Aromatic Alcohol-Based pH-Sensitive Chromophore with a Unique Near-Infrared Dual-Band Solvatochromic Property and Its Application as a Ratiometric Fluorescent Sensor for G-Quadruplexes.

Solvatochromes have gained great attention because of their unique roles in monitoring biomolecular location, interaction, and dynamics. Particularly, solvatochromes presenting both red-shifting excitation and dual-band switchable emission are in great demand yet significantly difficult to come true. In this article, we disclose an aromatic alcohol-based pH-sensitive chromophore NIR-HBT that not only presents red-shifting excitation and solvent-dependent dual-band emission but also shows high photostability and excellent brightness. To the best of our knowledge, this is the first solvatochrome to simultaneously display these optical properties. Especially, in contrast to the reported dual-band solvatochromes whose solvatochromism is achieved by affecting their excited state behaviors, the solvatochromism of NIR-HBT is realized by modulating its ground state proton dissociation, which is a new solvatochromic mechanism that has not been reported. Furthermore, based on the dual-band solvatochromism of NIR-HBT and its intrinsic binding ability to GQs, near-infrared ratiometric detection of GQs is achieved. These results indicate that NIR-HBT is an attractive solvatochrome that can be used to develop near-infrared ratiometric biosensors for biological research. More broadly, the discovered solvatochromic mechanism can also open new horizons for exploring the solvatochrome.

Early tirofiban versus heparin for bridging dual antiplatelet therapy in patients undergoing coronary endarterectomy combined with coronary artery bypass grafting: a multicenter randomized controlled trial protocol (the THACE-CABG trial).

BACKGROUND: For complete revascularization, patients with diffuse coronary artery disease should have a coronary endarterectomy and a coronary artery bypass graft (CE-CABG). Sadly, CE can lead to a lack of endothelium, which raises the risk of thrombotic events. Even though daily dual antiplatelet therapies (DAPT) have been shown to reduce thrombotic events, the risk of perioperative thrombotic events is high during the high-risk period after CE-CABG, and there is no consistent protocol to bridge DAPT. This trial aims to compare safety and efficacy between tirofiban and heparin as DAPT bridging strategies after CE-CABG. METHODS: In phase I, 266 patients undergoing CE-CABG will be randomly assigned to tirofiban and heparin treatment groups to compare the two treatments in terms of the primary safety endpoint, chest tube drainage in the first 24 h. If the phase I trial shows tirofiban non-inferiority, phase II will commence, in which an additional 464 patients will be randomly assigned. All 730 patients will be studied to compare major cardiovascular and cerebrovascular events (MACCEs) between the groups in the first 30 days after surgery. DISCUSSION: Given the possible benefits of tirofiban administration after CE-CABG, this trial has the potential to advance the field of adult coronary heart surgery. TRIAL REGISTRATION: chictr.org.cn, ChiCTR2200055697. Registered 6 January 2022. https://www.chictr.org.cn/com/25/showproj.aspx?proj=149451 . Current version: 20,220,620.

Trends and hotspots in familial hypercholesterolemia: A bibliometric systematic review from 2002 to 2022.

BACKGROUND: We visually assessed the research hotspots of familial hypercholesterolemia (FH) using bibliometrics and knowledge mapping in light of the research state and development trend of FH. METHODS: We employed bibliometric tools, such as CiteSpace and the alluvial generator, to illustrate the scientific accomplishments on FH by extracting pertinent literature on FH from the Web of Science Core Collection database from January 1, 2002, to December 31, 2022. RESULTS: A total of 4402 papers in total were selected for study; 29.2% of all articles globally were from the USA, followed by the Netherlands and England. The University of Amsterdam, University of Oslo, and University of Western Australia are the 3 institutions with the most publications in this area. Gerald F. Watts, Raul D. Santos, and John J. P. Kastelein wrote the majority of the pieces that were published. The New England Journal of Medicine, Circulation, and Atherosclerosis were the journals with the greatest number of papers in this field. Prevalence and genetic analysis of FH, proprotein convertase subtilisin/kexin 9 inhibitors, and inclisiran are current research hotspots for the condition. Future research in this area will be focused on gene therapy. CONCLUSIONS: FH research has shown shows a trend of ascending followed by leveling off. The prevalence and diagnosis of FH, proprotein convertase subtilisin/kexin 9 inhibitors, inclisiran, and gene therapy are current research hotspots. This report may serve as a reference for current research trends.

Chinese Medicine Regulates DNA Methylation to Treat Haematological Malignancies: A New Paradigm of "State-Target Medicine".

Aberrant regulation of DNA methylation plays a crucial causative role in haematological malignancies (HMs). Targeted therapy, aiming for DNA methylation, is an effective mainstay of modern medicine; however, many issues remain to be addressed. The progress of epigenetic studies and the proposed theory of "state-target medicine" have provided conditions to form a new treatment paradigm that combines the "body state adjustment" of CM with targeted therapy. We discussed the correlation between Chinese medicine (CM) syndromes/states and DNA methylation in this paper. Additionally, the latest research findings on the intervention and regulation of DNA methylation in HMs, including the core targets, therapy status, CM compounds and active components of the Chinese materia medica were concisely summarized to establish a theoretical foundation of "state-target synchronous conditioning" pattern of integrative medicine for HMs, simultaneously leading a new perspective in clinical diagnosis and therapy.

A bibliometric analysis on the progress of myocardial bridge from 1980 to 2022.

Introduction: Although the vast majority of patients with a myocardial bridge (MB) are asymptomatic, the anomaly was found to be associated with stable or unstable angina, vasospastic angina, acute coronary syndrome, and even malignant arrhythmias and sudden cardiac death in some cases. Methods: By retrieving the relevant literature on MB from 1 January 1980 to 31 July 2022 from the Web of Science Core Collection (WoSCC) database, we used the bibliometric tools, including CiteSpace, VOS viewer, and alluvial generator, to visualize the scientific achievements on MB. Results: A total of 630 articles were included. The number of published articles was in a fluctuating growth trend. These publications came from 37 contries, led by the USA and China. The leading country on MB was the United States, the leading position among institutions was Stanford University, and the most productive researcher on MB was Jennifer A. Tremmel. After analysis, the most common keywords were myocardial bridge, mortality, coronary angiography, descending coronary artery, and sudden death. Conclusion: Our findings can aid researchers in understanding the current state of MB research and in choosing fresh lines of inquiry for forthcoming investigations. Prevalence and prognosis, mechanism atherosclerosis, hemodynamic significance, and molecular autops will likely become the focus of future research. In addition, more studies and cooperations are still needed worldwide.

DNA G-Quadruplexes as a Template To Direct Cyanine Dyes To Form H-Aggregates and Application of the Self-Assembly Entity as a New G-Quadruplexes Ligands Screening Platform.

The organization of organic chromophores to form H-/J-aggregates can result in new biomaterials with unique properties and applications. DNA-template self-assembly is one of the most attractive strategies to guide the formation of chromophore aggregates. However, the DNA templates are mainly limited to canonical nucleic acids structures [single (ss)- and double (ds)-stranded DNA]. DNA G-quadruplexes (GQs), with distinct and various structural features, were rarely exploited to guide the formation of dye aggregates. In this study, we present the spontaneous assembly of cyanine dye IR786 to form H-aggregates on DNA GQs exclusively, but no IR786 aggregates formed by adjusting the experimental parameters or on ss-/ds-DNA. Furthermore, on the basis of the assembly entity (GQs-IR786), an adaptive GQs-FID (fluorescence intercalator displacement) assay for screening of GQs ligands was developed. In contrast with the existing GQs-FID screening schemes, this assay displayed attractive performance in many aspects (such as turn-on signal output, broad screening range, and time saving). All these results have undoubtedly demonstrated the great values of DNA GQs as a template to guide the formation of dye aggregates. We hope that more GQs structures would be exploited as templates to expand the variety of functional materials in the future. Moreover, the specifically formed H-aggregates of IR786 on GQs are significant for GQs' detection, and we also expect that this GQs-FID assay would be further studied and finally applied to screen GQs ligands in a high-throughput manner in the future.

Polymeric Micelles Encapsulating a Small Molecule SO2 Fluorescent Probe Exhibiting Novel Analytical Performance and Enhanced Cellular Imaging Ability.

Because of the limited knowledge on the relationship between molecular structure and analytical performance, developing a small molecule fluorescent probe with desirable response properties is usually a laborious work. On the other hand, the application of small molecule fluorescent probe in biological samples is always limited due to the unwanted interaction between dyes and biomacromolecules. Polymer micelles, thanks to its unique core-shell structure, may have the potential to improve these situations. However, utilization of polymer micelles to improve these situations is rarely explored. Herein, we engineered the first micellar SO2 nanoprobe Nano-Cz by self-assembly of a carbazole-based SO2 small molecule probe and an amphiphilic copolymer (DSPE-mPEG2000). The optical and cell imaging experiments revealed that Nano-Cz can work in 100% aqueous environment and act as an effective mitochondrial-targeting ratio SO2 nanoprobe. Compared with the single small molecule probe, Nano-Cz showed extraordinary large dynamic response range (0-0.7 mM vs 0-50 µM), eliminated signal interference from DNA and superior cellular imaging performance. These results clearly show the ability of polymer micelles in modulating sensors' analytical performance and reducing the signal interference from the unwanted interaction between small molecule probe and biomacromolecule, indicating that polymer micelles encapsulating single small molecule probe can provide us an alternative strategy to explore sensors with various performance and promote the biological application of fluorescent sensors. In addition, we hope that more and more polymer micelles would be used to construct biosensors in the future.

[Protective effect of ß-asarone on AD rat model induced by intracerebroventricular injection of Aß1₋42 combined 2-VO and its mechanism].

This study was aimed to investigate the protective effect and mechanism of ß-asarone on the animal model of Alzheimer's disease(AD) which was induced by intracerebroventricular injection of Aß1₋42 combined cerebral ischemia. One hundred and five rats were randomly divided into seven groups including sham-operated group, AD model group, ß-asarone 10 mg•kg⁻¹ group, ß-asarone 20 mg•kg⁻¹ group, ß-asarone 30 mg•kg⁻¹ group, donepezil group(0.75 mg•kg⁻¹) and Ginkgo biloba extract group(24 mg•kg⁻¹). Rats' learning and memory abilities, cerebric regional blood flow, pathological changes in hippocampal CA1 region, the expression level of HIF-1α and serum CAT, SOD and MDA level were detected 4 weeks later. The results showed that the application of intracerebroventricular injection of Aß1₋42 joint 2-VO could lead to rats' dysfunction of learning and memory, decrease in regional cerebral blood flow. Neurons in CA1 region were arranged in disorder, and amyloid deposition was increased. The number of cerebral cortical cells expressing HIF-1α was increased as well. The level of serum CAT and SOD decreased, while level of serum MDA increased. However these symptoms were improved by 20 mg•kg⁻¹ and 30 mg•kg⁻¹ ß-asarone. The results indicated that ß-asarone could effectively relieve the symptoms of the AD model induced by intracerebroventricular injection of Aß1₋42 combined cerebral ischemia, and the potential mechanism might be that it could attenuate damage of MDA to the body by improving the level of CAT and SOD, meanwhile the level of HIF-1α decreased as the decline of hyperoxide which might attenuate its damage to neuron, so it finally achieved alleviating Alzheimer's disease.

Molecular engineering of a dual emission near-infrared ratiometric fluorophore for the detection of pH at the organism level.

A near-infrared ratiometric fluorophore (NIR-HBT) was rationally designed and constructed by expanding both the excitation and emission wavelength of the classical ratiometric fluorophore 2-(benzothiazol-2-yl)phenol (HBT) into the near-infrared region. The NIR-HBT was easily synthesized by incorporating the HBT module into the hemicyanine skeleton and showed evident NIR ratiometric fluorophore characteristics. Further application of the new fluorophore for pH detection demonstrated that NIR-HBT possesses superior overall analytical performance and NIR-HBT was successfully applied for detection of acidosis caused by inflammation in living animal tissue, which indicated the potential application value of NIR-HBT in biological imaging and sensing.

[Effects of growth years of Paeonia lactiflora on bacterial community in rhizosphere soil and paeoniflorin content].

To explore the relationship between microecological environment and Paeonia lactiflora the effects of growth years of P. lactillora on rhizosphere bacterial communities were studied by PCR-DGGE and the paeoniflorin content determined by HPLC. Results showed that the soil pH increased with growing years of P. lactillora. In the fourth year, soil pH and enzyme activity reached the highest level, while organic matter content was the lowest. The bacterial diversity had a positive correlation with growing years varied from 3.38 to 3.61. Sequencing results demonstrated that Gammaproteobacteria, llphaproteobacteria, Actinobacteria, Acidobacte- ria and Firmicutes were predominant bacteria kinds in the soil of P. lactillora. Gammaproteobacteria was only detected in the bulk soil, while llphaproteobacteria, Acidobacteria G1l, Actinobacteria were only in the rhizosphere soil and the bacterial community among different growing years were similar except few species. HLPC results showed that paeoniflorin content was 3.26%, 3.30%, 3.36%, 3.41% separately from one to four-year-old P. lactiflora with an upward trend. The correlation analysis indicated that the paeoniflorin content had a positive correlation with soil pH and bacterial diversity, conversely, had a negative correlation with organic matter con- tent. During the growth years the rhizosphere bacterial diversity increased without changes of predominant bacteria and the paeoniflorin content increased without significant differences while its production increased significantly, which was different from the plants showing replanting diseases. This is in line with the farming practice choosing 4-year-old P. lactllora, but not the 1-3 year old one. In addition, the accumulation of paeoniflorin is closely related to soil pH, organic matter content and bacteria diversity, confirming that the geoherblism of P. lactiflora is closely related with microbial environment in the soil.

[Effect of different treatment on endophytic bacterial communities in continuous cropping of Chrysanthemum morifoliu].

To reveal the effect of rotation cropping and bacterial manure on the growth of Chrysanthemum morifolium and screen the beneficial endophytic, the diversity of endophytic and dominant genera of different treatment groups were analyzed. Four different treatments were continuous cropping, rotation, self-made organic fertilizer and commercially available fertilizer, respectively. Endophytic bacterial diversity and dominant genera in different organs were examined using Terminal Restriction Fragment Length Polymorphism (T-RFLP). The results showed that enzyme Hae III was more appropriate than enzyme Hinfl because the number of TRFs digested by enzyme Hae III was more than that of enzyme Hinfl. In comparison of diversity, the endophytic bacterial communities' diversity index in group of cropping rotation and fertilizer was higher than that of continuous cropping which indicated that the addition of exogenous microorganism in soil could increase the diversity of plant endophyte. 18 dominant species were selected, including 3 kinds of Firmicutes, 4 kinds of Actinomycetes and 11 kinds of Proteobacteria. The results of dominant species comparison showed that the number of dominant species in continuous cropping of Ch. morifolium was significantly less than that of the rotation group. Some dominant bacteria in rotation group and fertilizer group such as Arthrobacter, Streptomyces, Streptomyces, Flavobacterium and Mycobacterium were not found in the continuous cropping of Ch. mortfolium group. Dominant species of fertilizer treatment group was similar with the rotation group, and the continuous cropping group's dominant species was more abundant. It indicates that these bacteria may be able to mitigate hindrance in continuous cropping, especially the Flavobacterium which can decompose the pathogenic fungi is worthy of further attention. Compared with leaves, there are more dominant species in roots and stems. The diversity of edophytic bacterial communities in continuous cropping of Ch. morifolium stays below than that in the rotation of Ch. morifolium, and fertilizer treatment can increase the diversity of continuous cropping so that it could mitigate hindrance in continuous cropping.

[Differences of fungal diversity and structure in rhizosphere of Fritillaria thunbergii from different provenances].

To explore the mechanism of soil microbial ecology, the differences of fungal diversities in rhizosphere of different provenances of Fritillaria thunbergii were analyzed. The diversities and compositions of rhizo-fungi of the samples were analyzed by using DGGE and 454 pyrosequencing. DGGE results showed the Shannon index of Ninbo provenance planted in Ninbo was the highest one. And its dominant fungi were Ascomycota, Deuteromycota and Zygomycota. Except the same fungi, every provenance planted in Ninbo had its own special ones. From the 454 pyrosequencing, the fungal diversity in Panan producing was the highest which was similar with DGGE result. Among the ten phylum detected in its rhizosoil, Fungi_incertae_sedis, Ascomycota, Mucoromycotina, Basidiomycota and Chytridiomycota almost amounted to 90% of the whole community. The fungal types and amounts in Panan were more than those in Ninbo indicating the differences between producing areas and the advantage of macro genome sequencing. There were 10 phyla, 29 families, 28 genus and 159 species of fungi in Panan provenance, 6 phyla, 20 families, 19 genus, 136 species in Ninbo provenance, 8 phyla, 37 families, 47 genus, 289 species in Nantong provenance and 7 phyla, 25 families, 24 genus, 102 species in the bulk soil. Some genus such as Dothidea, Capnobotryella and Conidiobolus were only existed in Nantong provenance, while Pyrenochae- ta, Glomus and Pseudonectria were only in Panan provenance, which implied these species could grew because F. thunbergii influenced the existence of fungi. Experiments of provenance and producing area of F. thunbergii showed that the fungal diversity of indigenous provenance was higher than that of exotic provenance and each provenance had unique fungal species in the rhizosphere, which indicated that the diversity and structure was shaped cooperatively by the species and soil type. These fungal species are interacted with the soil-rhizhosphere-microbe microecological system, which in turn influence the growth of F. thunbergii.

Biodegradable cyclen-based linear and cross-linked polymers as non-viral gene vectors.

Several 1,4,7,10-tetraazacyclododecane (cyclen)-based linear (3a-c) and cross-linked (8a-d) polymers containing biodegradable ester or disulfide bonds were described. These polymeric compounds were prepared by ring-opening polymerization from various diol glycidyl ethers. The molecular weights of the title polymers were measured by GPC. Agarose gel retardation assays showed that these compounds have good DNA-binding ability and can completely retard plasmid DNA (pDNA) at weight ratio of 20 for linear polymers and 1.2 for cross-linked polymers. The degradation of these polymers was confirmed by GPC. The formed polyplexes have appropriate sizes around 400 nm and zeta-potential values about 15-40 mV. The cytotoxicities of 8 assayed by MTT are much lower than that of 25 KDa PEI. In vitro transfection toward A549 and 293 cells showed that the transfection efficiency (TE) of 8c-DNA polyplex is close to that of 25 kDa PEI at 8c/DNA weight ratio of 4. Structure-activity relationships (SAR) of these linear and cross-linked polymers were discussed in their DNA-binding, cytotoxicity, and transfection studies. In addition, in the presence of serum, the TE of 8/DNA polyplexes could be improved by introducing chloroquine or Ca(2+) to pretreated cells.