Viable Escherichia coli enumeration on a polydimethylsiloxane (PDMS) chip with vertical channel-well configuration.

The culture-based methods for viable Escherichia coli (E. coli) detection suffer from long detection time and laborious procedures, whereas the molecule tests and immune recognition technologies lack live/dead E. coli differentiation. Rapid, easy-to-use, and accessible viable E. coli detection is of benefit to bacterial infection diagnosis and risk warning of E. coli contamination of water and food, safeguarding human health. Herein, we propose a microwell chip-based solution to realize simple and rapid determination of viable E. coli. The vertical channel-well configuration is applied to develop the microwell array chip for increasing the microwell density (6200 wells/cm2), yielding a broad dynamic range from 103 to 107 CFU/mL. We incorporate an inducible enzyme assay with the developed chip and achieve the differentiation of live/dead E. coli within 4 h, significantly shortening the detection time from over 24 h in the standard method. By encapsulating single E. coli into microwells, the concentration of viable cells can be determined simultaneously through counting positive microwells. In addition, the air soluble PDMS that can store negative pressure for independent sample digitalization endows the developed chip with simple operation and less reliance on external equipment. With further developments for increasing the number of microwell and integrating more sample panels, the developed chip can become a useful tool for rapid viable E. coli enumeration with user-friendly operation, simple procedures, and accessibility in decentralized settings, thereby deploying this device for water and food safety monitoring, as well as clinical bacterial infection diagnosis.

Digital metabolic activity assay enables fast assessment of 2D materials bactericidal efficiency.

BACKGROUND: The identification and quantification of viable Escherichia coli (E. coli) are important in multiple fields including the development of antimicrobial materials, water quality, food safety and infections diagnosis. However, the standard culture-based methods of viable E. coli detection suffer from long detection times (24 h) and complex operation, leaving the unmet requirement for fast assessing the efficiency of antimicrobial materials, early alerting the contamination of water and food, and immediately treatment of infections. RESULTS: We present a digital ß-d-glucuronidase (GUS) assay in a self-priming polydimethylsiloxane (PDMS) microfluidic chip for rapid E. coli identification and quantification. The GUS expression in viable bacteria was investigated to develop a fast GUS assay at the single-cell level. Single E. coli were stochastically discretized in picoliter chambers and identified by specific GUS activity. The digital GUS assay enabled identifying E. coli within 3 h and quantifying within 4 h for different E. coli subtypes. The specificity of our method was confirmed by using blended bacteria including E. coli, Bacillus, Shigella and Vibrio. We utilized digital GUS assay to enumerate viable E. coli after incubated with antibacterial materials for assessing the antibacterial efficiency. Moreover, the degassed chip can realize automatic sample distribution without external instruments. SIGNIFICANCE: The results demonstrated the functionality and practicability of digital GUS assay for single E. coli identification and quantification. With air-tight packaging, the developed chip has the potential for on-site E. coli analysis and could be deployed for diagnosis of E. coli infections, antimicrobial susceptibility testing, and warning the fecal pollution of water. Digital GUS assay provides a paradigm, examining the activity of metabolic enzyme, for detecting the viable bacteria other than E. coli.

Relict Plants Are Better Able to Adapt to Climate Change: Evidence from Desert Shrub Communities.

Shrubs are the main dominant plants in arid desert systems and play an important role in maintaining the biodiversity, ecosystem services and stability of desert ecosystems. Studies have shown that the survival of a large number of shrub species in desert areas under the influence of climate change is significantly threatened, with different species showing different response strategies. To test the tolerance of different shrub species to climate change, this study selected 10 dominant shrub species (ancient relict shrub species and regional endemic shrub species) in the Alashan desert area as the research object. Based on a field survey of species distribution, a species distribution model was developed to simulate the suitable distribution area of shrub species under current conditions and under future climate change scenarios. The distribution changes of ancient relict and regional endemic shrub species under the climate change scenarios were tested, and the tolerance of the two types of shrub to climate change was analyzed. The results showed that under different climate change scenarios, except for Ammopiptanthus mongolicus, the total suitable area of four out of the five relict plants was relatively stable, the potential distribution area of Tetraena mongolica increased, and the future distribution pattern was basically consistent with the current distribution. However, the suitable area of typical desert plants was unstable under different climate change scenarios. Except for Kalidium foliatum, the suitable distribution areas of four out of the five shrubs showed different degrees of reduction, and the distribution location showed significant migration. Based on the research results, climate change will lead to the reduction and displacement of the distribution area of typical desert shrubs, while relict shrubs will be less affected by climate change. This is because, compared to desert species, relict plants have a longer evolutionary history and have developed a wider range of adaptations after experiencing dramatic environmental changes. This study provides a scientific basis for actively responding to the impacts of climate change on desert ecosystems.

Squeezed state in the hydrodynamic focusing regime for Escherichia coli bacteria detection.

Flow cytometry is an essential technique in single particle analysis and cell sorting for further downstream diagnosis, exhibiting high-throughput and multiplexing capabilities for many biological and biomedical applications. Although many hydrodynamic focusing-based microfluidic cytometers have been demonstrated with reduced size and cost to adapt to point-of-care settings, the operating conditions are not characterized systematically. This study presents the flow transition process in the hydrodynamic focusing mechanism when the flow rate or the Reynolds number increases. The characteristics of flow fields and mass transport were studied under various operating conditions, including flow rates and microchannel heights. A transition from the squeezed focusing state to the over-squeezed anti-focusing state in the hydrodynamic focusing regime was observed when the Reynolds number increased above 30. Parametric studies illustrated that the focusing width increased with the Reynolds number but decreased with the microchannel height in the over-squeezed state. The microfluidic cytometric analyses using microbeads and E. coli show that the recovery rate was maintained by limiting the Reynolds number to 30. The detailed analysis of the flow transition will provide new insight into microfluidic cytometric analyses with a broad range of applications in food safety, water monitoring and healthcare sectors.

Inoculum size-insensitive susceptibility determination of urine sample based on in-situ measurement of inducible enzyme activity after 20 min of antibiotic exposure.

BACKGROUND: The empirical antibiotic therapies for bacterial infections cause the emergence and propagation of multi-drug resistant bacteria, which not only impair the effectiveness of existing antibiotics but also raise healthcare costs. To reduce the empirical treatments, rapid antimicrobial susceptibility testing (AST) of causative microorganisms in clinical samples should be conducted for prescribing evidence-based antibiotics. However, most of culture-based ASTs suffer from inoculum effect and lack differentiation of target pathogen and commensals, hampering their adoption for evidence-based antibiotic prescription. Therefore, rapid ASTs which can specifically determine pathogens' susceptibilities, regardless of the bacterial load in clinical samples, are in urgent need. RESULTS: We present a pathogen-specific and inoculum size-insensitive AST to achieve the reliable susceptibility determination on Escherichia coli (E. coli) in urine samples. The developed AST is featured with an 1 h sample-to-result workflow in a filter, termed on-filter AST. The AST results can be obtained by using an inducible enzymatic assay to in-situ measure the cell response of E. coli collected from urine after 20 min of antibiotic exposure. The calculated detection limit of our AST (1.95 × 104 CFU/mL) is much lower than the diagnosis threshold of urinary tract infections. The specific expression of the inducible enzyme enables on-filter AST to correctly profile the susceptibilities of target pathogen to multi-type antibiotics without the interference from commensals. We performed the on-filter AST on 1 mL urine samples with bacterial loads varying from 105 CFU/mL to 107 CFU/mL and compared the results to that of standard method, demonstrating its insensitivity to inoculum size. SIGNIFICANCE: The developed AST is demonstrated to be of high sensitivity, specificity, and insensitive to inoculum size. With further developments for additional bacteria and clinical validation, on-filter AST is promising as a rapid and reliable surrogate of culture-based AST to promote the evidence-based prescription at the first visit and minimize the emergency of new multi-drug resistant microorganisms.

Enzymatic Antimicrobial Susceptibility Testing with Bacteria Identification in 30 min.

Rapid antimicrobial susceptibility testing (AST) with the ability of bacterial identification is urgently needed for evidence-based antibiotic prescription. Herein, we propose an enzymatic AST (enzyAST) that employs ß-d-glucuronidase as a biomarker to identify pathogens and profile phenotypic susceptibilities simultaneously. EnzyAST enables to offer binary AST results within 30 min, much faster than standard methods (>16 h). The general applicability of enzyAST was verified by testing the susceptibility of two Escherichia coli strains to three antibiotics with different action mechanisms. The pilot study also shows that the minimal inhibitory concentrations can be determined by enzyAST with the statistical analysis of enzymatic activity of the bacteria population exposed to varying antibiotic concentrations. With further development of multiple bacteria and sample treatment, enzyAST could be able to evaluate the susceptibility of pathogens in clinical samples directly to facilitate the evidence-based therapy.

National survey on the availability of oncology palliative care services at tertiary general and cancer hospitals in China.

BACKGROUND: This nationwide survey studied the level of palliative care (PC) access for Chinese patients with cancer among cancer care providers either in tertiary general hospitals or cancer hospitals in China. METHODS: Using a probability-proportionate-to-size method, we identified local tertiary general hospitals with oncology departments to match cancer hospitals at the same geographic area. A PC program leader or a designee at each hospital reported available PC services, including staffing, inpatient and outpatient services, education, and research, with most questions adapted from a previous national survey on PC. The primary outcome was availability of a PC service. RESULTS: Most responders reported that some type of PC service (possibly called "comprehensive cancer care," "pain and symptom management," or "supportive care") was available at their institution (84.3% of tertiary general hospitals, 82.8% of cancer hospitals). However, cancer hospitals were significantly more likely than tertiary general hospitals to have a PC department or specialist (34.1% vs. 15.5%, p < 0.001). The most popular services were pain consultation (> 92%), symptom management (> 77%), comprehensive care plans (~ 60%), obtaining advanced directives and do-not-resuscitate orders (~ 45%), referrals to hospice (> 32%), and psychiatric assessment (> 25%). Cancer hospitals were also more likely than tertiary general hospitals to report having inpatient beds for PC (46.3% vs. 30.5%; p = 0.010), outpatient PC clinics (28.0% vs. 16.8%; p = 0.029), educational programs (18.2% vs. 9.0%, p = 0.014), and research programs (17.2% vs. 9.3%, p < 0.001). CONCLUSIONS: Cancer hospitals are more likely to offer PC than are tertiary general hospitals in China. Our findings highlight opportunities to further increase the PC capacity in Chinese hospitals.

Numerical Study of Viscoelastic Microfluidic Particle Manipulation in a Microchannel with Asymmetrical Expansions.

Microfluidic microparticle manipulation is currently widely used in environmental, bio-chemical, and medical applications. Previously we proposed a straight microchannel with additional triangular cavity arrays to manipulate microparticles with inertial microfluidic forces, and experimentally explored the performances within different viscoelastic fluids. However, the mechanism remained poorly understood, which limited the exploration of the optimal design and standard operation strategies. In this study, we built a simple but robust numerical model to reveal the mechanisms of microparticle lateral migration in such microchannels. The numerical model was validated by our experimental results with good agreement. Furthermore, the force fields under different viscoelastic fluids and flow rates were carried out for quantitative analysis. The mechanism of microparticle lateral migration was revealed and is discussed regarding the dominant microfluidic forces, including drag force, inertial lift force, and elastic force. The findings of this study can help to better understand the different performances of microparticle migration under different fluid environments and complex boundary conditions.

An On-Chip Viscoelasticity Sensor for Biological Fluids.

There are so many non-Newtonian fluids in our daily life, such as milk, blood, cytoplasm, and mucus, most of which are viscoelastic heterogeneous liquid containing cells, inorganic ion, metabolites, and hormones. In microfluidic microparticle-manipulating applications, the target particles are practically distributed within the biological fluids like blood and urine. The viscoelasticity of biological fluid is constantly ignored for simplicity especially when the fluid is substantially diluted and contains rather complex components. However, even the fluid's ultraweak viscoelasticity actually affects the microparticle migration and may bring a completely different behavior compared with the Newtonian fluids. As a result, a robust and easy operated on-chip viscoelasticity sensor is potential and desired in many research and industrial fields, including assay sample preparation, clinical diagnostics, and on-chip sensor. In this work, we employed stable non-Newtonian fluid-polyethylene oxide (PEO) solutions with various concentrations to investigate and calibrate effects of the weak fluidic viscoelasticity on microparticle behaviors in a double-layered microfluidic channel. An analogy-based database of fluidic patterns for viscoelasticity sensing and relaxation time measurement was established. Then, we tested different biological fluids including blood plasma and fetal bovine serum and proved that they exhibited similar viscoelasticity effects to the PEO solutions with the corresponding concentration, which reached a good agreement with available results by references. The detection limitation of relaxation time can reach 1 ms. It promised a robust and integrated on-chip microfluidic viscoelasticity sensor for different biological fluids without complicated calculations.

Effects of Tai Chi on insomnia in elderly people with chronic non-specific low back pain: A study protocol for a randomized controlled trial.

Introduction: Chronic non-specific low back pain (CNLBP) is a complex condition characterized by pain, dysfunction, disturbed sleep, anxiety, and depression, all of which impair the quality of life. Previous studies showed that practicing Tai Chi had effects on chronic low back pain. However, there is a lack of evidence on its impact on sleep. The trial will evaluate the use of Tai Chi as a treatment for insomnia in elderly people with CNLBP. Methods: The study design will be a randomized, controlled, open-label trial. Participants (n = 106) will be recruited from the Hospital of Chengdu University of Traditional Chinese Medicine, Qing Yang District University for the Elderly, and Ci Tang Street Community. Participants will be randomly assigned to the Tai Chi group (n = 53) and the control group (n = 53). The Tai Chi group will undergo a Yang-style 24-form Tai Chi program for 8 weeks. The control group will have a waiting period of 8 weeks, followed by 8 weeks of Tai Chi practice. The primary outcomes of this study will be changes in sleep quality and pain intensity. Secondary outcomes of interest will include changes in the quality of pain, range of motion, physical performance, social support, and overall quality of life. Any adverse events and attendance rates will also be reported in this study. Clinical trial registration: ChiCTR2200064977.

Direct single-cell antimicrobial susceptibility testing of Escherichia coli in urine using a ready-to-use 3D microwell array chip.

Empirical antibiotic therapies are prescribed for treating uncomplicated urinary tract infections (UTIs) due to the long turnaround time of conventional antimicrobial susceptibility testing (AST), leading to the prevalence of multi-drug resistant pathogens. We present a ready-to-use 3D microwell array chip to directly conduct comprehensive AST of pathogenic agents in urine at the single-cell level. The developed device features a highly integrated 3D microwell array, offering a dynamic range from 102 to 107 CFU mL-1, and a capillary valve-based flow distributor for flow equidistribution in dispensing channels and uniform sample distribution. The chip with pre-loaded reagents and negative pressure inside only requires the user to initiate AST by loading samples (∼3 s) and can work independently. We demonstrate an accessible sample-to-result workflow, including syringe filter-based bacteria separation and rapid single-cell AST on chip, which enables us to bypass the time-consuming bacteria isolation and pre-culture, speeding up the AST in ∼3 h from 2 days of conventional methods. Moreover, the bacterial concentration and AST with minimum inhibitory concentrations can be assessed simultaneously to provide comprehensive information on infections. With further development for multiple antibiotic conditions, the Dsc-AST assay could contribute to timely prescription of targeted drugs for better patient outcomes and mitigation of the threat of drug-resistant bacteria.

All-In-One Escherichia coli Viability Assay for Multi-dimensional Detection of Uncomplicated Urinary Tract Infections.

The urinary tract infections by antibiotic-resistant bacteria have been a serious public health problem and increase the healthcare costs. The conventional technologies of diagnosis and antimicrobial susceptibility testing (AST) relying on multiple culture-based assays are time-consuming and labor-intensive and thus compel the empirical antimicrobial therapies to be prescribed, fueling the prevalence of antimicrobial resistance. Herein, we propose an all-in-one Escherichia coli viability assay in an enclosed 3D microwell array chip, termed digital ß-d-glucuronidase (GUS)-AST assay. It employs GUS, a specific metabolism-related enzyme, to convert the presence of E. coli into bright fluorescence. The random distribution of single bacteria in microwell array enables to quantify the E. coli concentrations by counting the positive microwells. We incorporate the most probable number with digital quantification to lower the limit of detection and expand the dynamic range to 7 orders. The digital GUS-AST assay is able to indicate the potency of antibiotics and determine the minimum inhibitory concentrations. A streamlined procedure of urine removal, bacterial separation, and digital GUS-AST is established to perform the direct analysis of bacteria population in urine. The sample-to-result workflow can be finished in 4.5 h with a limit of detection of 39 CFU/mL. With further development for additional pathogens and multiple antibiotic conditions, the digital GUS-AST assay could help physicians to prescribe timely targeted therapies for better patient outcomes and the minimum emergence of resistant bacteria.

Mechanism and Effects of Cellular Creep in a Microfluidic Filter.

Biomicroparticles such as proteins, bacterium, and cells are known to be viscoelastic, which significantly affects their performance in microfluidic applications. However, the exact effects and the quantitative study of cellular viscoelastic creep within different applications remain unclear. In this study, the cellular-deforming evolution within a filter unit was studied using a multiphysics numerical model. A general cellular creep deformation process of viscoelastic particle trapping in pores was revealed. Two featured variables, namely, the maximum surface displacement and the volumetric strain, were identified and determined to quantitatively describe the evolution. The effects of flow conditions and physical characteristics of the microparticles were studied. Furthermore, a Giardia concentration experiment was conducted using an integrated hydraulic filtration system with a porous membrane. The experimental results agreed well with the numerical analysis, indicating that, compared to pure elastic particles, it is more difficult to release cellular material matters including cells, chemical synthetic particles, and microbes from trapping due to their time-accumulated creep deformation.

Single Escherichia coli bacteria detection using a chemiluminescence digital microwell array chip.

Rapid and sensitive Escherichia coli (E. coli) detection is important in determining environmental contamination, food contamination, as well as bacterial infection. Conventional methods based on bacterial culture suffer from long testing time (24 h), whereas novel nucleic acid-based and immunolabelling approaches are hindered by complicated operation, the need of complex and costly equipment, and the lack of differentiation of live and dead bacteria. Herein, we propose a chemiluminescence digital microwell array chip based on the hydrolysis of 6-Chloro-4-methylumbelliferyl-ß-D-glucuronide by the ß-D-glucuronidase in E. coli to achieve fast single bacterial fluorescence detection. Taking the advantage of the picoliter microwells, single bacteria are digitally encapsulated in these microwells, thus the accurate quantification of E. coli can be realized by counting the number of positive microwells. We also show that the chemiluminescence digital microwell array chip is not affected by the turbidity of the test samples as well as the temperature. Most importantly, our method can differentiate live and dead bacteria through bacterial proliferation and enzyme expression, which is confirmed by detecting E. coli after pH and chlorination treatment. By comparing with the standard method of plate counting, our method has comparable performance but significantly reduces the testing time from over 24 h-2 h and 4 h for qualitative and quantitative analysis, respectively. In addition, the microfluidic chip is portable and easy to operate without external pump, which is promising as a rapid and on-site platform for single E. coli analysis in water and food monitoring, as well as infection diagnosis.

Research on Bayer Red Mud Slurry Electrolysis.

The Bayer red mud is the solid waste generated during the production of alumina by the Bayer process. At present, the stock of red mud in China exceeds 1.1 billion tons, covering an area of more than 120,000 mu, and the annual production volume is increasing by 100 million tons. The comprehensive utilization of red mud is still a difficult problem. Therefore, it is of great significance to actively explore new methods for removing sodium from red mud. In this study, the traditional red mud desalination process and the slurry electrolysis process are combined, and the influence of three different leaching agents on the leaching and sodium removal of red mud slurry in the presence of an electric field is explored. In the slurry electrolysis experiment, it was found that the sodium removal rate obtained by different leaching agents was CaO > CaCl2 > HCl. The red mud leached with pure dilute hydrochloric acid has the highest Na removal rate, which is 93.11%. In view of this situation, a pre-slurry-electrolysis cycle process with HCl as leaching agent was proposed. The core of slurry electrolysis is electrolyzing NaCl solution, and HCl only participates in the process as circulating medium. The design of this process reduces cost and increases efficiency.

[Influence of species interaction on species distribution simulation and modeling methods.] / 种间作用对物种分布模拟的影响及建模方法.

The species distribution models (SDMs) simulate and predict the potential distribution of species in geographical space by quantifying the relationships between species distribution and environmental variables, and extrapolating these relationships to unknown landscape units, which makes them important tools in ecology, biogeo-graphy, and conservation biology. Current SDMs mainly take abiotic factors as prediction variables, whereas biotic factors, especially species interactions, are often ignored due to the difficulties in data quantification and modeling. Incorporating species interactions into SDMs is considered as the main challenge of SDMs. We reviewed the influence of species interactions on species distribution simulations, clarified the necessity of incorporating species interactions into SDMs, summarized four main ways to incorporate species interactions into SDMs, analyzed their strengths and limitations, and discussed the future development direction of incorporating species interactions into SDMs. The study showed that incorporating species interaction into SDMs was based on the premise that the spatial scale of species distribution simulation was consistent with that of species interactions, and that the training data should be collected from large environmental heterogeneous space to ensure the diversity of species interactions in heterogeneous habitats. In order to eliminate the influence of multicollinearity on the prediction of SDMs, all abiotic and biotic factors should be fully considered and accurately quantified. Modeling the complex population/community dynamics would be an important development direction of incorporating species interactions into SDMs.

Molecular Mechanism of Gleditsiae Spina for the Treatment of High-Grade Serous Ovarian Cancer Based on Network Pharmacology and Pharmacological Experiments.

Background: Gleditsiae Spina, widely used in traditional Chinese medicine, has a good curative effect on malignant tumors such as ovarian cancer, but the mechanism is not clear. So, we aimed to analyze the pharmacological mechanism of Gleditsiae Spina in the treatment of high-grade serous ovarian cancer (HGSC) based on network pharmacology and biological experiments. Methods: The main active ingredients of Gleditsiae Spina were identified by high performance liquid chromatography (HPLC) and mass spectrometry (MS), and the active ingredients were performed by ADME screening. The component targets of Gleditsiae Spina were screened using the PharmMapper platform, and differentially expressed genes in normal and HGSC tissues were identified through the GEO database. Thereafter, the network of "active ingredient-targets" was constructed by cytoscape 3.7.2 software. The protein-protein interaction network was established by the BioGenet database to mine the potential protein function. Biological processes and pathways were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The binding ability of the core components of the Gleditsiae Spina and the core target of HGSC was verified by molecular docking and molecular dynamics simulation, and the therapeutic effect of Gleditsiae Spina was proved in vitro through cytotoxicity experiments. The effect of Gleditsiae Spina on the core pathway is obtained by western blotting. Results: Gleditsiae Spina had cytotoxicity on HGSC based on network pharmacology and biological experiments. Luteolin, genistein, D-(+)-tryptophan, ursolic acid, and berberine are the identified core active ingredients of Gleditsiae Spina for regulating HGSC, with HPSE, PI3KCA, AKT1, and CTNNB1as the ideal targets. The prediction results were verified by molecular docking, molecular dynamic simulation, cell viability, and western blot analysis. Conclusion: Gleditsiae Spina mainly downregulates the expression of heparanase and ß-catenin to affect the composition of tumor cytoplasmic matrix and can regulate the PI3K-AKT pathway, integrating multiple targets and multiple pathways to play a therapeutic role. It also provides a theoretical basis for the prevention of ovarian cancer and its treatment using traditional Chinese medicine in the future.

Facile Method for Preparing Hierarchical Al2O3-Glass Foam Ceramics with Superior Thermal Insulating Property.

Porous ceramics are good candidates for thermal-insulating materials. Glass is a low-cost material that possesses low intrinsic thermal conductivity of less than 10 W·m-1·K-1. However, the mechanical strength of a homogeneous glass material is fairly low. We, in this work, have fabricated Al2O3-hollow glass sphere (HGS) foam ceramics with a facile particle-stabilized foaming method. The obtained foam ceramic presents a hierarchical microstructure that is rare to be seen elsewhere using this foaming technique. The foaming system contains two types of particles having opposite charges, and the particle-stabilized foaming mechanism is hence discussed. The optimal sample possesses a porosity above 94% with a thermal conductivity as low as 0.0244 W/m·K, which reaches the level of superinsulating materials. The compressive strengths of the foam ceramics range from 0.07 to 0.83 MPa. The effective medium theory model is used to calculate the thermal conductivities as reference. The deviation of the theoretical values from the experimental ones are derived from the effect of the hierarchical microstructure of the foams. The results of this work may deepen one's understanding and pave new ways for the particle-stabilized foaming technique. The unique microstructure of the ceramic may also shed some light on fabricating superior thermal-insulating ceramic materials.

Improving the fluorescence brightness of distyryl Bodipys by inhibiting the twisted intramolecular charge transfer excited state.

A new class of NIR distyryl Bodipy fluorescent dyes were developed with sulfone- and quaternary ammonium-modified piperidines as auxochromes instead of conventional dialkylamino auxochromes. Such modification markedly improved the fluorescence quantum yields due to the efficient inhibition of the twisted intramolecular charge transfer (TICT) state. Based on the dye platform, we developed a new fluorescent H2O2 probe via self-immolative chemistry, and confirmed its capability to sensitively and selectively sense H2O2in vitro and in vivo.

Study on Medication Rules of Traditional Chinese Medicine against Antineoplastic Drug-Induced Cardiotoxicity Based on Network Pharmacology and Data Mining.

METHODS: The targets of antineoplastic drugs with cardiotoxicity were obtained from the National Center for Biotechnology Information (NCBI) database, China national knowledge infrastructure (CNKI) database, and Swiss Target Prediction platform. Then, the cardiotoxicity-related targets were derived from the Gene Cards, Disgenet, OMIM, and DrugBank databases, as well as the drug of current clinical guidelines. The targets both in these two sets were regarded as potential targets to alleviate ADIC. Then, candidate compounds and herbs were matched via Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. Cytoscape3.7.1 was used to set up the target-compound-herb network. Molecular docking between core targets and compounds was performed with AutodockVina1.1.2. The rules of herbs were summarized by analyzing their property, flavor, and channel tropism. RESULTS: Twenty-one potential targets, 332 candidate compounds, and 400 kinds of herbs were obtained. Five core targets including potassium voltage-gated channel subfamily H member 2 (KCNH2), cyclin-dependent kinase 1 (CDK1), matrix metalloproteinase 2 (MMP2), mitogen-activated protein kinase1 (MAPK1), and tumor protein p53 (TP53) and 29 core compounds (beta-sitosterol, quercetin, kaempferol, etc.) were collected. Five core herbs (Yanhusuo, Gouteng, Huangbai, Lianqiao, and Gancao) were identified. Also, the TCM against ADIC were mainly bitter and acrid in taste, warm in property, and distributed to the liver and lung meridians. CONCLUSION: TCM against ADIC has great potential. Our study provides a new method and ideas for clinical applications of integrated Chinese and western medicine in treating ADIC.