Principle and application of self-transcribing active regulatory region sequencing in enhancer discovery research.

Self-transcribing active regulatory region sequencing (STARR-seq) is a high-throughput sequencing method capable of simultaneously discovering and validating all enhancers within the genome. In this method, candidate sequences are inserted into plasmid vectors and electroporated into cells. Acting as both enhancers and target genes, the self-transcription of these sequences will also be enhanced by themselves. By sequencing the transcriptome and comparing the results with the non-inserted control, the locations and activity of enhancers can be determined. In traditional enhancer discovery strategies, the chromatin open regions and transcription active regions were sequenced and predicted as enhancers. However, the activity of these putative enhancers could only be validated one by one without a high-throughput method. STARR-seq solved this limitation, allowing simultaneous enhancers discovery and activity validation in a high-throughput manner. Since the introduction of STARR-seq, it has been widely used to discover enhancers and validate enhancer activity in a number of organisms and cells. In this review, we present the traditional enhancer prediction methods and the basic principles, development history, specific applications of STARR-seq, and its future prospects, aiming to provide a reference for researchers in related fields conducting enhancer studies.

Multiple-stimuli fluorescent responsive metallo-organic helicated cage arising from monomer and excimer emission.

Effectively regulating monomer and excimer emission in a singular supramolecular luminous platform is challenging due to high difficulty of precise control over its aggregation and dispersion behavior when subjected to external stimuli. Here, we show a metallo-cage (MTH) featuring a triple helical motif that displays a unique dual emission. It arises from both intramolecular monomer and intermolecular excimer, respectively. The distorted molecular conformation and the staggered stacking mode of MTH excimer are verified through single crystal X-ray diffraction analysis. These structural features facilitate the switch between monomer and excimer emission, which are induced by changes in concentration and temperature. Significantly, adjusting the equilibrium between these two states in MTH enables the production of vibrant white light emission in both solution and solid state. Moreover, when combined with a PMMA (polymethyl methacrylate) substrate, the resulting thin films can serve as straightforward fluorescence thermometer and thermally activated information encryption materials.

Metal-ion-determined geometrical configurations of metallo-cages with different emission properties.

The formation of metallo-cages is affected by a variety of factors such as the ligands, metals, and anions, among which the impact of metals with different binding capacities is particularly important, but has rarely been studied in three-dimensional metallo-cages. Herein, we report the design of truxene-centered terpyridine ligands and the self-assembly of a series of tetrameric metallo-cages. The utilization of metal ions with strong (Zn2+, Fe2+) or weak (Cd2+) binding strength afforded 3D metallo-cages with low symmetry or highly symmetric metallo-tetrahedra, respectively, possessing totally different geometrical configurations. In addition, their photophysical properties and host-guest chemical properties were investigated.

The effectiveness of fluorescence labeling-based assay bundle intervention in the prevention and control of multidrug-resistant organism infection / 中国感染控制杂志

Objective To observe the effectiveness of fluorescence labeling-based assay bundle intervention in the prevention and control of multidrug-resistant organism(MDRO)infection.Methods Patients who were detected MDRO in a hospital from January to December 2022 were selected as the research subjects.MDRO monitoring data and implementation status of prevention and control measures were collected.Fluorescence labeling assay was adopted to monitor the cleaning and disinfection effectiveness of the surrounding object surface of the bed units.Based on the bundled prevention and control measures as well as management mode of the pre-intervention group,the post-intervention group implemented enhanced rectification measures for the problems found by the pre-interven-tion group.Changes in relevant indicators between January-June 2022(before intervention)and July-December 2022(after intervention)were compared.Results There were 136 MDRO-infected patients in the pre-intervention group,208 MDRO strains were detected and 10 healthcare-associated infection(HAI)occurred.There were 128 MDRO-infected patients in the post-intervention group,198 MDRO strains were detected and 9 HAI occurred.Af-ter intervention,the total detection rates of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-re-sistant Acinetobacter baumannii(CRAB),and total MDRO from patients decreased significantly compared to before intervention(all P＜0.05).After intervention,the detection rates of MRSA,carbapenem-resistant Pseudomonas aeruginosa(CRPA),CRAB,and total MDRO from the surrounding object surface were all lower than those before intervention(all P＜0.05).The detection rate of MDRO from surrounding object surface before intervention was 34.52％,which showed a decreased trend after intervention(P＜0.05).The clearance rate of fluorescent labeled markers before intervention was 41.84％,which showed an upward trend after implementing intervention measures(from July to December),and increased to 85.00％at the end of intervention(November-December).The comp-liance rates of issuing isolation medical orders,placing isolation labels,using medical supplies exclusively,and cor-rectly handling medical waste after intervention have all increased compared to before intervention(all P＜0.05).Conclusion Adopting fluorescence labeling-based assay bundle intervention can effectively improve the effectiveness of MDRO infection prevention and control.

Network pharmacology-based study on mechanism of Zhi-Huang-Zhi-Tong powder in rheumatoid arthritis treatment / 中国药理学通报

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

A truncated triangular prism constructed by using imidazole-terpyridine building blocks.

The construction of low-symmetry topological supramolecular structures using bistable building blocks remains challenging. We report an unusual truncated triangular prismatic cage with D3h symmetry using a ligand with both cis- and trans-configurations upon coordination with metal. This work provides new ideas and methods for the future synthesis of low-symmetry topological supramolecules.

Anion-Regulated Hierarchical Self-Assembly and Chiral Induction of Metallo-Tetrahedra.

The precise control over hierarchical self-assembly of superstructures relying on the elaboration of multiple noncovalent interactions between basic building blocks is both elusive and highly desirable. We herein report a terpyridine-based metallo-cage T with a tetrahedral motif and utilized it as an efficient building block for the controlled hierarchical self-assembly of superstructures in response to different halide ions. Initially, the hierarchical superstructure of metallo-cage T adopted a hexagonal close-packed structure. By adding Cl- /Br- or I- , drastically different hierarchical superstructures with highly-tight hexagonal packing or graphite-like packing arrangements, respectively, have been achieved. These unusual halide-ion-triggered hierarchical structural changes resulted in quite distinct intermolecular channels, which provided new insights into the mechanism of three-dimensional supramolecular aggregation and crystal growth based on macromolecular construction. In addition, the chiral induction of the metallo-cage T can be realized with the addition of chiral anions, which stereoselectively generated either PPPP- or MMMM-type enantiomers.

Crystalline Metallo-Organic Cage by Triphenylene-Cored Hexaterpyridine for Fast Iodine Capture.

In recent years, radioactive iodine capture has played an important role in nuclear waste treatment. However, most of the adsorbents possess low economic efficiency and undesirable reutilization in practical application. In this work, a terpyridine-based porous metallo-organic cage was assembled for iodine adsorption. Through synchrotron X-ray analysis, the metallo-cage was found to have a porous hierarchical packing mode with inherent cavity and packing channel. By taking advantage of polycyclic aromatic units and charged ⟨tpy-Zn2+-tpy⟩ (tpy = terpyridine) coordination sites in the structure, this nanocage exhibits an excellent ability to capture iodine in both the gas phase and aqueous medium, and the crystal state of the nanocage shows an ultrafast kinetic process of capturing I2 in aqueous solution within 5 min. The calculated maximum sorption capacities for I2 based on the Langmuir isotherm models are 1731 and 1487 mg g-1 for amorphous and crystalline nanocages, which is noticeably higher than most of the reported iodine sorbent materials in the aqueous phase. This work not only provides a rare example of iodine adsorption by a terpyridyl-based porous cage but also expands the applications of terpyridine coordination systems into iodine capture.

Probing the Origin of Viscosity of Liquid Electrolytes for Lithium Batteries.

Viscosity is an extremely important property for ion transport and wettability of electrolytes. Easy access to viscosity values and a deep understanding of this property remain challenging yet critical to evaluating the electrolyte performance and tailoring electrolyte recipes with targeted properties. We proposed a screened overlapping method to efficiently compute the viscosity of lithium battery electrolytes by molecular dynamics simulations. The origin of electrolyte viscosity was further comprehensively probed. The viscosity of solvents exhibits a positive correlation with the binding energy between molecules, indicating viscosity is directly correlated to intermolecular interactions. Salts in electrolytes enlarge the viscosity significantly with increasing concentrations while diluents serve as the viscosity reducer, which is attributed to the varied binding strength from cation-anion and cation-solvent associations. This work develops an accurate and efficient method for computing the electrolyte viscosity and affords deep insight into viscosity at the molecular level, which exhibits the huge potential to accelerate advanced electrolyte design for next-generation rechargeable batteries.

Coordination-Driven Tetragonal Prismatic Cage and the Investigation on Host-Guest Complexation.

A coordination-driven host has been reported to encapsulate guests by noncovalent interactions. Herein, we present the design and synthesis of a new type of prism combining porphyrin and terpyridine moieties with a long cavity. The prism host can contain bisite or monosite guests through axial coordination binding of porphyrin and aromatic π interactions of terpyridine. The ligands and prismatic complexes were characterized by electrospray ionization mass spectrometry (ESI-MS), TWIM-MS, NMR spectrometry, and single-crystal X-ray diffraction analysis. The guest encapsulation was investigated through ESI-MS, NMR spectrometry, and transient absorption spectroscopy analysis. The binding constant and stability were determined by UV-Vis spectrometry and gradient tandem MS (gMS2) techniques. Based on the prism, a selectively confined condensation reaction was also performed and detected by NMR spectrometry. This study provides a new type of porphyrin- and terpyridine-based host that could be used for the detection of pyridyl- and amine-contained molecules and confined catalysis.

Tpy-Mn(II)-Tpy (Tpy = 2,2':6',2″-terpyridine)-Based Pentagonal Prism for Green Photodriven Oxidation.

In coordination-driven metal-organic cages, the transition metal ions are generally utilized as linkages. Employment of its unique properties with the aim of achieving specific applications still presents great challenges. Herein, we report a decametric metal-organic cage named pentagonal prism (Mn20LC10) based on Tpy-Mn(II)-Tpy connectivity (Tpy = 2,2':6',2″-terpyridine) in which Mn(II) serves as a linker and endows the resulting metal-organic cage with good photosensitivity. In the photooxidation of benzaldehyde, pentagonal prism Mn20LC10 showed a significantly increased level of 1O2 production, the fastest conversion time, good recyclability, and substrate versatility due to its greatly improved intersystem crossing ability. Notably, the abundant active sites of metal pentagonal prism Mn20LC10 enable its photooxidation under solvent-free and daylight conditions. This work provides approaches for the development of inexpensive, green, and low-cost photosensitizer systems.

Effect of Systematic Graded Rewarming Pattern on All-Cause Mortality of Hypothermic Trauma Patients in Different Time Periods / 中国医学科学院学报

Objective To investigate the effect of systematic graded rewarming pattern on all-cause mortality of hypothermic trauma patients in different time periods. Methods A prospective case-control study was carried out for 236 hypothermic trauma patients with modified trauma score<12 in the Emergency Department of the Second Affiliated Hospital of Wenzhou Medical University from January 2020 to December 2021.The patients were randomly assigned into a systematic graded rewarming group (n=118) and a traditional rewarming group (n=118).The main outcome event was all-cause death within 15 days after trauma,and the secondary outcome event was all-cause death within 3,7,and 30 days after trauma. Results Overall,13.98%(33/236) and 14.83%(35/236) of the patients died within 15 and 30 days after trauma,respectively,and the median survival time of all dead patients was 6 (4,10) days.The systematic graded rewarming group had higher temperature after rewarming for 2 h (P=0.001) and larger temperature change after rewarming intervention (P=0.047) than the traditional rewarming group.The all-cause mortality within 15 days (27.3%vs.72.7%,P=0.005) and 30 days (25.7%vs.74.3%,P=0.002) in the systematic graded rewarming group was lower than that in the traditional rewarming group.Kaplan-Meier analysis showed that the survival time of the patients in the systematic graded rewarming group was longer than that in the traditional rewarming group (P=0.003).Multivariate cox regression analysis indicated that systematic graded rewarming was a strong protective factor for survival time after trauma (HR=0.450, P=0.042).Further Logistic regression analysis for the occurrence of all-cause death in each time period showed that the OR of systematic graded rewarming pattern to all-cause death within 15 days and 30 days after trauma were 0.289 and 0.286,respectively,after adjusting the covariates(P=0.008,P=0.005).The temperature after rewarming for 2 h had a negative correlation with all-cause mortality within 30 days after trauma (OR=0.670, P=0.049). Conclusions Systematic graded rewarming is a protective factor for the survival time of patients with traumatic hypothermia and an independent factor affecting the risk of all-cause death within 15 days and 30 days after trauma.The temperature after rewarming for 2 h is expected to be an independent predictor of all-cause mortality of 30 days after trauma in the patients with hypothermia.The systematic graded rewarming pattern could reduce the mortality of hypothermic trauma patients.

A case of poisoning by oral lime sulfur / 中华劳动卫生职业病杂志

Lime sulfur is a common bactericide with strong alkalinity, and is highly corrosive to humans and animals. It is rare for lime sulfur poisoning clinically. This article discusses the clinical manifestations of a patient who was poisoned by oral lime sulfur. After the poisoning, the mucosa of the lips and pharynx broke, fever, and pulmonary inflammation quickly appeared. The pulmonary CT showed slight interstitial changes in both lungs. Through high flow oxygen inhalation, fluid infusion, drainage, maintenance of water and electrolyte balance, protection of important organ functions, and other symptomatic support and treatment, as well as control of blood pressure, blood sugar, maintenance of circulatory function and other targeted measures, the patient's condition gradually improved.

Research Progress of Long Non-coding RNA in Acute Myeloid Leukemia--Review / 中国实验血液学杂志

Long non-coding RNA (lncRNA) is not "transcriptional noise". It can regulate gene expression at pre-transcriptional, post-transcriptional and epigenetic level and participate in the occurrence and development of diseases. A large number of studies have shown that the abnormal expression of lncRNA plays an important role in the occurrence and development of acute myeloid leukemia (AML) and drug resistance. LncRNA can participate in the occurrence, development and drug resistance of AML by acting on target genes and regulating related signal pathways. Detection of its expression has a certain prognostic value. Therefore, this article briefly discusses the research progress of lncRNA in AML, hoping to provide ideas for clinical diagnosis and targeted therapy.

An Imidazole-Based Triangular Macrocycle for Visual Detection of Formaldehyde.

Highly selective detection of formaldehyde utilizing supramolecules has promising applications in both environmental monitoring and biomonitoring areas. Herein we present a new class of imidazole-based, coordination-driven, self-assembled triangular macrocycles with specific recognition of formaldehyde. The visible fluorescence change to the naked eye from yellow to green-yellow occurs via an unusual reversible hydroxymethylation reaction of imidazole, whereas the corresponding imidazole ligands show no fluorescence change. This study provides a new method for efficient formaldehyde detection by utilizing imidazole-based coordination supramolecules.

Supramolecular cuboctahedra with aggregation-induced emission enhancement and external binding ability.

Beyond the AIE (aggregation-induced emission) phenomenon in small molecules, supramolecules with AIE properties have evolved in the AIE family and accelerated the growth of supramolecular application diversity. Inspired by its mechanism, particularly the RIV (restriction of intramolecular vibrations) process, a feasible strategy of constructing an AIE-supramolecular cage based on the oxidation of sulfur atoms and coordination of metals is presented. In contrast to previous strategies that used molecular stacking to limit molecular vibrations, we achieved the desired goal using the synergistic effects of coordination-driven self-assembly and oxidation. Upon assembling with zinc ions, S1 was endowed with a distinct AIE property compared with its ligand L1, while S2 exhibited a remarkable fluorescence enhancement compared to L2. Also, the single cage-sized nanowire structure of supramolecules was obtained via directional electrostatic interactions with multiple anions and rigid-shaped cationic cages. Moreover, the adducts of zinc porphyrin and supramolecules were investigated and characterized by 2D DOSY, ESI-MS, TWIM-MS, UV-vis, and fluorescence spectroscopy. The protocol described here enriches the ongoing research on tunable fluorescence materials and paves the way towards constructing stimuli-responsive luminescent supramolecular cages.

An organic-Ru2+ cluster-initiated dendritic faced metallo-octahedron and its unpredictable photoactivity.

Herein, a novel 3D metal-organic ligand consisting of a folded Ru(II)-connected tetrameric cycle and two sets of 60° juxtaposed bisterpyridine arms was synthesized and its complexation with Zn2+ gave rise to dendritic-faced metallo-octahedron 6. Remarkably, octahedron 6 displayed unexpected photosensitization ability that could produce singlet oxygen (1O2) under white light irradiation.

Aggregation-Induced Emission Metallocuboctahedra for White Light Devices.

Materials for organic light-emitting devices which exhibit superior emission properties in both the solution and solid states with a high fluorescence quantum yield have been extensively sought after. Herein, two metallocages, S1 and S2, were constructed, and both showed typical aggregation-induced emission (AIE) features with intense yellow fluorescence. By adding blue-emissive 9,10-dimethylanthracene, pure white light emission can be produced in the solution of S1 and S2. Furthermore, due to the remarkable AIE feature and good fluorescence quantum yield in the solid state, metallocages are highly emissive in the solid state and can be utilized to coat blue LED bulbs or integrate with blue-emitting chips to obtain white light. This study advances the usage of metallocages as practical solid-state fluorescent materials and provides a fresh perspective on highly emissive AIE materials.

The dynamic metabolic profile of Qi-Yu-San-Long decoction in rat urine using UPLC-QTOF-MSE coupled with a post-targeted screening strategy / 药物分析学报

Qi-Yu-San-Long decoction(QYSLD)is a traditional Chinese medicine that has been clinically used in the treatment of non-small-cell lung cancer(NSCLC)for more than 20 years.However,to date,metabolic-related studies on QYSLD have not been performed.In this study,a post-targeted screening strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight full infor-mation tandem mass spectrometry(UPLC-QTOF-MSE)was developed to identify QYSLD-related xeno-biotics in rat urine.The chemical compound database of QYSLD constituents was established from previous research,and metabolites related to these compounds were predicted in combination with their possible metabolic pathways.The metabolites were identified by extracted ion chromatograms using predicted m/z values as well as retention time,excimer ions,and fragmentation behavior.Overall,85 QYSLD-related xenobiotics(20 prototype compounds and 65 metabolites)were characterized from rat urine.The main metabolic reactions and elimination features of QYSLD included oxidation,reduction,decarboxylation,hydrolysis,demethylation,glucuronidation,sulfation,methylation,deglycosylation,acetylation,and associated combination reactions.Of the identified molecules,14 prototype compounds and 58 metabolites were slowly eliminated,thus accumulating in vivo over an extended period,while five prototypes and two metabolites were present in vivo for a short duration.Furthermore,one pro-totype and five metabolites underwent the process of"appearing-disappearing-reappearing"in vivo.Overall,the metabolic profile and characteristics of QYSLD in rat urine were determined,which is useful in elucidating the active components of the decoction in vivo,thus providing the basis for studying its mechanism of action.

MiR-130a-3p Alleviates Liver Fibrosis by Suppressing HSCs Activation and Skewing Macrophage to Ly6Clo Phenotype.

Emerging evidences have highlighted the crucial role of microRNAs (miRNAs) in the liver cirrhosis, but the relationship between miR-130a-3p and liver cirrhosis is not entirely clear. As we all know, schistosomiasis, as one of the zoonoses, can lead to liver cirrhosis when it advances. In this study, we investigated the biological functions of miR-130a-3p on the liver fibrosis of schistosomiasis in vivo and in vitro. The mice infected with Schistosoma japonicum (S. japonicum) were treated with lentivirus vector (LV)-miR-130a-3p by hydrodynamic injection through the tail vein. Our findings showed significantly decreased expression of miR-130a-3p both in the serum of patients with cirrhosis and in the liver of mice infected with S. japonicum. The results showed that LV-miR-130a-3p could effectively enter into the liver and alleviate liver granulomatous inflammation and collagen deposition. Simultaneously, LV-miR-130a-3p-promoted macrophages presented the Ly6Clo phenotype, concomitant with the decreased expression of the tissue inhibitor of metalloproteinases (TIMP) 1, and increased the expression of matrix metalloproteinase (MMP) 2, which contributed to the dissolution of collagen. Furthermore, overexpression of miR-130a-3p not only inhibited the activation and proliferation of hepatic stellate cells (HSCs) but also induced the apoptosis of HSCs. In addition, we also confirmed that miR-130a-3p enables to bind with mitogen-activated protein kinase (MAPK) 1 and transforming growth factor-beta receptors (TGFBR) 1 and TGFBR2 genes and inhibit the expressions of these genes. Our findings suggested that miR-130a-3p might represent as the potential candidate biomarker and therapeutic target for the prognosis identification and treatment of schistosomiasis liver fibrosis.