN had highest weighting values (0.58), which indicated that it contributed the most to final SQI. The highest and lowest SQI values were observed for primary forest and cropland, respectively. Overall, vegetation restoration (e.g., natural restoration, artificial forests and artificial grassland) improved soil quality significantly. A GLM model explained 73.20% of the total variation in SQI, and vegetation type explained the largest proportion (46.39%) of the variation, which implies that the vegetation restoration practices can greatly enhance the soil quality in karst landscapes of southwest China. The results of this study may be used to improve implication of ecological restoration and management in degraded regions.

Advances in MS Based Strategies for Probing Ligand-Target Interactions: Focus on Soft Ionization Mass Spectrometric Techniques.

The non-covalent interactions between small drug molecules and disease-related proteins (ligand-target interactions) mediate various pharmacological processes in the treatment of different diseases. The development of the analytical methods to assess those interactions, including binding sites, binding energies, stoichiometry and association-dissociation constants, could assist in clarifying the mechanisms of action, precise treatment of targeted diseases as well as the targeted drug discovery. For the last decades, mass spectrometry (MS) has been recognized as a powerful tool to study the non-covalent interactions of the ligand-target complexes with the characteristics of high sensitivity, high-resolution, and high-throughput. Soft ionization mass spectrometry, especially the electrospray mass spectrometry (ESI-MS) and matrix assisted laser desorption ionization mass spectrometry (MALDI-MS), could achieve the complete transformation of the target analytes into the gas phase, and subsequent detection of the small drug molecules and disease-related protein complexes, and has exerted great advantages for studying the drug ligands-protein targets interactions, even in case of identifying active components as drug ligands from crude extracts of medicinal plants. Despite of other analytical techniques for this purpose, such as the NMR and X-ray crystallography, this review highlights the principles, research hotspots and recent applications of the soft ionization mass spectrometry and its hyphenated techniques, including hydrogen-deuterium exchange mass spectrometry (HDX-MS), chemical cross-linking mass spectrometry (CX-MS), and ion mobility spectrometry mass spectrometry (IMS-MS), in the study of the non-covalent interactions between small drug molecules and disease-related proteins.

Profiling of polyunsaturated fatty acids in human serum using off-line and on-line solid phase extraction-nano-liquid chromatography-quadrupole-time-of-flight mass spectrometry.

Polyunsaturated fatty acids (PUFAs) play a pivotal role in the biological effects, and are the potential biomarkers for some diseases. However, the structural diversity and similarity, the low concentration, and the interference of high abundant endogenous components challenge the PUFAs profiling. Herein, a novel analytical approach, off-line and on-line solid phase extraction-nano-liquid chromatography-quadrupole-time-of-flight mass spectrometry (off-line and on-line SPE-nano-LC-Q-TOF-MS), was established to monitor the PUFAs. The combination of off-line and on-line SPE removed most of impurities, and the recoveries ranged from 80.1% to 93.0% and the matrix effects were from 85.1% to 92.8%. Using this method, 51 PUFAs could be separated well and quantified with the limits of quantification between 0.006 and 2.2 pg. Finally, this developed method was applied successfully to simultaneously qualify and quantify the potential biomarkers in the allergic patients. 21 PUFAs including LTB4, 5S-, 11S-, 15S-HETE and 15S-HEPE showed significant differences. Our study indicated that the established method has the potential to sensitively and accurately determine the PUFAs in biological samples.

Spectroscopic studies of the interaction mechanisms between mono-caffeoylquinic acids and transferrin.

Transferrin (Tf) is an important protein responsible for circulating and transporting iron into cytoplasm. Tf can be taken into cells through endocytosis mediated by Tf receptor, which usually overexpresses in cancer cells. The Tf-Tf receptor pathway opens a possible avenue for novel targeted cancer therapy by utilizing Tf-binding active compounds. Among which, anti-cancer active caffeoylquinic acids (CQAs) were recently found to be promising Tf-binders by our group. For better understanding the anti-cancer activities of CQAs, it is important to unveil the binding mechanisms between CQAs and Tf. In this study, the fluorescence quenching, surface plasmon resonance (SPR), circular dichroism (CD) and molecular docking were used to investigate the interactions between CQA and Tf. The results showed that the calculated apparent association constants of interactions between 1-, 3-, 4- and 5-CQA and Tf at 298K were 7.97×105M-1, 4.36×107M-1, 6.58×105M-1 and 4.42×106M-1, respectively. The thermodynamic parameters indicated that the interaction between 1-, 3-, 5-CQA and Tf is due to H-bonding, and electrostatic interactions were likely involved in the binding of 4-CQA and Tf. The CD results indicated that bindings of 1-CQA, 4-CQA and 5-CQA with Tf resulted in more stretched ß-turn and random coil translated from ß-sheet. In contrast, 3-CQA led to more stable a-helix conformation. Molecular docking studies of CQAs with Tf further displayed that CQAs were able to interact with residues near Fe3+ binding site. The spectroscopic studies revealed the action mechanisms, thermodynamics and interacting forces between CQAs and Tf, and thus are helpful for future design and discovery of Tf-binders for targeted cancer therapy applying Tf-Tf receptor pathway.

Development of propidium iodide as a fluorescence probe for the on-line screening of non-specific DNA-intercalators in Fufang Banbianlian Injection.

Fufang Banbianlian Injection (FBI) has been widely used as an anti-inflammatory and anti-tumor prescription. To understand the relationships between its bioactive ingredients and pharmacological efficacies, our previous study has been successfully identified some DNA-binding compounds in FBI using an established on-line screening system, in which 4',6-diamidino-2-phenylindole (DAPI) was developed as a probe. However, DAPI can be only used to screen ATT-specific DNA minor groove binders, leaving the potential active intercalators unknown in FBI. As a continuation of our studies on FBI, here we present a sensitive analytical method for rapid identification and evaluation of DNA-intercalators using propidium iodide (PI) as a fluorescent probe. We have firstly established the technique of high-performance liquid chromatography-diode-array detector-multistage mass spectrometry-deoxyribonucleic acid-propidium iodide-fluorescence detector (HPLC-DAD-MS(n)-DNA-PI-FLD) system. As a result, 38 of 58 previously identified compounds in FBI were DNA-intercalation active. Interestingly, all previously reported DNA-binders also showed intercalative activities, suggesting they are dual-mode DNA-binders. Quantitative study showed that flavonoid glycosides and chlorogenic acids were the main active compounds in FBI, and displayed similar DNA-binding ability using either DAPI or PI. In addition, 13 active compounds were used to establish the structure-activity relationships. In this study, PI was developed into an on-line method for identifying DNA-intercalators for the first time, and thus it will be a useful high-throughput screening technique for other related samples.

Rapid screening of transferrin-binders in the flowers of Bauhinia blakeana Dunn by on-line high-performance liquid chromatography-diode-array detector-electrospray ionization-ion-trap-time-of-flight-mass spectrometry-transferrin-fluorescence detection system.

Transferrin (Transferrin, TRF, TF) has drawn increasing attention in cancer therapy due to its potential applications in drug delivery. TF receptor, highly expressed in tumor cells, recognizes and transports Fe(3+)-TF into cells to release iron into cytoplasm. Thus, discovering TF-binding compounds has become an active research area and is of great importance for target therapy. In this study, an on-line analysis method was established for screening TF-binding compounds from the flowers of Bauhinia blakeana Dunn using a high-performance liquid chromatography-diode-array detector-multi-stage mass spectrometry-transferrin-fluorescence detector (HPLC-DAD-MS(n)-TF-FLD) method. As a result, 33 of 80 identified or tentatively characterized compounds in the sample were TF-binding active. Twenty-five flavonol glycosides and eight phenolic acids were identified as TF-binders. Twelve of these active compounds together with six standard compounds were used to study the dose-response effects and structure-activity relationships of flavonoids and phenolic acids. The method was validated by vitexin with a good linearity in the range of concentrations used in the study. The limit of detection for vitexin was 0.1596 nmol. Our study indicated that the established method is simple, rapid and sensitive for screening TF-binding active compounds in the extract of Bauhinia blakeana Dunn, and therefore is important for discovering potential anti-cancer ingredients from complex samples for TF related drug delivery.