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SCA36 is a neurodegenerative disease mainly caused by the abnormal expansion of the GGGCCT repeat sequence in intron 1 of NOP56. The RNA sequences of this gene are expected to form large amounts of G-quadruplexes in the cytoplasm, which may be a potential intervention and detection target for SCA36. Here, we have developed a small-molecular compound named TCB-1, which shows good selectivity to the G-quadruplex structure, and its fluorescence can be enhanced by hundreds of folds. Interestingly, TCB-1 can avoid lysosome capture, evenly disperse in the cytoplasm, and selectively light up the cytoplasmic RNA G-quadruplexes. This property allows TCB-1 to sensitively detect the increased formation of cytoplasmic RNA G-quadruplexes in SCA36 model cells. This work not only provides new ideas for the design of small-molecule compounds targeting RNA G-quadruplexes in living cells, but also intuitively demonstrates the increased formation of RNA G-quadruplexes caused by NOP56 gene mutation, providing a possible tool for the detection of SCA36.

An organic compound can highly target the mitochondria of living cells and light up the G-quadruplex structure in the mitochondria with high specificity.

Antibiotic abuse is considered a serious problem affecting human health, necessitating that great attention be paid to explore robust, simple and sensitive methods for rapid evaluation. In this paper, we developed a fluorescent aptasensor for visual and real-time kanamycin detection by taking advantage of the label-free strategy based on H-aggregate disassembly of a chiral cyanine dye induced by a G-quadruplex aptamer. The good sensitivity and selectivity enabled this aptasensor to have a detection limit as low as 43 nM and have high specificity for kanamycin recognition. Furthermore, this assay was successfully applied for the detection of kanamycin in lake water and urine with excellent recoveries.

Noncanonical nucleic acid structures, such as G-quadruplex (G4) and i-Motif (iM), have attracted increasing research interests because of their unique structural and binding properties, as well as their important biological activities. To date, thousands of small molecules that bind to varying G4/iM structures have been designed, synthesized and tested for diverse chemical and biological uses. Because of the huge potential and increasing research interests on G4-targeting ligands, we launched the first G4 ligand database G4LDB in 2013. Here, we report a new version, termed G4LDB 2.2 (http://www.g4ldb.com), with upgrades in both content and function. Currently, G4LDB2.2 contains >3200 G4/iM ligands, ∼28 500 activity entries and 79 G4–ligand docking models. In addition to G4 ligand library, we have also added a brand new iM ligand library to G4LDB 2.2, providing a comprehensive view of quadruplex nucleic acids. To further enhance user experience, we have also redesigned the user interface and optimized the database structure and retrieval mechanism. With these improvements, we anticipate that G4LDB 2.2 will serve as a comprehensive resource and useful research toolkit for researchers across wide scientific communities and accelerate discovering and validating better binders and drug candidates.

BACKGROUND: Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), have fever, dry cough, dyspnea, and fatigue. The disease has now become a global pandemic. The purpose of this study was to explore the relationship between COVID-19 and gastrointestinal (GI) symptoms. METHODS: We collected and analyzed data on patients with laboratory-confirmed COVID-19 by high-throughput sequencing or reverse transcription-polymerase chain reaction. We reviewed electronic medical records of 405 hospitalized COVID-19 patients in the Third Hospital of Wuhan. RESULTS: Among the 405 confirmed patients, 210 had no GI symptoms, 195 had GI symptoms, and the first symptom of 155 patients was GI. The prevalence of vascular and digestive diseases in the group with GI symptoms was significantly higher than in the group without GI symptoms. In patients with GI symptoms, the proportion with fever, cough, dysphoria, chest tightness, poor appetite, chest pain, and pharyngeal pain was significantly higher than in those without GI symptoms. There was no significant difference in imaging between the 2 groups. In patients with GI symptoms, the proportion with increased procalcitonin (PCT) level and decreased lymphocyte count was significantly higher than in those without GI symptoms. CONCLUSION: COVID-19 patients with GI symptoms had significantly more vascular and digestive system diseases and were more likely to have clinical manifestations of fever, cough, poor appetite, chest tightness, chest pain, insomnia, and pharyngeal pain. There were more patients with diarrhea, nausea, and vomiting. Patients with GI symptoms were more likely to have increased PCT and decreased lymphocyte count.

Background: Hyperglycemia is common in Intensive Care Unit (ICU) and was reported with high mortality and adverse patients’ outcomes. The infection of COVID-19 is identified as a main source of increase in the incidence of hyperglycemia and associated elevated mortality. In order to reduce the healthcare providers exposure and the personal protective equipment use during the pandemic, the US Food and Drug Administration (FDA) regulated the usage of continuous glucose monitoring (CGM) devices to address these concerns as well as control the glucose level at a desired range. What are the benefits of using CGM applications? The article updates knowledge on this topic. Methods：We did our search on the following databases: MEDLINE, EMBASE and Cochrane database, articles included were all recent and between January 2020 to July 2022. Our main focus was on articles with evidence concerning the effectiveness and the accuracy of continuous blood glucose monitoring methods in ICU during the COVID-19 pandemic. Results: A few recent articles were identified and scrutinized. These allow the article to present an overview of the most recent international evidence on the topic, ts benefits and a comparison between methods and devices. Main Contribution to Evidence-Based Practice: The article puts together the most recent evidence on the demonstrated benefits of continuous glucose monitoring and identifies the few glucose Monitoring Devices about which there is recent published scientific evidence on its application to critical care.

A fluorescent light-up ligand for an i-motif structure has been reported in this study. Chelerythrine (CHE) could bind to i-motif and show a significant increase in the fluorescence intensity, while exhibiting weak response towards single-stranded (ssDNA), double-stranded (dsDNA), and G-quadruplexes. This feature makes CHE advantageous in the label-free fluorescence sensing systems.

Acute lymphoblastic leukemia (ALL) is one of the common malignant tumors. Compared with childhood ALL, the treatment effect of adult B-cell ALL is less effective and remains a big challenge. In order to explore the pathogenesis of adult B-cell ALL and find new diagnostic biomarkers to develop sensitive diagnostic tools, we investigated the plasma metabolites of adult B-cell ALL by using 1H NMR (nuclear magnetic resonance) metabolomics. Relative to healthy controls, adult B-cell ALL patients showed abnormal metabolism, including glycolysis, gluconeogenesis, amino acid metabolism, fatty acid metabolism and choline phospholipid metabolism. What's more important, we also found that the optimal combination of choline, tyrosine and unsaturated lipids has the potential to diagnose and prognose adult B-cell ALL in the clinic.

Emerging studies have shown that mitochondrial G-quadruplex plays a critical role in regulating mitochondrial gene replication and transcription, which makes it a promising target for the diagnosis and treatment of cancer or other major diseases. Molecular compounds that can highly target the mitochondrial G-quadruplexes in live cells are essential for further revealing the function and mechanism of these G-quadruplexes. Here, we have developed an organic molecular compound that can highly target the mitochondria of living cells by virtue of the membrane potential mechanism. Then it shows high selectivity to the G-quadruplex structure in the mitochondria, and its fluorescence overlaps well with that of the BG4 antibody. Moreover, the compound has extremely low cytotoxicity and does not interfere with the natural state of G-quadruplex structure. With these good properties, this compound will have great potential in mitochondrial G-quadruplex tracking research or targeted drug screening.

Herein, we carried out the supramolecular self-assembly of cyanine dye (MTC) for the transformation between duplex DNA and G-quadruplex (T30695) for the highly selective and sensitive recognition of Pb2+ ions via UV-vis spectroscopy. A specific duplex DNA (duplex-a) consisting of a Pb2+ aptamer and its part complementary strand was constructed, which could be unwound to single-strand DNA to form a G-quadruplex in the presence of Pb2+. The formed G-quadruplex could transform MTC H-aggregates into monomers, resulting in a specific recognition absorption signal.

G-quadruplex (G4) is a four-stranded DNA structure, which is commonly over-represented in gene promoter regions and viewed as an emerging therapeutic target in oncology, as the transcriptional repression of oncogenes through the stabilization of the G4 structure could be a novel anticancer strategy. Traditional Chinese Medicine (TCM), whose agents have diversity in structure and bioactivity, provides an abundant source of G4 ligands. Herein, we present a G4 functionalized magnetic system for screening potential anticancer compounds from TCM. In this system, magnetic microbeads were functionalized with G4 DNA that served as signal molecular nanocarriers. The results showed that the method was able to screen out the targeted molecule(s) with high G4-affinity from the mixture. With the thus established system, several protoberberine alkaloids, the G4 ligands, were successfully screened out from two TCMs, namely, Rhizoma Coptidis and Cortex Phellodendri Chinensis. Compared with the reported screening systems, the G4 functionalized magnetic system developed in this work is simple and easy-to-operate, and can screen out G4-specific binding agents with high specificity and high sensitivity. The method will prospectively promote the discovery of novel active therapeutic drugs or diagnostic probes in the future.

A highly selective and sensitive direct detection of potassium (K+) and lead (Pb2+) ions was developed by using the assembly and disassembly of a chiral cyanine dye/TBA complex. The dye DMSB (3-ethyl-2-[3-(3-ethyl-3H-benzoselenazol-2-ylidene)-2-methylprop-1-enyl] benzoselenazolium bromide) loses the ability of self-assembly, but it can be activated by thrombin-binding aptamer (TBA) G-quadruplex structure. And only the TBA G-quadruplex formed in the presence of K+, can strongly induce J-aggregate signals of DMSB. Because the Pb2+ ions can bind and stabilize the TBA G-quadruplex with much higher efficiency than K+, the J-aggregate signals of DMSB falls sharply when the Pb2+ is present. As a result, the assembly and disassembly of DMSB allows the selective detection of 10 μM K+ and 20 nM Pb2+ respectively, even the competitive sodium ion (Na+) was as high as 145 mM. The linear correlation existed between the J-aggregate intensity and the concentration of K+ and Pb2+ over the range of 0.5–5.0 mM and 200–2000 nM, respectively. Moreover, the concentration of K+ (∼3 mM) and Pb2+ (below 20 nM) in human blood serum samples were determined by the present method, which agreed well with inductively coupled plasma mass spectrometry (ICP-MS). This work not only opens a door for the further development of G-quadruplex-based aptasensor in complex real system, but also provides a simple and versatile sensing platform for ion detection in clinic.

Filamentous bacteria, particularly Microthrix parvicella, are mainly responsible for bulking or foaming of activated sludge. Based on the affinity of M. parvicella to the hydrophobic characteristics of long-chain fatty acids, a novel bisoctyl rhodamine B (BORB) and a novel fluorescence resonance energy transfer (FRET) complex probe were prepared herein to study their properties. When the FRET probe was used in in situ activated sludge, M. parvicella was clearly labeled at 20 nmol/L, which was a reduction of 50 times compared to that of the BORB (1 μmol/L) alone and 500 times compared to the carbazole–quinoline probe reported previously. Compared with fluorescence in situ hybridization, M. parvicella could be clearly labeled using BORB and the FRET probe in situ without requiring complicated pretreatments (i.e., shock and broken process, fixed sample, digestion, and lysozyme treatment). This study discusses the facile approach developed for labeling M. parvicella in early warning expansion, thereby inhibiting and controlling sludge bulking in situ.

Cyanine dyes have attracted more and more interest due to their controllable assembly and disassembly process with biomolecular templates. The self-assembly of cyanine dye not only depend on the environment, but also on their structures. Here, we report assembly and disassembly of two cyanine dyes, a dimeric cyaine dye (TC-P4) and its corresponding monomer (TC). In PBS, these dyes could form aggregates. The parallel c-myc G-quadruplex as a template causes the transformation of TC-P4 from H-aggregates to dimer and monomer; while duplex and single-stranded DNAs could not. The interaction between these DNAs motifs and TC could all induce the appearance of monomer band. Parallel c-myc G-quadruplex could enhance the fluorescence intensity of TC-P4 and TC. The self-assembly and disassembly of TC and TC-P4 could be regulated and used as probes for G-quadruplex recognition from duplex and single-stranded DNAs in solution.

Glutaminase 1 (GLS1) has recently been reported to be expressed in microglia and plays a crucial role in neuroinflamation. Significantly increased level of GLS1 mRNA expression together with neuroinflammation pathway were observed in postmortem prefrontal cortex from depressed patients. To find out the function of microglial GLS1 in depression and neuroinflammation, we generated transgenic mice (GLS1 cKO), postnatally losing GLS1 in microglia, to detect changes in the lipopolysaccharide (LPS)-induced depression model. LPS-induced anxiety/depression-like behavior was attenuated in GLS1 cKO mice, paralleled by a significant reduction in pro-inflammatory cytokines and an abnormal microglia morphological phenotype in the prefrontal cortex. Reduced neuroinflammation by GLS1 deficient microglia was a result of less reactive astrocytes, as GLS1 deficiency enhanced miR-666-3p and miR-7115-3p levels in extracellular vesicles released from microglia, thus suppressing astrocyte activation via inhibiting Serpina3n expression. Together, our data reveal a novel mechanism of GLS1 in neuroinflammation and targeting GLS1 in microglia may be a novel strategy to alleviate neuroinflammation-related depression and other disease.

Acute myeloid leukemia (AML) is a common acute leukemia in both adults and children, with poor early detection and diagnosis. Therefore, identifying new indicators for AML detection is significant for effective treatment. Here, we developed a supramolecular probe that exhibits high specificity and sensitivity to G-quadruplex structures in physiological buffer solution, chromosomes, and cells. Using this probe, we tested the DNA extracted from different types of cells and found that the DNA extracted from human acute myeloid leukemia cells HL-60 and KG-1 enhanced the probe fluorescence more significantly than the DNA extracted from other cells. This phenomenon may be related to a large number of G-quadruplexes in acute myeloid leukemia cells, implicating that G-quadruplex levels may be a potential indicator for the detection of acute myeloid leukemia.

Mitochondria autophagy, also known as mitophagy, is a process in which mitochondria are wrapped by autophagosomes and fused with lysosomes for degradation. This process is essential for mitochondrial quality control. Here, we developed a hybrid aggregate FRET probe through mixed assembly of two cyanine dyes FMOTY and AMTC. In live cells, FMOTY and AMTC exist independently in lysosomes and mitochondria and will not produce interfering FRET background signals. The FRET signal is only generated when mitochondria is transported to lysosomes during mitophagy. This allows the hybridized aggregate to be used as a highly specific probe for monitoring mitophagy.

The G-quadruplex structure formed by the c-myc gene sequence has attracted much attention due to its important physiological function in biology and wide application in nanotechnology. So far, probes capable of recognition of c-myc G-quadruplex with both high specificity and sensitivity are still scarce. This work presented a cyanine dye fluorescent probe named Cy-1, which has almost no fluorescence in aqueous solution, but showing more than 1000-fold fluorescence enhancement for recognizing c-myc G-quadruplex. Cy-1 also has good specificity and can selectively recognize c-myc G-quadruplex from other a variety of G-quadruplex and non-G-quadruplex structures. These properties make Cy-1 a promising probe for c-myc G-quadruplex recognition in nanotechnology or biology.

Endothelial injuries, including cell pyroptosis, are ongoing inflammatory processes with key roles in atherosclerosis development. Our previous report showed that the chemokine CXCL12 and its receptor CXCR7 are associated with the proliferation and angiogenesis of endothelial cells. Nevertheless, the mechanism underlying these effects on atherosclerotic lesions, especially on endothelial dysfunction, remains unknown. Here, we demonstrated that CXCR7 was upregulated in human carotid atherosclerotic plaques, apolipoprotein E knockout (ApoE−/−) mice fed with a high‐fat diet (HFD), and oxidized lipopolysaccharide‐treated (ox‐LDL) human umbilical vein endothelial cells (HUVECs). Further, the activation of CXCR7 reversed ox‐LDL‐induced HUVEC dysfunction, such as migration, tube formation, and cell pyroptosis; all of these protective effects were alleviated by inhibition of CXCR7. The NOD‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasomes were also elevated in human carotid atherosclerotic plaques, ApoE−/− mice fed with HFD, and ox‐LDL‐injured HUVECs by regulation of caspase‐1 and interleukin (IL)‐1β expression. The activation of CXCR7 by TC14012 led to a decrease in atherosclerotic lesions in ApoE−/− mice fed with HFD. TC14012 also inhibited the expression of the NLRP3 inflammasome signaling pathway in vivo. In conclusion, our study suggests that CXCR7 plays an important role in regulating NLRP3 inflammasome‐modulated pyroptosis in HUVECs, providing a potential novel therapy for atherosclerosis., CXCR7 is upregulated in human carotid plaque tissues, HFD‐treated ApoE−/− mouse aortas, and ox‐LDL‐treated HUVECs. Activation of CXCR7 alleviates ox‐LDL‐induced endothelial injury and cell pyroptosis. Activation of CXCR7 reduces atherosclerosis progression by mitigating the pyroptosis pathway in vivo.

Development of a cysteine (Cys) detection probe is of significant importance in clinical diagnosis. Herein, a colorimetric, chiral and fluorometric multi-approach detection probe for Cys has been designed. This probe utilized G-quadruplexes as a template to regulate the supramolecular transformation of a cyanine dye and achieve label-free and highly selective detection of Cys. Its successful use in urinary Cys measurement demonstrates good promise for practical applications.

Background G-quadruplex has been viewed as a promising therapeutic target in oncology due to its potentially important roles in physiological and pathological processes. Emerging evidence suggests that the biological functions of G-quadruplexes are closely related to the binding of some proteins. Insulin-like growth factor type I (IGF-1), as a significant modulator of cell growth and development, may serve as a quadruplex-binding protein. Methods The binding affinity and selectivity of IGF-1 to different DNA motifs in solution were measured by using fluorescence spectroscopy, Surface Plasmon Resonance (SPR), and force-induced remnant magnetization (FIRM). The effects of IGF-1 on the formation and stability of G-quadruplex structures were evaluated by circular dichroism (CD) and melting fluorescence resonance energy transfer (FRET) spectroscopy. The influence of quadruplex-specific ligands on the binding of G-quadruplexes with IGF-1 was determined by FIRM. Results IGF-1 shows a binding specificity for G-quadruplex structures, especially the G-quadruplex structure with a parallel topology. The quadruplex-specific ligands TMPyP4 and PDS (Pyridostatin) can inhibit the interaction between G-quadruplexes and proteins. Conclusions IGF-1 is demonstrated to selectively bind with G-quadruplex structures. The use of quadruplex-interactive ligands could modulate the binding of IGF-1 to G-quadruplexes. General significance This study provides us with a new perspective to understand the possible physiological relationship between IGF-1 and G-quadruplexes and also conveys a strategy to regulate the interaction between G-quadruplex DNA and proteins.

Chirality at a supramolecular level is currently attracting great attention attributed to rapid developments in supramolecular chemistry. Herein, we report a new type of chiral self-assembly based on the cyanine dye MTC. The chiral H-aggregates of MTC could form spontaneously from achiral J-aggregates, and could return back to achiral J-aggregates in high concentration on increasing the solution temperature.

A supramolecular platform prototype for implementing resettable encoding functions was designed, which could be configured into a series of encoders, from 4-to-2 to 7-to-3, and even 14-to-4 ECs.

In this work, a novel and general comparator was constructed based on cascaded strand displacement reactions and DNA hybridization and its potential in intelligently weighing the quantitative predominance of two targets was explored in a complex biological matrix, which not only enriches the information processing mode of DNA computation but also provides an instructive way to deal with quantitative analyzing tasks in further DNA-based logic sensors.

Mechanical biosensors can be used to quantitatively explore DNA-protein binding mechanisms by detecting targets at low concentrations or measuring force in single-molecule force spectroscopy. However, restrictions in single-molecule manipulation and labelling protocols have hindered the application for bulk analysis of label-free protein detection. Here, we present the integration of molecular force measurement and finely tunable detection of label-free proteins into one mechanical sensor. Regulatory-sequence force spectroscopy was obtained to investigate the binding force of DNA G-quadruplexes (GQ) and label-free protein. The dual control of regulatory sequences and mechanical forces induces the structure switching from DNA duplex to GQ/protein complex. It exhibits a synergistic effect, enabling the rational fine-tuning of the dynamic range for biosensing protein concentrations over eight orders of magnitude. Furthermore, this method was exploited to estimate the stability of the human telomeric DNA GQ by Ku protein and ligand methylpyridostatin. The results revealed that human telomeric GQ has two different binding sites for Ku protein and ligand. Force spectroscopy integrating label-free force measurement and tunable target detection holds great promise for use in biosensing, drug screening, targeted therapies, DNA nanotechnology, and fields in which GQ are of rapidly increasing importance.

Monitoring autophagy can provide valuable insights into understanding human pathological mechanisms, developing novel drugs, and exploring autophagy control approaches. Here, we proposed a new strategy to specifically monitor autophagy by lighting up the G-quadruplex structures entering autolysosomes. Based on this strategy, we designed a small-molecule fluorescent probe for autophagy imaging. This work not only opens up a new way for developing autophagy probes, but also provides an effective tool for autophagy research.